Wednesday, February 29, 2012
HCAB Position Statement: Hepatitis C Drug Development and Drug-Drug Interaction Studies...
This HCAB (Hepatitis C Community Advisory Board) position statement was published on 2/28/12 regarding Hepatitis C drug development and drug-drug interaction (DDI) studies. In short, the HCAB would like drug developers to be more proactive in doing DDI studies before the drugs come to market. They admonish Merck specifically for not doing DDI studies with commonly available antiretrovirals and their HCV antiviral drug, boceprevir. Further, they applaud the efforts of Vertex and J&J for doing full due diligence in DDI studies prior to the launch of Telaprevir.
HCAB Position Statement: Hepatitis C Drug Development and Drug-Drug Interaction Studies
February 17, 2012 -- The Hepatitis C Community Advisory Board (HCAB) recognizes the value of more effective and less toxic treatment for hepatitis C virus (HCV). We believe that sponsors can conduct key drug-drug interaction (DDI) studies with direct-acting antivirals (DAAs) and other candidates in development and medications commonly used by people with hepatitis C and those coinfected with HIV/HCV prior to their approval, without delaying development of these important therapies.
DAAs may share metabolic pathways with drugs that are commonly used by populations with a high prevalence of hepatitis C, such as hormonal contraceptives, methadone, buprenorphine, lipid-lowering agents, immunosuppressive drugs, herbal remedies, and commonly prescribed psychiatric medications.
In recognition of the suboptimal efficacy and tolerability of [pegylated interferon] and ribavirin, rapid trajectory of liver disease progression, and increasing mortality from HCV-related complications among HIV/HCV coinfected patients, regulators in the US and the EU encourage sponsors to conduct trials in HIV/HCV coinfected patients prior to approval for HCV monoinfection. Sponsors have already opened, or plan to launch these trials.
The recent discovery of drug-drug interactions between boceprevir and boosted HIV protease inhibitors underscores the importance of DDI studies with DAAs. Although we commend the sponsor, Merck, for opening one of the first coinfection trials with a DAA, we were outraged that Merck chose not to conduct DDIs with commonly used antiretroviral agents prior to launching the trial, and prior to gaining approval for boceprevir. Vertex and Tibotec were able to bring telaprevir [Incivek] to market with a much fuller portfolio of DDI data, although both drugs were developed within the same timeframe.
HCAB asks FDA [the US Food and Drug Administration], EMA [European Medicines Agency] and pharmaceutical companies to work together to minimize potential harm to hepatitis C monoinfected and HIV/HCV coinfected patients from uncharacterized drug-drug interactions. Furthermore, we call upon sponsors to perform DDI studies (as indicated by metabolic profile of their drug or drugs) with DHHS [US Department of Health and Human Services], EACS [European AIDS Clinical Society] and WHO [World Health Organization]-recommended antiretroviral agents for first-line, and treatment-experienced HIV/HCV coinfected people prior to approval, and strongly encourage studies of hormonal contraceptives, methadone, buprenorphine, lipid-lowering agents, immunosuppressive drugs, herbal remedies, and commonly prescribed psychiatric medications.
2/28/12
Source
Hepatitis C Community Advisory Board. HCAB Position Statement: Hepatitis C Drug Development and Drug-Drug Interaction Studies. February 16, 2012.
The Motley Fool comments on "The Hepatitis C Bubble"...
Posted 2/29/12 on The Motley Fool.com. Brian Orelli, PhD comments on investor 'irrational exuberance' within HCV drug developer stocks and urges caution. Having been in the pharma and biopharma industry since '93, I'm in Orelli's camp in erring on the side of fiscally conservative. The major of preclinical drugs - and even drugs in phase II development - never make it to market. That's never more been the case than in Hepatitis C drug development. The 'Phase II graveyard' of compounds that will never see the light of day is huge by any standard.
3 Signs of a Hepatitis C Bubble
By BRIAN ORELLI, PHD, THE MOTLEY FOOL
Posted 9:37PM 02/29/12 Investing
0 CommentsText Size A A A
Gilead Sciences' (NAS: GILD) purchase of Pharmasset and Bristol-Myers Squibb's takeout of Inhibitex threw gasoline on a fire that was already raging.
But higher values in and of themselves don't necessarily mean the indication is in a bubble that's sure to pop. You have to dig a little deeper. Here are three signs the enthusiasm might be getting a little extreme.
Preclinical fever
BioCryst Pharmaceuticals (NAS: BCRX) rose 12% in one day earlier this month after announcing data on its hep C drug, BCX5191. That's not weird -- drugmakers are supposed to go up when they release positive data.
But BCX5191 hasn't even made it into the clinic yet.
Early-stage success does tend to be a better predictor of approvability for hepatitis C drugs than it is for drugs treating other indications, but I'd be very cautious reading too much into the results, especially considering how many drugs are already in the clinic.
Acquisition exuberance
BioLineRx shares more than doubled at one point last month on 675 times the volume the day before apparently because the company licensed a hepatitis C drug BL-8020 from a privately held French biotech, Genoscience.
Did it get such a good deal that the company was instantly worth twice as much? Who knows? The terms of the deal weren't disclosed. It couldn't have been worth that much, though, considering BL-8020 hasn't made it to the clinic either. Then again, see above.
My guess is that investors jumped into BioLineRx because they think having a hepatitis C drug makes the biotech a takeout target. And considering the premiums we've seen thus far, the rewards could be plentiful if they continue.
Trading in tandem
Speaking of acquisition, Idenix Pharmaceuticals (NAS: IDIX) and Achillion Pharmaceuticals (NAS: ACHN) have been long-rumored acquisition targets, especially as Pharmasset and Inhibitex were taken out.
The drugmakers have traded virtually in tandem as investors have treated them identically, expecting both to be the next M&A victor.
But it's not like they have the same pipelines. There's no reason to think they have the same risk-reward profile. Losing perspective of the underlying asset is a sure sign of a bubble.
But will it pop?
There's no doubt there's a bubble: Valuations on hepatitis c drugs are much higher than any other drug. I'm unaware of any biotech without a drug on the market that has a valuation above $11 billion, the price that Gilead paid for Pharmasset.
But whether the bubble will pop is harder to know. I tend to think that investors and companies snapping up the assets will eventually come to the realization that the rewards at these insane levels don't justify the risks.
But it doesn't have to go down like that, I guess. There are a lot of patients infected with the virus who may not be identified and still more who know they're infected and choose to wait for the next generation of medications. And the cost of not ridding the patients of the virus is fairly high - hepatitis C is a leading cause of liver transplants -- so hep C drugmakers can justify fairly high prices.
The drugs could succeed in the clinic and patients could be identified, resulting in billions of dollars in sales and a justification of the high prices.
But even in that rosy picture, not every drug is going to work. And even if it's approved, there's no guarantee it'll actually get prescribed over the rivals. Just look at the competition between Vertex Pharmaceuticals (NAS: VRTX) and Merck, whose drugs launched at nearly the same time, but Incivek has sales five times higher than Victrelis.
Even if the entire hep C drug space doesn't pop, someone is going to be left holding the bag. Be careful out there.
Tuesday, February 28, 2012
In 2015, Gilead's GS-7977 Plus Ribavirin Will Earn Decision Resources' Proprietary Clinical Gold Standard Status for the Treatment of Non-Responder Patients with Hepatitis C Virus...
Press release posted 2/28/12 on Marketwatch.com. Although their output is always of exceptional high-quality, Decision Resources' ability to pick a 'whip-your-head-right-around, spill-your-coffee-and-read-at-all-costs' attention-grabbing headline in hopes that you'll buy their product, is unprecedented in the market analysis marketplace. That's the type of unexpurgated crassness we'd like to see more of. You have to love them. Apparently, the oracles at DR have already decided that they will award GS-7977 plus RBV the "Decision Resources' Proprietary Clinical Gold Standard" for treatment of non-responders in 2015. That's some unshakable confidence, let's hope they're right because no one is going to let them forget this press release. Despite the puffery, some interesting analysis is to be gleaned from this press release. They've obviously been doing some serious homework. DR expects that "the overall HCV drug market will experience significant growth, expanding from almost $1.7 billion in 2010 to $14.4 billion in 2015 in the United States, France, Germany, Italy, Spain, the United Kingdom and Japan. Thereafter, the market will decrease to $11.2 billion in 2020, owing to a decline in the size of the treatment-eligible population due to declining prevalence and effective new regimens." Compelling reason enough on why the HCV drug development marketplace is red hot at the moment.
In 2015, Gilead's GS-7977 Plus Ribavirin Will Earn Decision Resources' Proprietary Clinical Gold Standard Status for the Treatment of Non-Responder Patients with Hepatitis C Virus
* GS-7977 Plus Ribavirin Will Displace the Current Proprietary Clinical Gold Standard, Telaprevir in Combination with Peg-IFNa/Ribavirin, According to Findings from Decision Resources
BURLINGTON, Mass., Feb 28, 2012 (BUSINESS WIRE) -- Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that, based on clinical data and the opinions of interviewed thought leaders, telaprevir (Vertex's Incivek, Johnson & Johnson's Incivo) in combination with peg-IFNa (Roche's Pegasys or Merck's Victrelis) and ribavirin (Roche's Copegus; Merck's Rebetol; generics) has earned Decision Resources' proprietary clinical gold standard status for the treatment of non-responder patients with hepatitis C virus (HCV). Owing to its competitive advantages in safety and tolerability as well as delivery, the interferon-free combination of Gilead's GS-7977 (formerly PSI-7977) plus ribavirin will displace telaprevir plus peg-IFNa/ribavirin and earn proprietary clinical gold standard status for HCV non-responders in 2015, following its launch for the indication in 2014 in the United States.
Decision Resources' analysis of the hepatitis C virus drug market also finds that surveyed U.S. gastroenterologists and managed care organization (MCO) pharmacy directors agree that the percentage of genotype-1 null responders achieving sustained virologic response is one of the attributes that most influences their decisions regarding prescribing and formulary status determinations, respectively, in HCV non-responders.
"Clinical data and the opinions of interviewed thought leaders indicate that several emerging regimens utilizing novel, HCV-specific direct-acting antivirals have advantages over sales-leading telaprevir plus peg-IFNa/ribavirin on this attribute," said Decision Resources Analyst Seamus Levine-Wilkinson, Ph.D.
According to insights from surveyed U.S. gastroenterologists and MCO pharmacy directors, the absence of interferon-free treatment options for HCV is one of the greatest unmet needs in HCV. Clinical data and the opinions of interviewed thought leaders indicate that GS-7977 has demonstrated the potential to significantly fulfill this unmet need.
The findings also reveal that surveyed U.S. gastroenterologists indicate that they would prescribe the quadruple regimen of Bristol-Myers Squibb's NS5A inhibitor daclatasvir (BMS-790052) plus Bristol-Myers Squibb's protease inhibitor asunaprevir (BMS-650032) plus peg-IFNa/ribavirin to 41 percent of their HCV non-responder patients. Decision Resources' forecast for this quadruple regimen is more conservative due to anticipated reimbursement restrictions, positioning in later lines of therapy, competition from IFN-free regimens and competition asunaprevir will face from other protease inhibitors.
The launch of novel HCV-specific agents will increase the size of the drug-treated population mainly as a result of re-treatment of prior non-responders as well as increased referral and drug treatment rates. The overall HCV drug market will experience significant growth, expanding from almost $1.7 billion in 2010 to $14.4 billion in 2015 in the United States, France, Germany, Italy, Spain, the United Kingdom and Japan. Thereafter, the market will decrease to $11.2 billion in 2020, owing to a decline in the size of the treatment-eligible population due to declining prevalence and effective new regimens.
Decision Resources' Robust Market Forecast and Opportunities Analysis
Decision Resources provides a comprehensive view of what is happening in a specific drug market now and in the decade ahead. The research includes analysis of the unmet need and near-term drug development opportunities that exist within a drug market powered by primary research from physicians and payers. The robust market forecast and opportunities analysis is comprised of the Pharmacor 2012 advisory service and the DecisionBase 2012 report series.
About Decision Resources
Decision Resources ( www.decisionresources.com ) is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources Group company.
About Decision Resources Group
Decision Resources Group is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources Group at www.DecisionResourcesGroup.com .
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SOURCE: Decision Resources
Decision Resources
Christopher Comfort, 781-993-2597
ccomfort@dresources.com
Monday, February 27, 2012
Wall Street Journal - "Medivir Vies For Spot In Narrow Hepatitis C Market"
Posted 2/27/12 in the Wall Street Journal: Now here's a corporate leader with some confidence, bordering on cockiness, which, arguably is what coporate leaders should have copious amounts of. Even if it's bluster. Medivir Executive Vice-President of Corporate Affairs Rein Piir tells Dow Jones that "there is nothing in development that's better than TMC435, which is currently in global Phase III trials and which Medivir expects to launch by the end of next year." This puts TMC435, if he's right, to be potentially the first 2nd generation DAA to hit the market, at least ex-US.
