Canadian Association of Hepatology Nurses (CAHN) speak on HCV treatment and patient care.....

Media Advisory posted on 4/30/12 on MarketWatch.com. If there is one thing I can take out of my long exposure to the virology medical space, it's that nurses, nurse practioners and physician assistants are the true unsung heroes of HCV care. More than not, it's these providers that are doing the heavy lifting - fielding call backs, managing adverse events, ensuring patients are compliant to difficult regimens as well as managing clinical trials. They are medical personnel, cheerleader and social support system all rolled up into one.  It's nice to see groups form on the basis of specialty to trade best practices and market themselves, such at the Canadian Association of Hepatology Nurses (CAHN). I hope they get the media attention they truly deserve. 

April 30, 2012, 7:00 a.m. EDT
Media Advisory - Interview Local Nurses Dedicated to the Hepatitis C Community: National Nursing Week - May 7 to 13, 2012

TORONTO, April 30, 2012 /PRNewswire via COMTEX/ -- During National Nursing Week, Canadians will recognize and celebrate the important contributions nurses make daily to patient care in Canada. The role nurses play in the prevention and management of chronic hepatitis C, a potentially life-threatening virus, provides a powerful example of their impact as supporter, educator and counsellor.

Canadians living with chronic hepatitis C often fear the judgment of others because the virus infecting them is often associated with injection drug use. The reality is that people can contract the virus through a number of different ways including, body piercings, tattoos, blood transfusions or personal care items (razors).

Members of the Canadian Association of Hepatology Nurses (CAHN) build trusted relationships with patients by not focusing on how the hepatitis C virus was contracted, but rather on providing care and support that is beneficial, respectful and can lead to a cure.

The road to a cure is a difficult journey for patients living with chronic hepatitis C. While treatments can be very successful at getting rid of the virus, the stigma associated with the disease often requires patients to struggle through chemotherapy-like side effects in isolation.

CAHN wants to shatter the stigma for those people living with chronic hepatitis C by helping Canadians recognize that anyone, including someone they know and love, could be living with this virus. Stigma must not be a barrier to detection and treatment.

This National Nursing Week, celebrate the leadership provided by CAHN nurses in the prevention and management of chronic hepatitis C.

What: Interview opportunities with nurses and individuals living with chronic hepatitis C willing to share their stories Who: Cheryl Dale, President of the Canadian Association of Hepatology Nurses, CAHN members and individuals living with chronic hepatitis C Where: The following communities across Canada: Ontario (Toronto, Oakville, Mississauga, Guelph, Hamilton, Kitchener-Waterloo, Newmarket, Sutton, Sudbury, North Bay, and London), Quebec (Montreal), British Columbia (Vancouver, Kelowna, and Nanaimo), Alberta (Edmonton), Nova Scotia (Halifax), and Saskatchewan (Prince Albert) When: National Nursing Week (May 7-13, 2012)

SOURCE Canadian Association of Hepatology Nurses

Copyright (C) 2012 PR Newswire. All rights reserved

JMP Securites upgrades Idenix stock on HCV pipeline...

Posted on 4/30/12 on CBSNews.com. JMP Securities analyst Lisa Bayko doesn't think much of Idenix's nucleotide inhibitor IDX 184 (recently given the green light from the FDA after a clinical hold) but has higher hopes for compounds deeper in the Idenix pipeline. Specifically, she mentions NS5A inhibitor IDX 719 which Idenix currently retains ownership of.  

April 30, 2012 3:15 PM

Idenix Pharmaceuticals rises on analyst upgrade

NEW YORK — Shares of Idenix Pharmaceuticals Inc. rose Monday after a JMP Securities analyst upgraded the stock, saying it should trade higher as Idenix reports new data on its experimental hepatitis C drugs.

THE SPARK: Analyst Liisa Bayko upgraded the shares to "Market Perform" from "Market Underperform." Bayko said she doesn't think the company's most advanced drug candidate is effective enough to be the basis of a new treatment for the virus, but had a more optimistic view of some of Idenix's other drug candidates.

"We expect a steady flow of news from Idenix's hepatitis C pipeline in the second half of 2012 to generate increased interest in the stock," she wrote.

THE BIG PICTURE: Idenix is paid royalties on sales of the hepatitis B drug Tyzeka, which is marketed by Swiss drugmaker and Idenix shareholder Novartis AG. Idenix's most advanced drug candidate is designated IDX184. That drug is currently in mid-stage clinical testing. In January, the company started an early-stage trials of a drug candidate called IDX719.

Novartis has an option to license IDX719, but Bayko said she thinks Novartis will decline. That would give Idenix full control of the drug, and it would be able to combine IDX719 with other experimental drugs and look for another development partner.