By Simon Varcoe
Of DOW JONES NEWSWIRES
LONDON (Dow Jones)--Hepatitis C, a harrowing infection that leads to the inflammation of the liver, is a virus of pandemic size that has attracted the attention of some of the world's biggest drug makers.
But Sweden's small biotech Medivir AB (MVIR-B.SK) says it intends to be a major player in treating the disease, and predicts the market will ultimately have room for just four or five products.
"It is simply a question of which drug will have the biggest share of the market", Medivir's executive vice-president of corporate affairs Rein Piir told Dow Jones Newswires in an interview.
And in protease inhibitor TMC435, Piir believes Medivir has found its winner.
Piir says there is nothing in development that's better than TMC435, which is currently in global Phase III trials and which Medivir expects to launch by the end of next year.
Danske Banke analyst Hans Jeppsson agrees.
Jeppsson regards TMC435 as being the best-in-class protease inhibitor, which prevents viral replication by inhibiting the activity of protease enzymes. Final judgment will need to await results from two combination trials the drug is currently undergoing, he adds.
Around 170 million people are infected worldwide with Hepatitis C, a disease that can be transmitted sexually, through shared needles or through infected blood transfusions.
Thousands of people in Japan were infected with Hepatitis C between the 1970s and 1990s due to tainted blood clotting agents and the country remains one of the most hepatitis C-dense in the world. Due to the high numbers of hepatitis C sufferers in Japan, the country is "as important commercially" to Medivir as Europe, Piir says.
Other countries with a high prevalence of Hepatitis C include Egypt, where around 20% of blood donors are anti-HCV positive, and areas of Italy.
Medivir's Piir believes that the future treatment of Hepatitis C will involve a combination of protease inhibitors; inhibitors of nucleotides, which are molecules that, when joined together, make up the structural units of RNA and DNA; and inhibitors of NS5A, a non structural viral protein found in Hepatitis C.
NS5A inhibitors currently in development include Bristol-Myers Squibb's (BMY) BMS790052, and Gilead Sciences Inc's (GILD) GS-7977. However, Gilead recently reported that a majority of patients in a clinical trial of GS-7977 had experienced a relapse in their disease after being treated with the product, raising questions about the market potential of the drug and the wider class of NS5A inhibitors.
A protease inhibitor currently used to treat HCV genotype 1 infection, the most common and hardest-to-treat type of Hepatitis C is Vertex Pharmaceuticals' (VRTX) and Johnson & Johnson's (JNJ) telaprevir, though, unlike TMC435, it must be administered in combination with pegylated interferon alpha and the antiviral drug ribavirin. Its safety profile has also been criticized, whereas TMC435 has to-date been generally safe and well tolerated, according to Medivir.
The Swedish biotech floated on the Nasdaq OMX Stockholm index in 1996 and currently has a market capitalization of around SEK2.1 billion ($320.2 million).
-By Simon Varcoe, Dow Jones Newswires; +44-20-7842-9449; simon.varcoe@dowjones.com
Thursday, February 23, 2012
Vertex Pharmaceuticals posts ZENITH all oral combo interim results...
Posted 2/23/12 on Fierce Biotech - Interim results from Vertex's ZENITH
trial, looking at an all-oral combo of Telaprevir, non-nuc VX-222 and Ribavirin for 12 weeks. Eleven of 46 Tx-naive G1 patients met the week 2 and 8
criteria of having undectectable virus and were eligible to stop all treatment at
week 12. Nine of the 11 achieved SVR4,
with equal viral kinetics for both G1a and G1b.
VRTX is pushing this combo ahead into Phase IIb studies, with a hopeful
eye on possible NDA filing in late 2014 .
Vertex vows to race ahead with interferon-free combo for hep C
February 23, 2012 — 10:50am ET | By John Carroll
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Determined to try and keep pace with rival next-gen hepatitis C treatments in the pipeline, Vertex ($VRTX) today unveiled a slate of somewhat positive interim midstage results for an all-oral combo regimen that includes its game-changing drug Incivek along with the experimental VX-222--its non-nucleoside polymerase inhibitor--and ribavirin.
The standard goal for new hepatitis C drugs is the sustained elimination of all signs of the virus by week 12, allowing patients to stop treatment, though developers are aiming for the fastest cure rates possible. Vertex noted that 11 of 46 treatment naïve patients with the genotype 1a and 1b virus met the criteria of having "undetectable hepatitis C virus at weeks two and eight of treatment and were therefore eligible to stop all treatment at 12 weeks. Nine of these 11 patients achieved SVR4 (undetectable hepatitis C virus four weeks after the end of all treatment)." Data showed that viral loads were below the "lower limit of quantification" for 83% of the patients at week 12.
Based on the data, Vertex says it will push ahead with a Phase IIb study of the interferon-free combo, anticipating that investigators can nail late-stage data for an NDA to the FDA as early as late 2014--keeping on an ambitious development schedule.
"Our ultimate goal is to develop well-tolerated, interferon-free treatment regimens with high viral cure rates and short treatment durations for people with hepatitis C," said Vertex CSO Peter Mueller. "We believe we're well-positioned to achieve this goal by exploring various combinations within our portfolio that includes Incivek, VX-222 and two structurally-distinct nucleotide polymerase inhibitors."
Those two nucleotide polymerase inhibitors he referred to are ALS-2200 and ALS-2158, which were licensed in from Alios and perhaps represent Vertex's best shot at gaining an edge over treatments being studied at rival companies. Vertex said today that it has begun the first 7-day viral kinetic studies of ALS-2200 and ALS-2158 in people with genotype 1 hepatitis C. Safety and viral kinetic data from these studies are expected in the second quarter of 2012, enabling the launch of midstage studies in the second half of 2012.
Vertex vows to race ahead with interferon-free combo for hep C
February 23, 2012 — 10:50am ET | By John Carroll
Free newsletter via e-mail
Determined to try and keep pace with rival next-gen hepatitis C treatments in the pipeline, Vertex ($VRTX) today unveiled a slate of somewhat positive interim midstage results for an all-oral combo regimen that includes its game-changing drug Incivek along with the experimental VX-222--its non-nucleoside polymerase inhibitor--and ribavirin.
The standard goal for new hepatitis C drugs is the sustained elimination of all signs of the virus by week 12, allowing patients to stop treatment, though developers are aiming for the fastest cure rates possible. Vertex noted that 11 of 46 treatment naïve patients with the genotype 1a and 1b virus met the criteria of having "undetectable hepatitis C virus at weeks two and eight of treatment and were therefore eligible to stop all treatment at 12 weeks. Nine of these 11 patients achieved SVR4 (undetectable hepatitis C virus four weeks after the end of all treatment)." Data showed that viral loads were below the "lower limit of quantification" for 83% of the patients at week 12.
Based on the data, Vertex says it will push ahead with a Phase IIb study of the interferon-free combo, anticipating that investigators can nail late-stage data for an NDA to the FDA as early as late 2014--keeping on an ambitious development schedule.
"Our ultimate goal is to develop well-tolerated, interferon-free treatment regimens with high viral cure rates and short treatment durations for people with hepatitis C," said Vertex CSO Peter Mueller. "We believe we're well-positioned to achieve this goal by exploring various combinations within our portfolio that includes Incivek, VX-222 and two structurally-distinct nucleotide polymerase inhibitors."
Those two nucleotide polymerase inhibitors he referred to are ALS-2200 and ALS-2158, which were licensed in from Alios and perhaps represent Vertex's best shot at gaining an edge over treatments being studied at rival companies. Vertex said today that it has begun the first 7-day viral kinetic studies of ALS-2200 and ALS-2158 in people with genotype 1 hepatitis C. Safety and viral kinetic data from these studies are expected in the second quarter of 2012, enabling the launch of midstage studies in the second half of 2012.
Wednesday, February 22, 2012
APASL: Alisporivir Resistance/CC/TT Gt Phase 2b Study...
Lovingly swiped from the great NATAP.org newsletter - a report from intrepid advocate/reporter Jules Levin from the Asian Pacific Association for the Study of the Liver conference on Alisporivir (formerly known as DEBIO-025) resistance analysis from the ESSENTIAL study. Alisporivir is a Cyclophilin Inhibitor under development by Novartis. I thought that this was an interesting poster, as viral resistance to the DAAs is somewhat uncharted territory/conveniently overlooked depending on your particular position. A solid knowledge base regarding HCV resistance will be essential to HCV drug developers in regards to successfully sequencing therapy to achieve and SVR in patients that have failed previous therapy. Cyclophilin Inhibitors, long the unsexy underdog in HCV drug developmen,t may have an important role in possible interferon-free combinations. With Alisporivir's polymerase and protease inhibitor brethren, genotypic resistance is the primary driver to viral resistance, thus breakthrough and relapse. With the Cyclophilin Inhibitor class, it appears that a combination of suboptimal drug exposure, frequent PEG/RBV dose reduction or host factors seem to be the reason for the rare breakthrough seen in this particular study. This harkens back to HIV Antiretroviral 101 - drug exposure and adherence - and not just to Alisporivir, but to PEG/RBG as well - is critical. This thinking should be applied to the current paradigm of DAA therapy with Boceprevir and Telaprevir as well to ensure successful outcomes.
Subject: NATAP/APASL: Alisporivir Resistance/CC/TT Gt Phase 2b StudyAlisporivir, a Host-targeting Antiviral, in Combination with Peg-IFNα2a and Ribavirin Results in Superior SVR and No Viral Breakthrough in HCV Genotype 1 Treatment-naïve Patients of IL28B CC Genotype: Results from the Phase IIb ESSENTIAL Study- see attached full poster reportReported by Jules Levin22nd Conference of the Asian Pacific Association for the Study of the Liver • February 16-19, 2012 • Taipei, TaiwanBin Li,1 Joke Snoeck,2 Yanhua Tang,1 Christopher T. Jones,1 Weibin Bao,3 Jing Yu,1 Yali Li,1 Anne-Mieke Vandamme,2 Gregoire Vuagniaux,4 Kai Lin11Novartis Institutes for BioMedical Research, Inc, Cambridge MA, USA; 2Rega Institute and KU Leuven, Leuven, Belgium; 3Novartis Pharmaceuticals, East Hanover NJ, USA; 4Debiopharm SA, Lausanne, Switzerland
SUMMARY• Alisporivir (ALV)/Peg-IFN2α/RBV treatment achieved 100% SVR in patients of IL28B CC genotype in the RGT and ALV/48wks arms• Nearly 70% of patients of CC genotype cleared virus within 4 wks of treatment and qualified for shortened therapy• No VB was observed in any patient of CC genotype while on full dose of ALV treatment• The rare occurrence of VB (patients of CT or TT genotype) was associated with frequent Peg/RBV dose adjustment or treatment stoppage, as well as suboptimal drug exposure• Previously reported D320E (NS5A domain II) mutation emerged at the time of breakthrough in one patient (1/215), although phenotypic analysis revealed only ~3-fold change in susceptibility to ALV for clinical isolates harboring D320E• Clinical data demonstrated virus harboring D320E was susceptible to ALV when exposed to sufficient drug level• Unlike DAAs, VB in ALV triple therapy was not primarily driven by genotypic resistance; a combination o f suboptimal drug exposure, host factors and low-level of genotypic resistance may all contribute to VB• Consistent with in vitro cross-resistance data, patients with preexisting resistance mutations to DAAs remained susceptible to ALV triple therapy, supporting combining ALV with DAA in IFN-free combination to treat HCV“No difference observed between GT1a and 1b: 1/43 GT1a and 5/172 GT1b patients had VB while on full dose of ALV”
Tuesday, February 21, 2012
Novartis Pays Enanta $34M Up Front for Worldwide Rights to HCV NS5A Inhibitors
From Genetic Engineering & Biotechnology News, posted 2/21/12: Novartis entered a deal with Watertown, MA's Enanta Pharmaceuticals for the worldwide rights to develop and commercialize Enanta's lead HCV NS5A candidate EDP-239 and further compounds targeting NS5A target. Both companies kept it rather low profile in this day and age of fast-flying press releases in the HCV development space. Stay tuned for further details.
Novartis Pays Enanta $34M Up Front for Worldwide Rights to HCV NS5A Inhibitors
Novartis is paying Enanta Pharmaceuticals $34 million up front for worldwide rights to develop and commercialize the latter’s lead HCV NS5A inhibitor candidate, EDP-239. Enanta could receive up to $406 million in clinical, regulatory, and commercial milestones plus tiered double-digit royalties on sales and retains co-detail rights in the U.S.
Under terms of the deal Novartis will shoulder all costs associated with the development, manufacture, and commercialization of EDP-239. It will also provide Enanta with funding for the discovery of additional compounds targeting NS5A.
NS5A is a nonstructural viral protein that is critical for viral replication. Enanta says its EDP-239 inhibitor has demonstrated high potency against multiple HCV genotypes in vitro, and its preclinical pharmacokinetic profile supports the potential for once-daily dosing in humans.
Anti-infectives specialist Enanta is developing HCV protease, polymerase, and cyclophilin-based inhibitors and has generated a class of macrolide antibiotics, called bicyclolides, which it claims can overcome bacterial resistance. The firm teamed up with Abbott in 2006 to develop and commercialize HCV HS3 and NS3/4A protease inhibitors through a $57 million cash and equity investment deal that also gives its partner access to drug discovery capabilities in the field of HCV NS3 and NS3/4A protease inhibitor field. Enanta’s HCV polymerase and cyclophilin programs are ongoing in house.
Enanta’s bicyclolide program is focused on the development of oral broad-spectrum candidates against community MRSA and community-acquired respiratory tract infections caused by pathogens including S. pneumonia, S. aureus, S. pyogenes, and H. influenza as well as a hospital-acquired MRSA and VRE
G&E News: Patients’ Expectations About New HCV Direct-Acting Antivirals Often Unrealistic...
Lovingly pinched on 2/21/12 from Gastroenterology & Endoscopy News. Ms. Frangou interviews three well-regarded giants of Hepatology, Andrew Muir, Raymond Chung and Gary Davis about the disconnects that often occur between patient expectations with triple therapy and reality. An excellent article about the realities of treatment, definitely worth the read. It would be great to see more attention paid to the mid-level practitioners who are really doing the majority of heavy lifting in this disease state. Getting their perspective on treating patients would be hugely valuable, as they are the ones that often manage the patients day-to-day, manage the patients support systems and often have the frustrating role of pushing through the prior authorizations to get these drugs for patients in the first place. They are definitely the heroes on the front lines fighting this disease.
Hepatology in Focus
ISSUE: FEBRUARY 2012 | VOLUME: 63
Patients’ Expectations About New HCV Direct-Acting Antivirals Often Unrealistic
Careful Patient Selection, Education Is Key for Success
by Christina Frangou
San Francisco—Soon after the FDA approved two direct-acting antiviral agents (DAAs) last spring for treating infection with hepatitis C virus (HCV), a 57-year-old black man came to see gastroenterologist Andrew Muir, MD.
The man had been diagnosed with hepatitis C in 2001. A liver biopsy one year later revealed he had stage II fibrosis. At the time, the patient declined treatment, saying the duration was too long and offered too few benefits.
But recently, he came back to Dr. Muir wanting to try a new protease inhibitor. Based on his reading, the man believed he could avoid interferon (IFN) and ribavirin (RBV), take a protease inhibitor as monotherapy for 24 weeks and expect a 75% chance of achieving a sustained virologic response (SVR).
Unfortunately, the patient’s expectations were unrealistic on all counts. The new protease inhibitor can only be given in conjunction with IFN and RBV, and the treatment duration varies. For blacks, therapy usually lasts a full 48 weeks, and in clinical trials, only 30% of black patients achieved an SVR with 28 weeks of therapy. Moreover, among black patients in the Phase III trials, SVR rates fell short of the 75% that the patient expected, and in treatment-naive blacks, only 62% receiving telaprevir and 53% on boceprevir achieved an SVR.
Educate To Encourage Adherence
Unrealistic expectations are common among patients with HCV infection who, after years of waiting for better therapies, are eager to try treatment with the new DAAs, said Dr. Muir. The DAAs on the market today are complex, with varied stoppage rules, monitoring points and some serious adverse events and drug–drug interactions.
“This is a real problem for clinicians. There’s tremendous excitement about these new therapies, but oftentimes, patients’ expectations are not in line with what these drugs can deliver,” said Dr. Muir, clinical director of hepatology at Duke University Medical Center, Durham, N.C.
In a presentation at The Liver Meeting 2011, Dr. Muir stressed that clinicians need to take time to carefully prepare patients for DAA therapy. Physicians must have clear, detailed discussions with their patients before and throughout treatment to optimize the benefits of DAA therapy, he said.
“The major challenges are preparing patients for the rigors of therapy, checking in frequently to make decisions about the duration of treatment and managing any issues as the patient goes along,” said Dr. Muir.
When patients come into the office considering treatment with DAAs, the first step is to clarify their expectations, said Dr. Muir. Patients need to learn the reality about DAAs if they want treatment to succeed.
Dr. Muir outlines for patients the complex prescribing rules, the contraindications, the lifestyle changes and duration of treatment with DAAs. The lifestyle changes can be significant, he cautions patients. Both telaprevir and boceprevir must be taken three times a day, or once every eight hours, and always with a meal. Dr. Muir then asks if the patient still wants treatment when these things are taken into account.
“That’s no small feat. Patients must adhere to that regimen because lapses in the concentration of telaprevir and boceprevir have historically been the risk period for breakthrough variants on therapy,” said Raymond Chung, MD, chief of hepatology and vice-chief of gastroenterology at Massachusetts General Hospital, Boston. Many of Dr. Chung’s patients limit or reschedule their work hours while on DAA therapy to help with adherence.
The key to getting patients through DAA treatment successfully is to select patients carefully and prepare them assiduously, said Gary L. Davis, MD, director of general and transplant hepatology at Baylor University Medical Center, Dallas. “This means that any issues that might impact compliance, tolerance and drug access should be dealt with before treatment starts. Educating the patient is essential. Patients and their support person need to clearly understand the importance of dosing compliance, lab monitoring and treatment stopping rules/end points.”
The treatment care team then needs to remain in close contact with the patient throughout treatment to reinforce adherence and offer feedback on their process, he added. At Dr. Chung’s office at Massachusetts General Hospital, one nurse practitioner has been assigned full-time to managing patients on DAAs. She works with them on everything from managing possible reactions like rash and anemia to helping them set up a daily schedule for taking the medications.
“We have 50 to 100 patients in varying stages of DAA treatment,” said Dr. Chung. “Every one of these patients is coming in for frequent visits—weekly in the beginning—and they are very much in need of monitoring, not just for adverse events like rash but also for fatigue and their ability to carry out work.”
Begin With a Thorough History
Before patients start the new therapies, gastroenterologists and hepatologists should consider getting a liver biopsy to help guide treatment, said Dr. Muir. Physicians also should confirm a patient’s history of treatment for HCV. If patients were previously on antiviral therapies, physicians need to find out as much as they can about that experience.
“You must ask whether we can improve upon previous treatment,” said Dr. Muir. “Were there adverse events with treatments? Were there dose reductions? If so, were they appropriate? How was patient adherence to medications? Did they use alcohol?”
Based on that information, physicians should outline the likelihood of each individual patient achieving an SVR, he said. The key predictors of SVR are whether patients are treatment-naive or treatment-experienced, whether they have cirrhosis and their race. Another important issue for patients is treatment duration. Duration will vary depending on each patient’s characteristics. “It’s important to speak with every patient about their likelihood of a shorter duration of treatment,” said Dr. Muir.
The American Association for the Study of Liver Diseases recommends 48 weeks of treatment for all patients with cirrhosis, as fewer patients with cirrhosis were included in the clinical trials that led to approval of the new drugs. Among those included, virologic response levels were lower than for patients without cirrhosis. For treatment-naive patients, 46% of non-black and 29% of black patients in the boceprevir SPRINT-2 (Serine Protease Inhibitor Therapy 2) trial achieved undetectable levels of HCV by 28 weeks, making them eligible for the shortened course of treatment (Poordad F et al. N Engl J Med 2011;364:1195-1206). In the telaprevir trial, 58% of patients had an early rapid virologic response (Jacobson IM et al. N Engl J Med 2011;364:2405-2416).
Patients’ interleukin-28B (IL28B) genotype also affects the expected duration of treatment. For both boceprevir and telaprevir, patients with the IL28B CC genotype are most likely to attain an early virologic response, more likely to receive a shortened course of therapy and more likely to have an SVR, according to studies presented at last year’s annual meeting of the European Association for the Study of the Liver.
Follow Through: Monitor for Response, Resistance, Reactions, Interactions
When the new HCV drugs were first approved, physicians’ offices reported some trouble getting approval from third-party payers for the full course of treatment, said Dr. Chung. His office had to provide documentation of successful early virologic response to get the go-ahead from payers to approve continuation of treatment with a protease inhibitor.
“You can imagine that if any gaps occur in the virologic tests or their reporting, this could lead to interruption of protease inhibitor therapy. It’s been a real challenge,” he said.
Experts recommend following patients very carefully over the course of treatment, monitoring any virologic breakthroughs or adverse reactions to the medications, particularly rash and anemia. Dr. Chung sees patients after the first, second and fourth week of therapy, and every four weeks thereafter if patients are having an uneventful course. Treatment monitoring is essential to prevent unwarranted continuation of treatment in patients when a breakthrough has occurred, he said.
“That would signal the emergence of resistant variants. Upon discovery, it would be paramount to discontinue the entire regimen to prevent selection of additional resistance mutations,” he said.
Equally important is the need to monitor patients closely for adverse reactions and drug–drug interactions. As IFN and RBV remain the backbone of this HCV regimen, the same contraindications exist as with standard dual therapy: decompensated cirrhosis, renal insufficiency, advanced cardiac/pulmonary disease, active depression, severe mental illness, anemia/neutropenia/thrombocytopenia and noncompliance.
Additionally, there are important drug–drug interactions with boceprevir and telaprevir. Both DAAs inhibit the CYP3A4/5 enzyme. Drugs metabolized by CYP3A4/5 may have increased effect in the presence of boceprevir or telaprevir. The DAAs themselves are metabolized by this cytochrome. As a result, other drugs that induce or inhibit CYP3A4/5 could affect HCV levels.
“Planning is key to deal with drug–drug interactions,” said Dr. Muir. It’s very important to do a risk–benefit analysis of treatment with boceprevir and telaprevir, taking into account patients’ comorbidities, he added.
It is important to review all drugs that the patient is taking, including over-the-counter and herbal medications. Check with the patient’s primary care provider, cardiologist and psychiatrist about medication use, Dr. Muir said. “It’s a good time to revisit the need for all medications. Ask if the antidepressant can be changed, the blood pressure medicines. Can the patient hold their statin for 12 weeks?” he said.
Women taking oral contraceptives should be advised to try other methods of contraception, such as an intrauterine device or barrier methods. Additionally, pregnant women should not take either drug, as both are considered pregnancy category X, meaning the risks “clearly outweigh potential benefits,” according to the FDA.
Anemia and rashes are the two most common adverse events associated with the new therapies. Experts suggest physicians be proactive about managing both.
Before a patient starts therapy, do a pretreatment evaluation for anemia and consider the impact on comorbidities, such as cardiac and pulmonary disorders. Weigh the benefits of reducing the dose versus increasing or starting erythropoietin.
For rashes, patients should be proactive by moisturizing twice a day, limiting sun exposure and wearing loose-fitting clothing. Dr. Chung recommends including a dermatologist on the treatment team.
Keep an Eye on the ‘Holy Grail of Therapy’
One other important element that needs to be taken into account when considering patients for DAA therapy is whether patients should wait for something else to be approved, said Dr. Chung. Recent results from Phase II studies of second-generation DAAs suggest that some combination of these could be approved in the next three years (see “New Polymerase Inhibitor Could Become Cornerstone of Interferon-free HCV Treatment Regimen,” by Christina Frangou. Gastroenterology & Endoscopy News 2012;63[2]:16 and “Second Study of New Hep C Drug Is Promising for Difficult-to-Treat HCV Genotype 1 Patients,” by Christina Frangou. Gastroenterology & Endoscopy News 2012;63[2]:17-19). These therapies omit IFN from the treatment regimen and can generally be taken orally once a day, with or without food.
“That’s something critical to consider. With all the complexities of therapy—the issues of tolerability, adherence, drug–drug interactions, quality of life—there’s another equally important set of events going on, and that’s the emerging data on all-oral, interferon-free treatments,” said Dr. Chung. “It’s clear that the promise of interferon-sparing therapy is very real. For all of us, that would be the holy grail of therapy.”