SHARE ACTION: Idenix stock rose 29 cents, or 3.4 percent, to $8.84 in afternoon trading, after peaking at $9.21 during the session. The shares are down 44 percent from their 52-week high of $15.25, which they set Jan 19.

Duke University program integrates Hepatitis C and alcohol addiction treatment...

Posted 4/26/12 on the Center for Health Policy & Inequities Research at Duke University website. This is just all-around good stuff - A Duke study published in the April issue of  the journal 'Digestive Diseases and Sciences' shows some positive outcomes in getting Hepatitis C patients to stop or significantly cut down alcohol consumption while on treatment. This integrative model pairs both a Hepatologist and an Addiction Specialist and serves as a template on which to base similar programs.  For the six month program, 44% of patients stopped drinking alcohol by the end of the period and those that didn't stop, reduced consumption by 30%.  Long term follow-up will be needed, but this data seems promising. 

Integrated Health Care Model Shows Promise for Hepatitis C Patients in Durham

Posted by Anna Both on Apr 26, 2012 in Faculty, Rae Jean Proeschold Bell, Research
Reported by the Duke Global Health Institute:

Four in ten hepatitis C patients who drank alcohol refrained from it as part of a Duke pilot program that integrates alcohol and hepatitis C treatments. Led by DGHI researcher Rae Jean Proeschold-Bell and Duke physician Andrew Muir, the dual model of care may be a viable option for steering these patients away from alcohol, who may otherwise develop serious health complications that lead to liver failure or death.

The Duke study, featured in the April issue of Digestive Diseases and Sciences, involved hepatitis C patients from the Duke Liver Clinic who received both alcohol treatment and medical care over a six-month period. Of the 53 alcohol-drinking patients in the study, 44 percent had stopped drinking alcohol by the end of the six months. Patients who did not become abstinent by six months still reported a 30 percent drop in alcohol consumption, spending on alcohol and urges to drink.

“We were able to show that integrated hepatitis C-alcohol care is feasible,” said Proeschold-Bell, a DGHI faculty member at the Center for Health Policy and Inequalities Research. “More than that, the study shows that such integrated care results in alcohol reductions that benefit patient health.”

Researchers say the intervention worked in part because it focused on liver health, rather than simply reducing alcohol use. It involved weekly group therapy and bi-weekly individual sessions customized to each patient that address alcohol use, nutrition, stress and family support. Because knowledge alone does not change behavior, the addictions specialist taught patients practical ways to improve other aspects of their lives based on their individual circumstances.  Study participants were also evaluated for mental illness and had access to a psychiatrist for care, if needed.

The research team also found ways to increase communication and collaboration between the patient’s hepatologist and addictions specialist, a critical part of the study.

“We didn’t know the extent to which we could get busy medical providers and addictions specialists to collaborate. We had to find ways to fit the collaboration into the clinic flow,” said Proeschold-Bell. “In some instances, we had the addictions specialist use a laptop outside the patient exam rooms so medical providers could easily access her and her knowledge about the patient’s alcohol use and behavior changes.”

To date, studies have shown that adults with hepatitis C are three times more likely to have at least one alcoholic drink a day and almost eight times more likely to have at least three drinks a day, compared to adults without hepatitis C.  The combination of alcohol use and hepatitis C speeds the time to liver failure and increases rates of liver fibrosis and cancer.

As strong proponents of clinic-based alcohol treatment, Proeschold-Bell and Muir hope to pursue a larger study that recruits patients from the Duke Liver Clinic, the UNC Liver Clinic and the Durham Veterans Affairs Medical Center.

“Alcohol treatment needs to occur in a trusted and known setting,” said Muir.  “This study shows that patients will attend alcohol treatment offered in the liver clinic setting and try to change their behaviors in the context of their lives beyond alcohol use.”

J&J open to partnering with Vertex in HCV drug development...

Posted on 4/20/12 on Bloomberg.com. The growing body of evidence in HCV drug development suggests that alliances are important (unless you happen to be Gilead) especially with partners that are owned by deep-pocketed, well diversified organizations like Johnson and Johnson.  Hopefully J&J can put back some luster on Vertex's non-nuc VX-222. Actually, despite it's inherent relative lower barrier of resistance, it's a good drug - QD dosing, pretty powerful, clean and low potential for drug interactions. Just needs the right partners in a regimen. TMC435 may be one of 'em - QD dosing, powerful, no need for ritonavir and thus no ritonavir baggage - sounds good on paper, anyway. 


J&J Open to Expanding Hepatitis C Cooperation With Vertex
By Makiko Kitamura - Apr 20, 2012 8:09 AM PT

Johnson & Johnson (JNJ)’s Janssen unit said it may explore widening cooperation on hepatitis C with Vertex Pharmaceuticals Inc. (VRTX) that may develop in tandem with a separate partnership with Medivir AB (MVIRB) on the disease.

“We remain open to see if we can expand our collaboration,” Gaston Picchio, vice president of Janssen’s global clinical virology and hepatitic disease area, said in an interview today in Barcelona, where he’s attending the European Association for the Study of the Liver annual meeting. “Vertex has announced plans for developing interferon-free therapies. We are partners, so that puts us in a better position to be a part of that,” should studies prove to be promising.

Vertex said on April 18 that it will start enrolling patients in a mid-stage study combining three medicines, excluding interferon, a core component of the current standard of care. Vertex and competitors including Gilead Sciences Inc. (GILD), Bristol-Myers Squibb Co. (BMY) and Abbott Laboratories (ABT) are racing to develop next-generation treatments for hepatitis C that exclude interferon because of flu-like side effects.

Vertex and J&J collaborated to develop telaprevir, marketed as Incivek by Vertex in North America and as Incivo by Janssen in other regions including Europe. The drug was approved by regulators last year as a treatment for hepatitis C in combination with interferon and ribavirin.
Medivir Project

J&J, which has its headquarters in New Brunswick, New Jersey, is also developing the protease inhibitor TMC435 with Huddinge, Sweden-based Medivir, which has said mid-stage trials of the drug in interferon-free combinations with Gilead’s 7977 and with Bristol-Myers’s daclatasvir experimental drugs are starting in the second quarter.

While J&J and Medivir are also developing the TMC647 polymerase inhibitor, Vertex’s VX-222 compound in the same class of drugs is further along in development. VX-222 is one of the three drugs included in Cambridge, Massachusetts-based Vertex’s mid-stage interferon-free treatment study.

Meanwhile, J&J is also “committed” to improving the labeling of Incivo by conducting further trials that examine less frequent dosage as well as efficacy in patients also infected by the HIV virus and those who have had liver transplants, Picchio said.

To contact the reporter on this story: Makiko Kitamura in Barcelona via mkitamura1@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

'The Street' grades the HCV players post-EASL...

The Street's Nathan Sadeghi-Nejad grades the stocks of the big players in HCV post-EASL.  It's a good read, much better than those of his peers, although my opinion on certain topics differs from his in some respects. It's helpful to know that Mr. Sadeghi-Nejad's perspective is from one entrenched in the investment community, a community notorious for knee-jerk reactions to data deemed good or bad simply based on numbers in interim data.  The result is often either 'irrational exuberance' or 'irrational discouragement' causing wild fluctuations in stock price.  Greater scrutiny must often be utilized to get the 'real story' behind the numbers - patient demographics, fibrosis scores, BMI, trial structure, population size, P values, etc.  This is not to devalue the investment community but a call for a more discriminating eye when it comes to data analysis.  Mr. Sadeghi-Nejad's analysis shows a surprising amount of discrimination. My opinion does differ from his in respect to a couple of things (he's awfully hard on Achillion, doesn't mention BI or Merck and... well, see below).


I'll go on record to challenge Mr. Sadeghi-Nejad's claim that interferon is 'dead'. That's a pretty dimissive statement. While interferon-free therapies may be an option for many patients, especially those that are treatment naive, genotype 1b, 2, 3 and 4, with moderate fibrosis, with IL28B CC/TC status. However interferon will most likely play a large role in the 'difficult to treat' population - patients presenting with advanced fibrosis/compensated cirrhosis, genotype 1a, steatosis and IL28B TT status and/or a majority of null-responders.  


In fact, the data from BMS/s EMERGE trail - a head-to-head trial looking at PEG-Lambda + ribavirin vs PEG-interferon-alfa + ribavirin - was horribly under-appreciated. Not only was PEG-Lamda a good deal more effective at achieving SVR than PEG-alfa, there were also significantly less side effects.  We need to see how PEG-Lambda performs with the 2nd and 3rd generation DAAs in these difficult to treat patient populations. There is definitely a need as these patients are most at risk for developing decompensated liver disease and HCC. 


OK, off my soapbox now. 


BARCELONA (TheStreet) -- Wow, it's been a busy few days at the European Association for the Study of the Liver (EASL) annual meeting in this beautiful Catalan capital. Investors obsessed with emerging hepatitis C therapies had plenty of new data to analyze.