Dr. Chung currently recommends that all patients with HCV infection who have advanced-stage disease, regardless of whether they are treatment-naive or experienced, should be considered for boceprevir or telaprevir, provided the benefits outweigh the risks. Patients who can reasonably defer treatment because of early-stage disease or who cannot tolerate IFN may be able to wait for investigational therapies to be approved. These patients also may be eligible for investigational studies, which are ongoing.
Dr. Muir disclosed that he is on advisory committees or review panels for Merck & Co., and Vertex Pharmaceuticals; is a consultant for Inhibitex, Merck & Co., and Vertex Pharmaceuticals; and receives grant/research support from Abbott Laboratories, Anadys, Bristol-Myers Squibb, Gilead, Medtronic, Merck & Co., Pfizer, Roche, Santaris, Scynexis and Vertex Pharmaceuticals. Dr. Chung receives grant/research support from Gilead, Merck & Co., Pfizer and Romark. Dr. Davis is a consultant for Vertex Pharmaceuticals and receives grant/research support from Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead, Novartis, Pharmasset, Tibotec and Vertex Pharmaceuticals.
Hepatology in Focus
ISSUE: FEBRUARY 2012 | VOLUME: 63
Patients’ Expectations About New HCV Direct-Acting Antivirals Often Unrealistic
Careful Patient Selection, Education Is Key for Success
by Christina Frangou
San Francisco—Soon after the FDA approved two direct-acting antiviral agents (DAAs) last spring for treating infection with hepatitis C virus (HCV), a 57-year-old black man came to see gastroenterologist Andrew Muir, MD.
The man had been diagnosed with hepatitis C in 2001. A liver biopsy one year later revealed he had stage II fibrosis. At the time, the patient declined treatment, saying the duration was too long and offered too few benefits.
But recently, he came back to Dr. Muir wanting to try a new protease inhibitor. Based on his reading, the man believed he could avoid interferon (IFN) and ribavirin (RBV), take a protease inhibitor as monotherapy for 24 weeks and expect a 75% chance of achieving a sustained virologic response (SVR).
Unfortunately, the patient’s expectations were unrealistic on all counts. The new protease inhibitor can only be given in conjunction with IFN and RBV, and the treatment duration varies. For blacks, therapy usually lasts a full 48 weeks, and in clinical trials, only 30% of black patients achieved an SVR with 28 weeks of therapy. Moreover, among black patients in the Phase III trials, SVR rates fell short of the 75% that the patient expected, and in treatment-naive blacks, only 62% receiving telaprevir and 53% on boceprevir achieved an SVR.
Educate To Encourage Adherence
Unrealistic expectations are common among patients with HCV infection who, after years of waiting for better therapies, are eager to try treatment with the new DAAs, said Dr. Muir. The DAAs on the market today are complex, with varied stoppage rules, monitoring points and some serious adverse events and drug–drug interactions.
“This is a real problem for clinicians. There’s tremendous excitement about these new therapies, but oftentimes, patients’ expectations are not in line with what these drugs can deliver,” said Dr. Muir, clinical director of hepatology at Duke University Medical Center, Durham, N.C.
In a presentation at The Liver Meeting 2011, Dr. Muir stressed that clinicians need to take time to carefully prepare patients for DAA therapy. Physicians must have clear, detailed discussions with their patients before and throughout treatment to optimize the benefits of DAA therapy, he said.
“The major challenges are preparing patients for the rigors of therapy, checking in frequently to make decisions about the duration of treatment and managing any issues as the patient goes along,” said Dr. Muir.
When patients come into the office considering treatment with DAAs, the first step is to clarify their expectations, said Dr. Muir. Patients need to learn the reality about DAAs if they want treatment to succeed.
Dr. Muir outlines for patients the complex prescribing rules, the contraindications, the lifestyle changes and duration of treatment with DAAs. The lifestyle changes can be significant, he cautions patients. Both telaprevir and boceprevir must be taken three times a day, or once every eight hours, and always with a meal. Dr. Muir then asks if the patient still wants treatment when these things are taken into account.
“That’s no small feat. Patients must adhere to that regimen because lapses in the concentration of telaprevir and boceprevir have historically been the risk period for breakthrough variants on therapy,” said Raymond Chung, MD, chief of hepatology and vice-chief of gastroenterology at Massachusetts General Hospital, Boston. Many of Dr. Chung’s patients limit or reschedule their work hours while on DAA therapy to help with adherence.
The key to getting patients through DAA treatment successfully is to select patients carefully and prepare them assiduously, said Gary L. Davis, MD, director of general and transplant hepatology at Baylor University Medical Center, Dallas. “This means that any issues that might impact compliance, tolerance and drug access should be dealt with before treatment starts. Educating the patient is essential. Patients and their support person need to clearly understand the importance of dosing compliance, lab monitoring and treatment stopping rules/end points.”
The treatment care team then needs to remain in close contact with the patient throughout treatment to reinforce adherence and offer feedback on their process, he added. At Dr. Chung’s office at Massachusetts General Hospital, one nurse practitioner has been assigned full-time to managing patients on DAAs. She works with them on everything from managing possible reactions like rash and anemia to helping them set up a daily schedule for taking the medications.
“We have 50 to 100 patients in varying stages of DAA treatment,” said Dr. Chung. “Every one of these patients is coming in for frequent visits—weekly in the beginning—and they are very much in need of monitoring, not just for adverse events like rash but also for fatigue and their ability to carry out work.”
Begin With a Thorough History
Before patients start the new therapies, gastroenterologists and hepatologists should consider getting a liver biopsy to help guide treatment, said Dr. Muir. Physicians also should confirm a patient’s history of treatment for HCV. If patients were previously on antiviral therapies, physicians need to find out as much as they can about that experience.
“You must ask whether we can improve upon previous treatment,” said Dr. Muir. “Were there adverse events with treatments? Were there dose reductions? If so, were they appropriate? How was patient adherence to medications? Did they use alcohol?”
Based on that information, physicians should outline the likelihood of each individual patient achieving an SVR, he said. The key predictors of SVR are whether patients are treatment-naive or treatment-experienced, whether they have cirrhosis and their race. Another important issue for patients is treatment duration. Duration will vary depending on each patient’s characteristics. “It’s important to speak with every patient about their likelihood of a shorter duration of treatment,” said Dr. Muir.
The American Association for the Study of Liver Diseases recommends 48 weeks of treatment for all patients with cirrhosis, as fewer patients with cirrhosis were included in the clinical trials that led to approval of the new drugs. Among those included, virologic response levels were lower than for patients without cirrhosis. For treatment-naive patients, 46% of non-black and 29% of black patients in the boceprevir SPRINT-2 (Serine Protease Inhibitor Therapy 2) trial achieved undetectable levels of HCV by 28 weeks, making them eligible for the shortened course of treatment (Poordad F et al. N Engl J Med 2011;364:1195-1206). In the telaprevir trial, 58% of patients had an early rapid virologic response (Jacobson IM et al. N Engl J Med 2011;364:2405-2416).
Patients’ interleukin-28B (IL28B) genotype also affects the expected duration of treatment. For both boceprevir and telaprevir, patients with the IL28B CC genotype are most likely to attain an early virologic response, more likely to receive a shortened course of therapy and more likely to have an SVR, according to studies presented at last year’s annual meeting of the European Association for the Study of the Liver.
Follow Through: Monitor for Response, Resistance, Reactions, Interactions
When the new HCV drugs were first approved, physicians’ offices reported some trouble getting approval from third-party payers for the full course of treatment, said Dr. Chung. His office had to provide documentation of successful early virologic response to get the go-ahead from payers to approve continuation of treatment with a protease inhibitor.
“You can imagine that if any gaps occur in the virologic tests or their reporting, this could lead to interruption of protease inhibitor therapy. It’s been a real challenge,” he said.
Experts recommend following patients very carefully over the course of treatment, monitoring any virologic breakthroughs or adverse reactions to the medications, particularly rash and anemia. Dr. Chung sees patients after the first, second and fourth week of therapy, and every four weeks thereafter if patients are having an uneventful course. Treatment monitoring is essential to prevent unwarranted continuation of treatment in patients when a breakthrough has occurred, he said.
“That would signal the emergence of resistant variants. Upon discovery, it would be paramount to discontinue the entire regimen to prevent selection of additional resistance mutations,” he said.
Equally important is the need to monitor patients closely for adverse reactions and drug–drug interactions. As IFN and RBV remain the backbone of this HCV regimen, the same contraindications exist as with standard dual therapy: decompensated cirrhosis, renal insufficiency, advanced cardiac/pulmonary disease, active depression, severe mental illness, anemia/neutropenia/thrombocytopenia and noncompliance.
Additionally, there are important drug–drug interactions with boceprevir and telaprevir. Both DAAs inhibit the CYP3A4/5 enzyme. Drugs metabolized by CYP3A4/5 may have increased effect in the presence of boceprevir or telaprevir. The DAAs themselves are metabolized by this cytochrome. As a result, other drugs that induce or inhibit CYP3A4/5 could affect HCV levels.
“Planning is key to deal with drug–drug interactions,” said Dr. Muir. It’s very important to do a risk–benefit analysis of treatment with boceprevir and telaprevir, taking into account patients’ comorbidities, he added.
It is important to review all drugs that the patient is taking, including over-the-counter and herbal medications. Check with the patient’s primary care provider, cardiologist and psychiatrist about medication use, Dr. Muir said. “It’s a good time to revisit the need for all medications. Ask if the antidepressant can be changed, the blood pressure medicines. Can the patient hold their statin for 12 weeks?” he said.
Women taking oral contraceptives should be advised to try other methods of contraception, such as an intrauterine device or barrier methods. Additionally, pregnant women should not take either drug, as both are considered pregnancy category X, meaning the risks “clearly outweigh potential benefits,” according to the FDA.
Anemia and rashes are the two most common adverse events associated with the new therapies. Experts suggest physicians be proactive about managing both.
Before a patient starts therapy, do a pretreatment evaluation for anemia and consider the impact on comorbidities, such as cardiac and pulmonary disorders. Weigh the benefits of reducing the dose versus increasing or starting erythropoietin.
For rashes, patients should be proactive by moisturizing twice a day, limiting sun exposure and wearing loose-fitting clothing. Dr. Chung recommends including a dermatologist on the treatment team.
Keep an Eye on the ‘Holy Grail of Therapy’
One other important element that needs to be taken into account when considering patients for DAA therapy is whether patients should wait for something else to be approved, said Dr. Chung. Recent results from Phase II studies of second-generation DAAs suggest that some combination of these could be approved in the next three years (see “New Polymerase Inhibitor Could Become Cornerstone of Interferon-free HCV Treatment Regimen,” by Christina Frangou. Gastroenterology & Endoscopy News 2012;63[2]:16 and “Second Study of New Hep C Drug Is Promising for Difficult-to-Treat HCV Genotype 1 Patients,” by Christina Frangou. Gastroenterology & Endoscopy News 2012;63[2]:17-19). These therapies omit IFN from the treatment regimen and can generally be taken orally once a day, with or without food.
“That’s something critical to consider. With all the complexities of therapy—the issues of tolerability, adherence, drug–drug interactions, quality of life—there’s another equally important set of events going on, and that’s the emerging data on all-oral, interferon-free treatments,” said Dr. Chung. “It’s clear that the promise of interferon-sparing therapy is very real. For all of us, that would be the holy grail of therapy.”
Dr. Chung currently recommends that all patients with HCV infection who have advanced-stage disease, regardless of whether they are treatment-naive or experienced, should be considered for boceprevir or telaprevir, provided the benefits outweigh the risks. Patients who can reasonably defer treatment because of early-stage disease or who cannot tolerate IFN may be able to wait for investigational therapies to be approved. These patients also may be eligible for investigational studies, which are ongoing.
Dr. Muir disclosed that he is on advisory committees or review panels for Merck & Co., and Vertex Pharmaceuticals; is a consultant for Inhibitex, Merck & Co., and Vertex Pharmaceuticals; and receives grant/research support from Abbott Laboratories, Anadys, Bristol-Myers Squibb, Gilead, Medtronic, Merck & Co., Pfizer, Roche, Santaris, Scynexis and Vertex Pharmaceuticals. Dr. Chung receives grant/research support from Gilead, Merck & Co., Pfizer and Romark. Dr. Davis is a consultant for Vertex Pharmaceuticals and receives grant/research support from Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead, Novartis, Pharmasset, Tibotec and Vertex Pharmaceuticals.
CDC recognizes HCV deaths are up, ponders changing HCV screening guidelines...
Posted on 2/20/12 in the Wall Street Journal. The CDC muses updating their testing guidelines to recommend that anyone born between 1945 and 1965 get a one-time HCV screening based on recent data. This includes a Stanford University study that despite the hefty price tag that comes with HCV therapy, it would be cost-effective for people with advanced disease vs the cost associated with transplant or potentially dying from liver cancer. The study also concluded that gene testing, like the IL28B polymorphism assay, may be useful for those in the very early stages of disease to predict who could benefit from the less-expensive two drug regimen of PEG-inteferon + RBV vs the costly triple drug regimen of PEG-interferon + RBV + Protease Inhibitor. Sounds like a pragmatic approach to me.
FEBRUARY 20, 2012, 5:01 P.M. ET.Hepatitis C deaths up, baby boomers most at risk .
Associated Press
WASHINGTON — Deaths from liver-destroying hepatitis C are on the rise, and new data shows baby boomers especially should take heed — they are most at risk.
Federal health officials are considering whether anyone born between 1945 and 1965 should get a one-time blood test to check if their livers harbor this ticking time bomb. The reason: Two-thirds of people with hepatitis C are in this age group, most unaware that a virus that takes a few decades to do its damage has festered since their younger days.
The issue has taken new urgency since two drugs hit the market last summer that promise to cure many more people than ever was possible. And research published Monday says testing millions of the middle-aged to find those who need the pricey treatment would be worth the cost, saving thousands of lives.
"One of every 33 baby boomers are living with hepatitis C infection," says Dr. John Ward, hepatitis chief at the Centers for Disease Control and Prevention. "Most people will be surprised, because it's a silent epidemic."
Don't think you need to worry? Yes, sharing a needle while injecting illegal drugs is the biggest risk factor for becoming infected with this blood-borne virus. But before 1992, when widespread testing of the blood supply began, hepatitis C commonly was spread through blood transfusions. Plus, a one-time experiment with drugs way back in high school or college could have been enough.
"Asking someone about a risk that happened 20 to 30 years ago is a lot to ask," says Ward. Hence the quest for a new strategy.
About 3.2 million Americans are estimated to have chronic hepatitis C, but at least half of them may not know it. The virus, which affects 170 million people worldwide, can gradually scar the liver and lead to cirrhosis or liver cancer. It is a leading cause of liver transplants.
A CDC study published Monday analyzed a decade of death records and found an increase in death rates from hepatitis C. In fact, in 2007 there were 15,000 deaths related to hepatitis C, higher than previous estimates — and surpassing the nearly 13,000 deaths caused by the better-known AIDS virus.
Perhaps more surprising, three-fourths of the hepatitis deaths occurred in the middle-aged, people 45 to 64, researchers reported in Annals of Internal Medicine.
"Mortality will continue to grow for the next 10 to 15 years at least unless we do something different" to find and treat the silent sufferers, Ward says.
CDC's current guidelines recommend testing people known to be at high risk, and until last summer there wasn't much enthusiasm even for that step: the reasons are the year-long, two-drug treatment promised to cure only 40 percent of people; treatment was so grueling that many patients refused to try it and treatment could cost up to $30,000.
Two new drugs — Vertex Pharmaceuticals' telaprevir and Merck & Co.'s boceprevir — are starting to change that pessimism. Research suggests adding one of them to standard therapy can boost cure rates as high as 75 percent. While still full of side effects, they can allow some people to finish treatment in just six months. They add to the price, however, another $1,000 to $4,000 a week. Drugs that promise to work even better have begun testing.
Those advances are fueling CDC deliberations of whether to change testing guidelines to recommend that anyone born between 1945 and 1965 get a one-time screening. A second CDC-funded study published Monday analyzed models of that option, and concluded it had the potential to save 82,000 lives.
A third study published Monday from Stanford University looked more closely at the price tag, and concluded the new triple-therapy would be cost-effective for people with advanced disease. It's still cheaper than a transplant costing well over $100,000. But not everyone with hepatitis C will go on to suffer serious liver damage. For those with mild disease, that analysis concluded some gene testing to predict who might really need the costlier triple therapy rather than the older drugs would be a good next step.
It's not clear how quickly the CDC will settle the boomer-screening question. But doctors at New York's Montefiore Medical Center have started raising the issue with boomers. And Montefiore internist Dr. Gary Rogg says a number of patients have sought testing after seeing hepatitis-awareness ads from the drugs' manufacturers.
"Now it's considered a curable disease, that makes all the difference," says Rogg, who was surprised at some longtime patients' test results. Even a nurse he knows learned she had it, and the only risk she could recall was a blood transfusion during surgery when she was 10 years old.
___
EDITOR's NOTE — Lauran Neergaard covers health and medical issues for The Associated Press in Washington.
___
Online: Centers for Disease Control and Prevention: http://www.cdc.gov/
Montefiore Medical Center: http://bit.ly/u6scH0
Monday, February 20, 2012
Taiwan offers new model to predict hepatitis C cancer risk...
Posted on Focus Taiwan News Channel on 2/19/12. At the Conference for Asian Pacific Association for the Study of the Liver, Taiwanese researchers presented a successful new predictive model to calculate the likelihood of patients developing liver cancer. They claim a 80% accuracy rate and hope that the model bolsters their hypothesis that treating HCV and HBV early can help prevent liver cancer.
Taiwan offers new model to predict hepatitis C cancer risk
2012/02/19 20:14:20
Taipei, Feb. 19 (CNA) A Taiwan-led research team has successfully devised a new prediction model to calculate the likelihood of hepatitis C patients developing liver cancer, the team leader said Sunday.
The model incorporates indicators such as age, the liver function indexes ALT and AST, hepatitis C virus RNA in serum, cirrhosis and the genotype of the virus, said Chen Chien-jen at a session of the Conference of the Asian Pacific Association for the Study of the Liver held in Taipei.
Chen, vice president of Taipei-based Academia Sinica, said the serum data was particularly important in predicting the chances of developing liver cancer.
The model, which can predict a result with 80 percent accuracy, assigns a score on 0-25 scale to analyze each case. The higher the score, the higher the risk of getting liver cancer, Chen said.
Hepatitis B and C viruses are the main causes of liver cancer in Taiwan, Chen said, with 20-25 percent of liver cancer cases triggered by the hepatitis C virus and 70-75 percent by the hepatitis B virus.
Close to 3 million people in Taiwan's 23-million population carry the hepatitis B virus, while some 600,000 carry the hepatitis C virus, according to the Department of Health.
With the model, "we hope to identify those facing higher risk of getting liver cancer and treat them as early as possible," Chen said.
Chen's team also launched a model in 2010 to calculate the chances of the hepatitis B virus developing into liver cancer.
In the future, the prediction models will be available on the Internet and in apps on smartphones to allow individuals to determine their own risk factor, Chen said.
Friday, February 17, 2012
Gilead Sciences announces viral relapse in 12 week GS-7977 + RBV ELECTRON arm...
Gilead press release on 2/17/12. The press release that shook the HCV drug development world. Gilead announced that they had data for 8 out of 10 previous null-responder subjects randomized to the 12 week GS-7977 + RBV arm in the ELECTRON trial. Out of the 8 patients, 6 developed viral relapse. Data on the other two patients is forthcoming. So, this counts out GS-7977 + RBV for 12 weeks as effective therapy for previous null responders. The questions that remain are: can therapy extended past 12 weeks do the job? (say 24, 36 or even 48)? Does this regimen require the addition of one or more additional DAAs that target differing parts of the HCV replication process? Or the addition of interferon? Or both of the latter? This is clearly not a reason to panic (although, judging from the stock drop today, shareholders did do just that) but it did answer 'no' to an important question this study was designed to answer - is 12 weeks of GS-7977 + RBV enough to achieve an SVR in the null responder patient population? Gilead will look at multiple combinations of treatment durations and drug combinations to find the one that achieves the best results. Gilead also has an excellent portfolio of HCV drugs that inhibit differing parts of the HCV replication process to pair with GS-7977. So panic is definitely not warranted.
It is a warning to analysts who touted an inteferon-free GS-7977 + RBV as the answer to all patient types. Such statements were misleading to their investors. We can learn from the early research days of HIV. I don't want to say "I told you so", but "I told you so". The HCV virus is a highly replicating virus with no proof-reading mechanism capable of making every possible mutation of itself in the course of a day. As in HIV, one drug will not be able to stop the virus from replicating and will select out the mutations that are resistant to the drug and are most fit to survive in the presence of drug. It will take more than one drug targeting more than one part of the viral replication process to do the trick, and may also require the generalized immune response triggered by exogenous interferon as much as we'd like to see that go away.
Gilead Announces Data for Genotype 1 Null Responder Hepatitis C Patients Enrolled in ELECTRON Study
– Viral Relapse Seen Post Treatment with GS-7977 Plus Ribavirin –
– Awaiting Data for Treatment-Naïve Genotype 1 Patients –
Press Release: Gilead Sciences, Inc.
.
FOSTER CITY, Calif.--(BUSINESS WIRE)--
Gilead Sciences, Inc. (NASDAQ:GILD - News) announced today that the majority of hepatitis C genotype 1 patients with a prior “null” response to an interferon (IFN)-containing regimen enrolled in the ongoing ELECTRON study experienced viral relapse within four weeks of completing 12 weeks of treatment with GS-7977 plus ribavirin (RBV). Ten patients were randomized to this arm of the ELECTRON study and data are available for eight of the 10 patients at this time. Among these eight patients, six have experienced viral relapse. Two patients have not relapsed; however, they have only reached the two week post-treatment time point.
“These data answer an important question about the use of GS-7977 and ribavirin for the treatment of genotype 1 null responder patients, suggesting that additional direct acting antivirals may be necessary to effectively treat this patient population,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer. “We will continue to explore a number of therapeutic approaches to address this significant unmet medical need, including combinations with other oral antivirals.”
GS-7977 is a nucleotide analog polymerase inhibitor that is currently being studied for the treatment of chronic hepatitis C. A number of ongoing Phase 2 and Phase 3 studies are evaluating the safety and efficacy of the compound with and without RBV and/or pegylated interferon (Peg-IFN) in patients with genotypes 1-6 who are treatment naïve, treatment experienced, or have had a “null” response to Peg-IFN.
Genotype 2 and 3 data from the ELECTRON study were presented at the 62nd annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2011). Data from the genotype 1 null responder arm of the study will be presented at an upcoming scientific conference.
Results from ongoing studies in genotype 1 treatment-naïve patients will be available in the coming months. The first data evaluating GS-7977 plus RBV for 12 weeks in genotype 1 naïve patients will come from an arm of the QUANTUM study with 25 patients at the end of the first quarter of 2012. This will be followed in the second quarter by data from the ELECTRON study involving 25 patients and, early in the third quarter, data on GS-7977 and RBV treatment for 24 weeks from an arm of the QUANTUM study will become available.
Conference Call
Gilead will host a conference call today, February 17, 2012 at 8:00 a.m. Eastern Time, to discuss these study results. To access the live call, please dial 1-866-825-1709 (U.S.) or 1-617-213-8060 (international). The conference passcode number is 71588571. Telephone replay is available approximately one hour after the call through 11:59 p.m. Eastern Time, February 20, 2012. To access, please call 1-888-286-8010 (U.S.) or 1-617-801-6888 (international). The conference passcode number for the replay is 64278864. The information provided on the teleconference is only accurate at the time of the conference call, and Gilead will take no responsibility for providing updated information.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from the ELECTRON and QUANTUM studies, including in genotype 1 treatment-naïve patients, as well as other clinical trials evaluating GS-7977 with or without RBV and/or Peg-IFN or in combination with other antivirals; the anticipated timing for receiving clinical data and making regulatory filings; and Gilead’s ability to develop an all-oral antiviral regimen for HCV genotype 1 patients or a pangenotypic regimen for all HCV patients. As a result, GS-7977 may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of GS-7977 if, for example, it believes commercialization will be difficult relative to other opportunities in its pipeline. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2011, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company’s website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
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Contact:.
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Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Amy Flood, 650-522-5643 (Media)
Wednesday, February 15, 2012
Hepatitis C: Drugmakers jockey to create cocktail...
Bloomberg News article published in the San Francisco Chronicle on 2/15/2012 on the recent M&As and speculation on the M&As to come. Very nice overview if you're new to the HCV drug development space and have a hankerin' to learn who the big players are.
Hepatitis C: Drugmakers jockey to create cocktail
Bloomberg News
Wednesday, February 15, 2012
A developing medical theory that hepatitis C can be overcome with the same type of drug cocktails that tamed HIV is shaking up the pharmaceutical industry.
Companies are trying to anticipate which medicines might work best together and planning their acquisition strategies accordingly. Because only a few hepatitis C drugs are approved, and others in testing may not pan out, "we don't know what the winning formula will be," said Ben Weintraub, an analyst at Wolters Kluwer InThought. To raise the odds, "companies are doing M&A (mergers and aquisitions) and starting new trials on almost a daily basis."