Let me make one general observation about the future of hepatitis C treatment before I recap and grade each of the companies with a significant presence at the EASL meeting. Interferon -- the injectable immune system booster saddled with troublesome side effects -- is dead. The future of hepatitis C therapy belongs to interferon-free regimens. Physicians at the conference talked about interferon as if it were invented in medieval times. It's clear that any company seeking a role in hepatitis C going forward must develop or acquire an effective interferon-free regimen or face irrelevance.


Let's move to the winners and losers of EASL 2012.

Gilead Sciences(GILD_):

Grade: A-

Gilead was the big story of the conference. The company emphatically reclaimed the driver's seat in HCV, at least for now, with a combination of solid scientific results and ruthless, strategic maneuvering.

In a crowded Thursday session, anxious Wall Streeters awaited new data for Gilead's GS-7977, a once-daily nucleotide polymerase inhibitor, or "nuc." Despite impressive early data -- which prompted the undeniably expensive $11 billion Pharmasset acquisition -- subsequent results from a GS-7977 trial called ELECTRON showed the drug to have little effect in "null" responders and generated lots of investor anxiety. I was no exception. Despite my favorable disposition towards GS-7977, I wanted confirmation of the early data; most investors I spoke with shared my view.

We got what we were looking for.

An impressive 88% of treatment-naive patients in ELECTRON achieved sustained virologic response four weeks after stopping treatment (an early indication of "cure" known as SVR4) with 12 weeks of GS-7977 and ribavirin (RBV), a companion drug used in hepatitis C. Expectations leading into EASL were for an SVR4 of 70%.

At the same time, Gilead issued a press release containing preliminary data from QUANTUM, an ongoing study in treatment-naive patients also using the GS-7977 plus ribavirin combination therapy. The SVR4 rate in this study was 59%, lower than ELECTRON due to enrollment of more difficult-to-treat patients. [84% of QUANTUM patients had unfavorable "non-CC" genetics, versus 56% in ELECTRON.]

Results from the ELECTRON AND QUANTUM studies of GS-7977 were important but not the star of EASL. What got everyone really excited were data from the mid-stage study combining GS-7977 with Bristol-Myer Squibb's(BMY_) NS5A replication complex inhibitor daclatasvir. Among the patients with genotype 1 hepatitis C, GS-7977 plus daclatasvir resulted in an SVR4 rate of 100%. Yes, the combination therapy cured all treated patients. These data literally elicited high fives from several of the generally reserved hedge fund analysts in attendance. It's hard to argue with an SVR4 of 100%, but longer-term follow-up data are needed to confirm these results. Physicians traditionally use SVR12 (12 weeks) or SVR24 (24 weeks) as a final indication of cure, although recent data show a strong correlation between SVR4 and later follow up assessments.

As if that weren't enough excitement, Gilead also generated some drama at the meeting -- and elicited a "patients-not-profits" rebuke from my colleague Adam Feuerstein -- when word got out that the company had refused an offer from Bristol-Myers to collaborate on further development of GS-7977 and daclatasvir. Although Gilead insists it hasn't made a final decision, I'm guessing management will try to combine GS-7977 with GS-5885, an early-stage drug candidate in the same NS5A class as daclatasvir. Obviously, Gilead wants to keep all the profits from a highly potent, all-oral hepatitis C therapy for itself.

In GS-7977, Gilead appears to control a strong, future "backbone" for any next-generation hepatitis C regimen. I have mixed feelings about Gilead's apparent desire to deny Bristol-Myers access to the drug and therefore prevent a daclatasvir-GS-7977 regimen from reaching the market. Patients and their advocates will probably be justifiably upset that such this apparently highly effective regimen won't be developed further. I understand that. Interestingly, physicians I spoke with at the meeting didn't care either way. That surprised me; I would have expected more complaints.

As an investor, I don't fault Gilead for angling to maximize profits -- I've never subscribed to the biotechnology industry's cloying "patients first" rhetoric. However, the move does increase the company's clinical risk in hepatitis C. Even though initial GS-5885 data look clean, a problem could still emerge and daclatasvir is far more established. Essentially, management is betting that the promise (and eventually, the reality) of an "all Gilead" HCV regimen outweighs additional R&D expenses and near-term clinical risks.

That seems like a reasonable bet, and I think the stock will continue to work -- Gilead is still only trading at around 13 times estimates 2012 earnings.

Bristol-Myers Squibb:

Grade: C

Bristol-Myers had quite the Dickensian conference. The company's daclatasvir plus Gilead's GS-7977 wowed investors and physicians alike. The best of times!