With more than two dozen drugs in development, doctors predict a new age of therapy for a blood-borne virus carried by 170 million people that now has few treatment options. The promise of a potential $20 billion market has already spurred three deals in the past year - the latest being Bristol-Myers Squibb's $2.5 billion purchase this month of Inhibitex.
Next in line may be Idenix Pharmaceuticals and Achillion Pharmaceuticals, said Raghuram Selvaraju, an analyst with Morgan Joseph TriArtisan.
"I don't think either of these companies will remain independent very long," Selvaraju said. "I think we'll see both of them out of there by the end of the year."
Increased urgency
Achillion is testing a so-called protease inhibitor, while Idenix is developing a nucleotide polymerase inhibitor. The two medicines, which work differently to block the virus' ability to replicate in the body, are in the second of three stages of testing normally required for U.S. approval.
By combining several classes of these new hepatitis C drugs, doctors may be able to limit the virus' ability to infect, mimicking the strategy that a decade earlier helped turn HIV from a killer disease to a controlled one, said Charles Chiu, an infectious disease doctor at UCSF.
With the success of treatments that "work on the virus itself, there's an increased urgency now to explore drugs in many different stages of the viral life cycle," Chui said.
Until last year's introduction of Victrelis from Merck and Incivek by Vertex Pharmaceuticals - two protease inhibitors - the standard treatment combined the antiviral drug ribavirin with interferon, an immune-boosting protein sold by Merck as PegIntron and by Roche as Pegasys.
That treatment relied on interferon shots given weekly for a year, and it cured only about half of patients with the most common U.S. strain, called genotype 1. The drugs also caused side effects that include fatigue and flu-like symptoms.
Across different types
The new protease inhibitors stop an enzyme that splits proteins and allows them to replicate. While they've been shown to cure more patients in less time than previous therapies, with fewer side effects, they still need to be combined with interferon shots.
Scientists see promise in the other class being developed, the nucleotide polymerase inhibitors, which bind to a different part of the virus than the protease inhibitors. These drugs are pan-genotypic - meaning they are effective across the different types of hepatitis C. They could become the backbone for an interferon-free combination.
Mixing the classes together may be even more effective in beating the disease, which is blamed for more than 350,000 deaths a year worldwide.
"We waited 15 years for protease inhibitors, and a year later we could have a new class of drugs, nucleotides, that surpass them," said Steve Worland, former CEO of Anadys Pharmaceuticals, an experimental hepatitis C drugmaker acquired by Roche in November for about $230 million. "That kind of dramatic change I have never seen before."
Drugmakers want to own a piece of the eventual cocktail that will work best among patients worldwide. They've been working in the lab to create their own drugs, as well as scouting other companies with an eye toward buying promising candidates.
Takeover targets
Foster City's Gilead Sciences paid $10.8 billion for Pharmasset last month to use its experimental nucleotide drug, PSI-7977, as a cornerstone to a new hepatitis C combination - one that it expects other drugmakers will want to use - opening the door to added licensing revenue.
Selvaraju said: "7977 is going to be the driver of an all-oral regimen, and all of these other drugs are going to be layered on top of it."
Rivals have the same idea as they hunt for potential targets. That's why Achillion and Idenix are being closely watched as potential takeover targets, Selvaraju said. Abbott Laboratories and Roche are potential bidders, he said. Merck, Bristol-Myers and Johnson & Johnson are also in pursuit of the new regimens.
The potential market size for these therapies is at least $20 billion, according to Michael Kishbauch, CEO of Achillion.
Competition grows
Gilead increased its offer to acquire Pharmasset four times last year to $137 per share from $100 per share, after a clinical trial showed PSI-7977 cured all patients in a study.
"The opportunity to be able to cure people with three months of therapy is one of the most amazing breakthroughs we can bring to health care - and there's a lot of competition," Gilead CEO John Martin said last month.
Idenix is in talks to find a partner to create a combination hepatitis C treatment, said Ron Renaud, the company's CEO. While declining to comment on whether the company may be acquired, he said interest in hepatitis C drugs picked up last year during a liver disease conference.
"There is a tremendous market opportunity here that people want to take advantage of, and there's an intense race that's under way to get to that point," Renaud said.
http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2012/02/15/BUDC1N7L0U.DTL
his article appeared on page D - 1 of the San Francisco Chronicle
Hepatitis C: Drugmakers jockey to create cocktail
Bloomberg News
Wednesday, February 15, 2012
A developing medical theory that hepatitis C can be overcome with the same type of drug cocktails that tamed HIV is shaking up the pharmaceutical industry.
Companies are trying to anticipate which medicines might work best together and planning their acquisition strategies accordingly. Because only a few hepatitis C drugs are approved, and others in testing may not pan out, "we don't know what the winning formula will be," said Ben Weintraub, an analyst at Wolters Kluwer InThought. To raise the odds, "companies are doing M&A (mergers and aquisitions) and starting new trials on almost a daily basis."
With more than two dozen drugs in development, doctors predict a new age of therapy for a blood-borne virus carried by 170 million people that now has few treatment options. The promise of a potential $20 billion market has already spurred three deals in the past year - the latest being Bristol-Myers Squibb's $2.5 billion purchase this month of Inhibitex.
Next in line may be Idenix Pharmaceuticals and Achillion Pharmaceuticals, said Raghuram Selvaraju, an analyst with Morgan Joseph TriArtisan.
"I don't think either of these companies will remain independent very long," Selvaraju said. "I think we'll see both of them out of there by the end of the year."
Increased urgency
Achillion is testing a so-called protease inhibitor, while Idenix is developing a nucleotide polymerase inhibitor. The two medicines, which work differently to block the virus' ability to replicate in the body, are in the second of three stages of testing normally required for U.S. approval.
By combining several classes of these new hepatitis C drugs, doctors may be able to limit the virus' ability to infect, mimicking the strategy that a decade earlier helped turn HIV from a killer disease to a controlled one, said Charles Chiu, an infectious disease doctor at UCSF.
With the success of treatments that "work on the virus itself, there's an increased urgency now to explore drugs in many different stages of the viral life cycle," Chui said.
Until last year's introduction of Victrelis from Merck and Incivek by Vertex Pharmaceuticals - two protease inhibitors - the standard treatment combined the antiviral drug ribavirin with interferon, an immune-boosting protein sold by Merck as PegIntron and by Roche as Pegasys.
That treatment relied on interferon shots given weekly for a year, and it cured only about half of patients with the most common U.S. strain, called genotype 1. The drugs also caused side effects that include fatigue and flu-like symptoms.
Across different types
The new protease inhibitors stop an enzyme that splits proteins and allows them to replicate. While they've been shown to cure more patients in less time than previous therapies, with fewer side effects, they still need to be combined with interferon shots.
Scientists see promise in the other class being developed, the nucleotide polymerase inhibitors, which bind to a different part of the virus than the protease inhibitors. These drugs are pan-genotypic - meaning they are effective across the different types of hepatitis C. They could become the backbone for an interferon-free combination.
Mixing the classes together may be even more effective in beating the disease, which is blamed for more than 350,000 deaths a year worldwide.
"We waited 15 years for protease inhibitors, and a year later we could have a new class of drugs, nucleotides, that surpass them," said Steve Worland, former CEO of Anadys Pharmaceuticals, an experimental hepatitis C drugmaker acquired by Roche in November for about $230 million. "That kind of dramatic change I have never seen before."
Drugmakers want to own a piece of the eventual cocktail that will work best among patients worldwide. They've been working in the lab to create their own drugs, as well as scouting other companies with an eye toward buying promising candidates.
Takeover targets
Foster City's Gilead Sciences paid $10.8 billion for Pharmasset last month to use its experimental nucleotide drug, PSI-7977, as a cornerstone to a new hepatitis C combination - one that it expects other drugmakers will want to use - opening the door to added licensing revenue.
Selvaraju said: "7977 is going to be the driver of an all-oral regimen, and all of these other drugs are going to be layered on top of it."
Rivals have the same idea as they hunt for potential targets. That's why Achillion and Idenix are being closely watched as potential takeover targets, Selvaraju said. Abbott Laboratories and Roche are potential bidders, he said. Merck, Bristol-Myers and Johnson & Johnson are also in pursuit of the new regimens.
The potential market size for these therapies is at least $20 billion, according to Michael Kishbauch, CEO of Achillion.
Competition grows
Gilead increased its offer to acquire Pharmasset four times last year to $137 per share from $100 per share, after a clinical trial showed PSI-7977 cured all patients in a study.
"The opportunity to be able to cure people with three months of therapy is one of the most amazing breakthroughs we can bring to health care - and there's a lot of competition," Gilead CEO John Martin said last month.
Idenix is in talks to find a partner to create a combination hepatitis C treatment, said Ron Renaud, the company's CEO. While declining to comment on whether the company may be acquired, he said interest in hepatitis C drugs picked up last year during a liver disease conference.
"There is a tremendous market opportunity here that people want to take advantage of, and there's an intense race that's under way to get to that point," Renaud said.
http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2012/02/15/BUDC1N7L0U.DTL
his article appeared on page D - 1 of the San Francisco Chronicle
BioCryst releases preclinical results for HCV nucleoside inhibitor BCX5191
Posted 2/15/12 on Business Wire - BioCryst announce pre-clinical results for their once-a-day (concieveably) pan-genotypic polymerase inhibitor BCX5191, with first in-human study planned for Q4 2012. The authors of the press release invoke "GS-7977" in comparsion to BCX5191 in terms of internal comparative preclinical studies.
BioCryst Announces Promising Results from Preclinical Studies of BCX5191 for Hepatitis C
•BCX5191: Planning to file for first–in-human studies during the fourth quarter 2012
•BioCryst to discuss study outcomes during its 2011 results call February 16 at 11:00 a.m. ET
RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--BioCryst Pharmaceuticals, Inc. (NASDAQ: BCRX) today announced favorable preclinical results for BCX5191, a novel adenine nucleoside analog targeting viral RNA polymerase for the potential treatment of hepatitis C.
“Based on our internal comparative preclinical studies of BCX5191 with the most advanced nucleotide analog in clinical development, GS-7977, we believe BCX5191 has the potential to be the backbone of best-in-class oral treatment regimens for hepatitis C patients.”
.BioCryst has successfully completed in vitro and in vivo studies in which BCX5191 exhibited potent and selective pan-genotypic antiviral activity against the hepatitis C polymerase enzyme. BCX5191 showed no inhibition of human RNA polymerase and no evidence of toxicity from standard in vitro screens.
Human liver cells rapidly and efficiently convert BCX5191 into its active triphosphate form. BCX5191 does not require prodrug technology to achieve bioavailability. BCX5191 inhibits the viral RNA polymerase enzyme across genotypes 1-4 at sub-micromolar concentrations (0.05-0.36 µM) and is active in replicon cell assays for genotypes 1a and 1b.
In preclinical models, BCX5191 demonstrates high oral bioavailability, and the drug is actively transported into the liver. Following a single oral dose in rats, liver BCX5191 triphosphate levels exceed the IC50 values for genotypes 1-4 through 24 hours. At Cmax, the drug triphosphate level is more than 100 times the IC50. This pharmacokinetic profile is expected to support once-daily dosing in clinical studies.
“BCX5191 has met stringent preclinical criteria to advance to IND-enabling studies. We expect this program to be ready to file for first-in-human studies during the fourth quarter of 2012,” said Dr. William P. Sheridan, Senior Vice President & Chief Medical Officer of BioCryst Pharmaceuticals. “Based on our internal comparative preclinical studies of BCX5191 with the most advanced nucleotide analog in clinical development, GS-7977, we believe BCX5191 has the potential to be the backbone of best-in-class oral treatment regimens for hepatitis C patients.”
Additional BCX5191 non-clinical experiments are ongoing or planned, including Good Laboratory Practices (GLP) non-clinical safety studies and in vitro evaluation of BCX5191 in combination with ribavirin.
Conference Call and Webcast
BioCryst's leadership team will host a conference call and webcast on Thursday, February 16, 2012 at 11:00 a.m. Eastern Time to discuss financial results and recent corporate developments, including results from the BCX5191 hepatitis C program. To participate in the conference call, please dial 1-877-303-8027 (United States) or 1-760-536-5165 (International). No passcode is needed for the call. The webcast and accompanying slides can be accessed by logging onto www.BioCryst.com. Accompanying slides will be available on the BioCryst website several hours prior to the call. Please connect to the website at least 15 minutes prior to the start of the conference call to ensure adequate time for any software download that may be necessary.
About Hepatitis C
Hepatitis C is a contagious liver disease that results from infection with the hepatitis C virus (HCV), which is the most common virus that infects the liver and can lead to life-threatening liver problems, such as liver damage, cirrhosis, liver failure or liver cancer. There are an estimated 170 million individuals worldwide who are chronically infected with HCV, and about 3 to 4 million people are infected annually. In the United States, there are approximately 4 million people who have chronic hepatitis C.
About BioCryst
BioCryst Pharmaceuticals designs, optimizes and develops novel small-molecule pharmaceuticals that block key enzymes involved in infectious diseases, inflammatory diseases and cancer. BioCryst currently has three novel late-stage compounds in development: peramivir, a neuraminidase inhibitor for the treatment of influenza, BCX4208, a purine nucleoside phosphorylase (PNP) inhibitor for the treatment of gout, and forodesine, an orally-available PNP inhibitor for cancer, which is being developed by Mundipharma under a global license agreement. Utilizing crystallography and structure-guided drug design, BioCryst continues to discover additional compounds and to progress others through preclinical and early development to address the unmet medical needs of patients and physicians. For more information, please visit the Company's website at http://www.biocryst.com/.
Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: that there can be no assurance that our compounds will prove effective in clinical studies; that development and commercialization of our compounds may not be successful; that we or our licensees may not be able to enroll the required number of subjects in planned clinical trials of our product candidates and that such clinical trials may not be successfully completed; that BioCryst or its licensees may not commence as expected human clinical trials with BCX5191; that ongoing and future preclinical and clinical development may not have positive results; that we or our licensees may not be able to continue future development of our current and future development programs; that our development programs may never result in future product, license or royalty payments being received by BioCryst; that BioCryst may not reach favorable agreements with potential pharmaceutical and biotechnology partners for further development of BCX5191; that our actual cash burn rate may not be consistent with our expectations; that BioCryst may not have sufficient cash to continue funding the development, manufacturing, marketing or distribution of its products and that additional funding, if necessary, may not be available at all or on terms acceptable to BioCryst. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst's most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and current reports on Form 8-K, all of which identify important factors that could cause the actual results to differ materially from those contained in our projections and forward-looking statements.
BCRXW
Contacts
BioCryst Pharmaceuticals
Robert Bennett, 919-859-7910 (investors)
or
WCG
Catherine Kyroulis, 212-301-7174 (media)
BioCryst Announces Promising Results from Preclinical Studies of BCX5191 for Hepatitis C
•BCX5191: Planning to file for first–in-human studies during the fourth quarter 2012
•BioCryst to discuss study outcomes during its 2011 results call February 16 at 11:00 a.m. ET
RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--BioCryst Pharmaceuticals, Inc. (NASDAQ: BCRX) today announced favorable preclinical results for BCX5191, a novel adenine nucleoside analog targeting viral RNA polymerase for the potential treatment of hepatitis C.
“Based on our internal comparative preclinical studies of BCX5191 with the most advanced nucleotide analog in clinical development, GS-7977, we believe BCX5191 has the potential to be the backbone of best-in-class oral treatment regimens for hepatitis C patients.”
.BioCryst has successfully completed in vitro and in vivo studies in which BCX5191 exhibited potent and selective pan-genotypic antiviral activity against the hepatitis C polymerase enzyme. BCX5191 showed no inhibition of human RNA polymerase and no evidence of toxicity from standard in vitro screens.
Human liver cells rapidly and efficiently convert BCX5191 into its active triphosphate form. BCX5191 does not require prodrug technology to achieve bioavailability. BCX5191 inhibits the viral RNA polymerase enzyme across genotypes 1-4 at sub-micromolar concentrations (0.05-0.36 µM) and is active in replicon cell assays for genotypes 1a and 1b.
In preclinical models, BCX5191 demonstrates high oral bioavailability, and the drug is actively transported into the liver. Following a single oral dose in rats, liver BCX5191 triphosphate levels exceed the IC50 values for genotypes 1-4 through 24 hours. At Cmax, the drug triphosphate level is more than 100 times the IC50. This pharmacokinetic profile is expected to support once-daily dosing in clinical studies.
“BCX5191 has met stringent preclinical criteria to advance to IND-enabling studies. We expect this program to be ready to file for first-in-human studies during the fourth quarter of 2012,” said Dr. William P. Sheridan, Senior Vice President & Chief Medical Officer of BioCryst Pharmaceuticals. “Based on our internal comparative preclinical studies of BCX5191 with the most advanced nucleotide analog in clinical development, GS-7977, we believe BCX5191 has the potential to be the backbone of best-in-class oral treatment regimens for hepatitis C patients.”
Additional BCX5191 non-clinical experiments are ongoing or planned, including Good Laboratory Practices (GLP) non-clinical safety studies and in vitro evaluation of BCX5191 in combination with ribavirin.
Conference Call and Webcast
BioCryst's leadership team will host a conference call and webcast on Thursday, February 16, 2012 at 11:00 a.m. Eastern Time to discuss financial results and recent corporate developments, including results from the BCX5191 hepatitis C program. To participate in the conference call, please dial 1-877-303-8027 (United States) or 1-760-536-5165 (International). No passcode is needed for the call. The webcast and accompanying slides can be accessed by logging onto www.BioCryst.com. Accompanying slides will be available on the BioCryst website several hours prior to the call. Please connect to the website at least 15 minutes prior to the start of the conference call to ensure adequate time for any software download that may be necessary.
About Hepatitis C
Hepatitis C is a contagious liver disease that results from infection with the hepatitis C virus (HCV), which is the most common virus that infects the liver and can lead to life-threatening liver problems, such as liver damage, cirrhosis, liver failure or liver cancer. There are an estimated 170 million individuals worldwide who are chronically infected with HCV, and about 3 to 4 million people are infected annually. In the United States, there are approximately 4 million people who have chronic hepatitis C.
About BioCryst
BioCryst Pharmaceuticals designs, optimizes and develops novel small-molecule pharmaceuticals that block key enzymes involved in infectious diseases, inflammatory diseases and cancer. BioCryst currently has three novel late-stage compounds in development: peramivir, a neuraminidase inhibitor for the treatment of influenza, BCX4208, a purine nucleoside phosphorylase (PNP) inhibitor for the treatment of gout, and forodesine, an orally-available PNP inhibitor for cancer, which is being developed by Mundipharma under a global license agreement. Utilizing crystallography and structure-guided drug design, BioCryst continues to discover additional compounds and to progress others through preclinical and early development to address the unmet medical needs of patients and physicians. For more information, please visit the Company's website at http://www.biocryst.com/.
Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: that there can be no assurance that our compounds will prove effective in clinical studies; that development and commercialization of our compounds may not be successful; that we or our licensees may not be able to enroll the required number of subjects in planned clinical trials of our product candidates and that such clinical trials may not be successfully completed; that BioCryst or its licensees may not commence as expected human clinical trials with BCX5191; that ongoing and future preclinical and clinical development may not have positive results; that we or our licensees may not be able to continue future development of our current and future development programs; that our development programs may never result in future product, license or royalty payments being received by BioCryst; that BioCryst may not reach favorable agreements with potential pharmaceutical and biotechnology partners for further development of BCX5191; that our actual cash burn rate may not be consistent with our expectations; that BioCryst may not have sufficient cash to continue funding the development, manufacturing, marketing or distribution of its products and that additional funding, if necessary, may not be available at all or on terms acceptable to BioCryst. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst's most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and current reports on Form 8-K, all of which identify important factors that could cause the actual results to differ materially from those contained in our projections and forward-looking statements.
BCRXW
Contacts
BioCryst Pharmaceuticals
Robert Bennett, 919-859-7910 (investors)
or
WCG
Catherine Kyroulis, 212-301-7174 (media)
Monday, February 13, 2012
TMC435 activity in HCV genotypes 2-6...
For your comments - Posted on 2/12/12 in the 'Articles in Press' section of the Journal of Hepatology. From the results of the Phase IIa study,Janssen's TMC435 HCV protease inhibitor appears to have activity in HCV genotypes 2,4,5 & 6, with potency being most apparent in 6,4,2 in that order. TMC435 seems to share the lack of activity in genotype 3 HCV with it's predecessors Telaprevir and Boceprevir.
Article in Press Antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2 to 6: TMC435-C202, a phase IIa, open-label study Journal of Hepatology Feb 12 2012 Background & Aims TMC435 is an investigational, once-daily, oral NS3/4A protease inhibitor currently in phase III development for the treatment of hepatitis C virus (HCV) infection. Phase I and II studies in patients infected with HCV genotype 1 have demonstrated that TMC435 is generally well tolerated, has a pharmacokinetic profile that supports once daily dosing, and demonstrates potent antiviral activity. This phase IIa study (TMC435-C202; NCT00812331) was conducted to investigate the antiviral activity, safety, tolerability, and pharmacokinetics of TMC435 in treatment-naїve patients infected with HCV genotypes 2 to 6. Methods The study consisted of 7 days of monotherapy with TMC435 (200 mg once daily). Patients could begin treatment with pegylated interferon/ribavirin from Day 8 with a follow-up period up to Days 37–42. Results Thirty-seven patients were enrolled in Germany, Belgium and Thailand. For the primary endpoint at Day 8, the mean (±standard error) change in plasma HCV ribonucleic acid (log10 IU/mL) from baseline was greatest for genotypes 6 (-4.35±0.29) and 4 (-3.52±0.43), followed by genotypes 2 (-2.73±0.71) and 5 (-2.19±0.39). No antiviral activity was evident for genotype 3. Viral breakthrough occurred in six patients during the monotherapy phase and in six additional patients during PegIFN/RBV-only period. All adverse events were mild or moderate and there were no discontinuations during the TMC435 monotherapy period. Conclusions The results of this phase IIa proof-of-concept trial provide evidence that TMC435 has a spectrum of activity against multiple HCV genotypes, except for genotype 3. In this study, TMC435 was generally safe and well tolerated.
BMS completes tender offer for Inhibitex Inc...
Bristol-Myers completes Inhibitex tender offer
TRENTON, N.J. (AP) — Bristol-Myers Squibb Co. said Monday that it's completed its tender offer for the stock of Inhibitex Inc., a drug developer that Bristol is buying for $2.5 billion as part of its strategy to become a player in the hot hepatitis C drug market.
New York-based Bristol-Myers said it now has about 91 percent of outstanding shares of Inhibitex, after buying just over 77.5 million shares through midnight Friday for $26 each.
That's the last step before the merger can be executed. A Bristol-Myers spokeswoman on Monday said the company is working to quickly complete the deal but could not say when it will close.
When that happens, remaining Inhibitex shares will be canceled, their owners will be able to receive $26 per share and Inhibitex will become a wholly owned subsidiary of Bristol-Myers.
Earlier in February, the federal antitrust review period under the Hart-Scott-Rodino Antitrust act expired, satisfying a key condition of the offer.
Bristol-Myers is an important maker of medicines for viruses, including Baraclude for hepatitis B and several HIV drugs, but has nothing for hepatitis C at a time when more patients need treatment. Over 3 million Americans have the blood-borne, tough-to-treat disease, which can go undetected for many years until the liver is severely damaged. More people will be diagnosed as the baby boomer generation ages.
After a two-decade drought, the first two new hepatitis C drugs were approved last year: Victrelis from Merck & Co. and Incivek, marketed by partners Vertex Pharmaceuticals Inc. and Johnson & Johnson. Both significantly improve the cure rate over what has long been the standard of care — a mix of injections and pills with nasty, flu-like side effects that takes several months and still doesn't cure many patients.
Last month, Bristol-Myers CEO Lamberto Andreotti said his company has four experimental hepatitis C drugs in development that could be a big improvement over the pills-and-shots regimen. The Bristol compounds might also be combined with those of Inhibitex to produce an even more-effective treatment.
Inhibitex has three experimental drugs in midstage human testing, including INX-189, for treating chronic hepatitis C infections. The other two compounds are FV-100, for reducing the pain caused by shingles, and Aurexis, a biologic antibody-based drugs for treating dangerous staph infections in the blood.
Inhibitex also has other potential hepatitis C treatments in laboratory testing, and has a proprietary technology that it's licensed to Pfizer Inc. for developing a possible staph vaccine.
Friday, February 10, 2012
Barclays analyst on GILEAD and IDENIX....
Original article posted on StreetInsider.com 2/10/12 - This is an article a good friend pointed out to me earlier today. If a combo of one nucleoside inhibitor and ribavirin can become a dominant therapy type for HCV - a virus notorious for excessively high, error-prone replication and an uncanny ability to evade the host immune system - then I'm in. To my mind however, that's either excessively positive thinking or a typo.
Barclays on U.S. Pharma: A New Era for Hep C Therapy - Starts Coverage on GILD & IDIX
Analyst, C. Anthony Butler, said, "The race towards developing the second-generation of direct antivirals (DAAs) may be a dead-heat. By the end of this decade, we believe two dominant therapy types will emerge for hepatitis C (HCV) patients: 1) a combination of a nucleotide polymerase inhibitor (Nuc) and ribavirin; and 2) a cocktail of a nucleotide polymerase inhibitor and one or two DAAs of other mechanisms."
"GILD has leapfrogged competitors through the bold acquisition of Pharmasset, and its stock move (+32.7% YTD vs NASDAQ +11.8%) reflects the market sentiment that GILD is leading the HCV race. We estimate that GILD could capture ~40% of the US HCV market by 2020 and US sales would peak at $2.8B in 2017."
"IDIX needs to find a home for its Nuc IDX184 in order to remain a contender."
Currently, shares of IDIX are trading down 1.25% and shares of GILD are flat on the session.
Barclays on U.S. Pharma: A New Era for Hep C Therapy - Starts Coverage on GILD & IDIX
Analyst, C. Anthony Butler, said, "The race towards developing the second-generation of direct antivirals (DAAs) may be a dead-heat. By the end of this decade, we believe two dominant therapy types will emerge for hepatitis C (HCV) patients: 1) a combination of a nucleotide polymerase inhibitor (Nuc) and ribavirin; and 2) a cocktail of a nucleotide polymerase inhibitor and one or two DAAs of other mechanisms."
"GILD has leapfrogged competitors through the bold acquisition of Pharmasset, and its stock move (+32.7% YTD vs NASDAQ +11.8%) reflects the market sentiment that GILD is leading the HCV race. We estimate that GILD could capture ~40% of the US HCV market by 2020 and US sales would peak at $2.8B in 2017."
"IDIX needs to find a home for its Nuc IDX184 in order to remain a contender."
Currently, shares of IDIX are trading down 1.25% and shares of GILD are flat on the session.
Maketwatch asks "Can Vertex Pharma shares stage a comeback?"
(Posted on Marketwatch 2/10/12). Quick speculative answer to the question, probably not in the near term. The remainder of Vertex's HCV portfolio either is in the latter stages of development and doesn't look like a contender for the 'interferon-free' Holy Grail, or in the case of their nucs, pretty far back in development and to say anything about them at this point would be grossly premature. Incivek sales have slowed more than forecasted for the current months in Q1 2012, although we've a month and a half to see another spike. The best bet for real value is their "ultra-orphan' CF drugs, which are impressive. I can't think of a disease state more deserving of better drugs. The population here is limited however, with the size of the disease state only being a fraction of what it is for HCV. Vertex may have taken this into consideration however, with a whopping price of $300,000 for a course of treatment.)
Can Vertex Pharma shares stage a comeback?
By Val Brickates Kennedy, MarketWatch
BOSTON (MarketWatch) — Can Vertex Pharmaceuticals Inc. shares stage a comeback?
That’s a nagging question for investors, who have watched Vertex’s once-bright star fade as the shares of rival hepatitis C-drug developers turn supernova. But Vertex shares could get a good stoking by mid-year, when the results of three key drug studies are due out.
Vertex’s stock had a banner 2011, its shares propelled to new heights by enthusiasm for its drug Incivek, a treatment for the hepatitis C virus, or HCV, a potentially deadly disease that attacks the liver. The drug belongs to a class of medications known as protease inhibitors that also includes Merck & Co. new HCV drug Victrelis.
In recent months, however, investor faith in Incivek’s long-term marketability has been deeply shaken by positive news about rival HCV drugs in development, particularly those in a class of drugs known as nucleotides, or “nukes.”
As a result, shares of Vertex swung from a 52-week peak of $58.87 in mid-May 2011, to a low of $26.50 by late November, when Gilead Sciences Inc. GILD +0.28% announced it was buying nuke-drug developer Pharmasset Inc. for $11 billion, a move that further underscored the perceived value of nuke drugs. Read more on M&A among HCV drug makers.
Over the past couple of months, the stock has managed to climb back into the upper $30s, due largely to anticipation ahead of the expected approval of the company’s drug Kalydeco. A novel treatment for the genetic disease cystic fibrosis, or CF, Kalydeco won approval earlier this month.
What’s still haunting the stock, say analysts, is concern about how well Incivek sales will hold up when the first nuke drugs hit the market and how well Vertex will be able to build-out its HCV and CF franchises.
With key clinical data for both drug programs looming on the horizon, many analysts have taken a wait-and-see approach to the stock. According to FactSet, the average analyst rating currently for Vertex is overweight, with a price target of just over $46 a share.
Two upcoming events, however, could give the shares a needed jolt.
The first is the expected release of early clinical data for two HCV nuke drugs that Vertex is co-developing with Alios BioPharma. The data is expected in the second quarter.
“Vertex’s HCV franchise is quickly becoming obsolete; to stay in the race, Vertex has to develop all oral, pan-genotypic combinations as quickly as possible, and the Alios nukes are the key to such hope,” wrote William Blair analyst Katherine Xu in a recent note about the significance of the data.
Xu recently lowered her price target for Vertex to $44 from $45, citing slower than expected sales of Incivek, but maintained her buy rating on the stock.
The second set of data, which involves the company’s CF drugs, could be the real market mover, however.
“Positive results in CF could get the stock moving again,” said Needham & Co. analyst Alan Carr, who also has a hold rating on the stock.
The CF data will be from a Phase II trial that is testing Kalydeco, which is only approved for use in CF patients with a rare gene mutation called G551D, or about 4% of CF patients, with another experimental CF drug dubbed VX-809.
Vertex is banking that the Kalydeco/VX-809 combo can successfully treat patients with the F508del gene mutation, which is carried by up to 90% of all CF patients. The data is expected mid-year.
Kalydeco, by the way, isn’t cheap. At nearly $300,000 a year, it ranks as one of the most expensive drugs on the market. It’s high price is due in part to its regulatory status as an “ultra-orphan” drug. The regulatory designation is designed to encourage the development of drugs for life-threatening and extremely rare conditions by offering certain financial incentives, such as market exclusivity.
Carr said that even with its current narrow prescribing indication, Kalydeco could reach peak sales of $1 billion a year. Even if Vertex were forced to lower the price of the product, which would like happen if it were approved for a much larger patient population, sales could still be in the billions.
“According to our probability-adjusted net present value model, for every 10% increase in the probability of success for the combo, Vertex’s stock will have $4-$5 per share in upside, representing a powerful lever,” wrote Xu, of the CF drugs.
“We believe there is a good chance for the Phase II combo data to be successful, which may compensate for the decline of the HCV franchise and lead to the next leg of growth for Vertex,” Xu added.
That said, the Kalydeco data may also prove to be a bust. Data from an earlier segment of the Phase II trial showed the combination to be only modestly effective. Vertex is hoping that data from a second segment of the trial, which is administering VX-809 in higher doses over a longer period of time, yields more impressive results.
“People are getting pretty excited, but I’m just not there yet,” said JMP Securities analyst Liisa Bayko in a recent interview. Bayko currently has a hold rating on the stock.
Val Brickates Kennedy is a reporter for MarketWatch in Boston.
Can Vertex Pharma shares stage a comeback?
By Val Brickates Kennedy, MarketWatch
BOSTON (MarketWatch) — Can Vertex Pharmaceuticals Inc. shares stage a comeback?
That’s a nagging question for investors, who have watched Vertex’s once-bright star fade as the shares of rival hepatitis C-drug developers turn supernova. But Vertex shares could get a good stoking by mid-year, when the results of three key drug studies are due out.
Vertex’s stock had a banner 2011, its shares propelled to new heights by enthusiasm for its drug Incivek, a treatment for the hepatitis C virus, or HCV, a potentially deadly disease that attacks the liver. The drug belongs to a class of medications known as protease inhibitors that also includes Merck & Co. new HCV drug Victrelis.
In recent months, however, investor faith in Incivek’s long-term marketability has been deeply shaken by positive news about rival HCV drugs in development, particularly those in a class of drugs known as nucleotides, or “nukes.”
As a result, shares of Vertex swung from a 52-week peak of $58.87 in mid-May 2011, to a low of $26.50 by late November, when Gilead Sciences Inc. GILD +0.28% announced it was buying nuke-drug developer Pharmasset Inc. for $11 billion, a move that further underscored the perceived value of nuke drugs. Read more on M&A among HCV drug makers.
Over the past couple of months, the stock has managed to climb back into the upper $30s, due largely to anticipation ahead of the expected approval of the company’s drug Kalydeco. A novel treatment for the genetic disease cystic fibrosis, or CF, Kalydeco won approval earlier this month.
What’s still haunting the stock, say analysts, is concern about how well Incivek sales will hold up when the first nuke drugs hit the market and how well Vertex will be able to build-out its HCV and CF franchises.
With key clinical data for both drug programs looming on the horizon, many analysts have taken a wait-and-see approach to the stock. According to FactSet, the average analyst rating currently for Vertex is overweight, with a price target of just over $46 a share.
Two upcoming events, however, could give the shares a needed jolt.
The first is the expected release of early clinical data for two HCV nuke drugs that Vertex is co-developing with Alios BioPharma. The data is expected in the second quarter.
“Vertex’s HCV franchise is quickly becoming obsolete; to stay in the race, Vertex has to develop all oral, pan-genotypic combinations as quickly as possible, and the Alios nukes are the key to such hope,” wrote William Blair analyst Katherine Xu in a recent note about the significance of the data.
Xu recently lowered her price target for Vertex to $44 from $45, citing slower than expected sales of Incivek, but maintained her buy rating on the stock.
The second set of data, which involves the company’s CF drugs, could be the real market mover, however.
“Positive results in CF could get the stock moving again,” said Needham & Co. analyst Alan Carr, who also has a hold rating on the stock.
The CF data will be from a Phase II trial that is testing Kalydeco, which is only approved for use in CF patients with a rare gene mutation called G551D, or about 4% of CF patients, with another experimental CF drug dubbed VX-809.
Vertex is banking that the Kalydeco/VX-809 combo can successfully treat patients with the F508del gene mutation, which is carried by up to 90% of all CF patients. The data is expected mid-year.
Kalydeco, by the way, isn’t cheap. At nearly $300,000 a year, it ranks as one of the most expensive drugs on the market. It’s high price is due in part to its regulatory status as an “ultra-orphan” drug. The regulatory designation is designed to encourage the development of drugs for life-threatening and extremely rare conditions by offering certain financial incentives, such as market exclusivity.
Carr said that even with its current narrow prescribing indication, Kalydeco could reach peak sales of $1 billion a year. Even if Vertex were forced to lower the price of the product, which would like happen if it were approved for a much larger patient population, sales could still be in the billions.
“According to our probability-adjusted net present value model, for every 10% increase in the probability of success for the combo, Vertex’s stock will have $4-$5 per share in upside, representing a powerful lever,” wrote Xu, of the CF drugs.
“We believe there is a good chance for the Phase II combo data to be successful, which may compensate for the decline of the HCV franchise and lead to the next leg of growth for Vertex,” Xu added.
That said, the Kalydeco data may also prove to be a bust. Data from an earlier segment of the Phase II trial showed the combination to be only modestly effective. Vertex is hoping that data from a second segment of the trial, which is administering VX-809 in higher doses over a longer period of time, yields more impressive results.
“People are getting pretty excited, but I’m just not there yet,” said JMP Securities analyst Liisa Bayko in a recent interview. Bayko currently has a hold rating on the stock.
Val Brickates Kennedy is a reporter for MarketWatch in Boston.
Thursday, February 9, 2012
Open Invitation to the 2nd World Congress on Virology...
Click here for full information.
2nd World Congress on Virology is expected to bring the elite class of virologists and potential vaccine developers to share their eminent thoughts and experiences. Be there to witness some of the breakthroughs in field of virology.
At the successful meet of 1st International conference where researchers and developers converged to deliver their ideas and shared their experiences and breakthroughs. This event offered a platform to share technological advances and collaborations from different disciplines of virology, advances in public healthcare and for the socio economical development of society.
Virology-2012 highlights the following topics:
• HIV Research • Agriculture Virology
• Epidemic studies • Animal Virology
• Influenza Viruses • Drug discovery program
• Hepatitis Research • Anti Viral and Retro-viral drugs and therapy
• Tumor Virology • Anti Viral Vaccine development
To Collaborate Scientific Professionals around the World
Dates of the Conference: 20-22 August 2012
Venue of the Conference: Renaissance Las Vegas Hotel, USA
Theme: Innovations and Therapeutic approaches in Virology
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