Unfortunately, Gilead doesn't want to partner GS-7977; the non-nucleoside polymerase inhibitor BMS-791325 seems only modestly effective and may have toxicity issues; the protease inhibitor asunaprevir has a messy side effect profile; and adverse event rumors are haunting BMS-986094 (formerly known as INX-189), the "nuc" obtained via the $2.5 billion purchase of Inhibitex. Oh, and brivanib fails in liver cancer. The worst of times!

Gilead's refusal to collaborate raises an important observation. Consider this: Bristol-Myers hasn't made public much data about BMS-986094 since closing the Inhibitex acquisition and non-specific toxicity rumors dogged the drug at EASL. Does this explain why Bristol-Myers is trying to pressure Gilead into moving the daclatasvir-GS-7977 regimen into phase III trials? Put another way, if Bristol-Myers was confident that BMS-986094 (INX-189) could easily replace GS-7977 in a combination regimen with daclatasvir, why not play the same ruthless, "winner take all" game as Gilead?

If I was a Bristol-Myers bull, I would be worrying about the future of BMS-986094 (INX-189.)

Management better hope it can either woo or shame Gilead into collaboration (unlikely, unless something goes wrong with GS-5885) or that the Inhibitex drug plays nice with daclatasvir and the toxicity rumors are false. Otherwise, Bristol-Myers will have to open up the M&A wallet again to remain relevant in the race for next-generation hepatitis C therapies.

Abbott(ABT_):

Grade: B

Despite Wall Street skepticism, I think Abbott remains firmly in the hepatitis C game. The company presented data from two major studies, PILOT and CO-PILOT, in late-breaker sessions on Saturday afternoon.

PILOT enrolled treatment-naive patients to receive 12 weeks of ABT-450 -- a protease inhibitor that requires blood-level "boosting" with ritonavir -- in combination with the non-nucleoside NS5B polymerase inhibitor ABT-072 and ribavirin. It must be noted that all patients had favorable "C/C" genetics, making it an easy group to treat. Nonetheless, Abbott reported an impressive 91% SVR24.

One patient in PILOT suffered a late relapse after 36 weeks of follow up which dropped the SVR36 "cure" rate to 82%. These are some of the longest follow-up results yet with next-generation, all-oral regimens so the relapse was noteworthy. I'm not sure if the relapse is an isolated event, and no one I spoke with had a definitive answer. Keep the question of whether interferon-free regimens might leave patients more susceptible to late relapse in mind -- it needs to be watched closely going forward.

In Abbott's second CO-PILOT study, patients received 12 weeks of ritonavir-boosted ABT-450 and the "non-nuc" ABT-333. Patients in the two treatment-naive arms achieved SVR12 rates of 93% and 95% (These patients were a mix of easy- and hard-to-treat patients more comparable to competitors' studies). I was impressed with these data, as were most physicians at EASL. A third arm in the CO-PILOT study enrolled "non-responders" but generated only a 47% SVR12; these patients need a more robust regimen.

The downside to the CO-PILOT regimen is complexity: ABT-450 is administered once daily, as is ribavirin and ritonavir, whereas ABT-333 is dosed twice daily. Further, ritonavir has numerous drug-drug interactions. Physicians I spoke with at EASL were mixed about whether or not patients could be sufficiently compliant in the real-world setting. I doubt it. Abbott plans to co-formulate future combinations, which will include other drugs (the company also has a NS5A inhibitor.)

I plan on taking a closer look at Abbott in a future column. The company is highly dependent on sales of the rheumatoid arthritis drug Humira, which I don't like, but investors aren't assigning much value to its hepatitis C assets. Based on what I saw at EASL, that could be a mistake.

Idenix Pharmaceuticals(IDIX_):

Grade: B-

Despite having no data at EASL this year, Idenix will likely benefit from the rising tide created by Gilead and Bristol-Myers. After successfully negotiating side effect questions and a partial clinical hold, Idenix has emerged as the only smallish biotech company with both a "nuc" (IDX-184) and an NS5A inhibitor (IDX-719.) By year-end, we will see SVR4 data for IDX-184 combined with interferon and ribavirin; and early data on IDX-719.

If these results look promising, Idenix is going to be hugely attractive to large pharma companies with lackluster hepatitis C programs and an urge to catch up. Novartis(NVS_) already has a first right to license IDX-719 by year-end, but other companies might be interested regardless of the Swiss pharma giant's decision. I would be a buyer of Idenix, but keep any position on the small side.

Achillion Pharmaceuticals(ACHN_):

Grade: C-

Meh. Achillion has two NS5A inhibitors, ACH-3102 and ACH-2928, which look okay in early studies, but I'm not sure what makes these drug candidates stand out. I feel similarly unexcited about ACH-1625, a protease inhibitor, which looked decent in a confusing study that combined it with interferon and ribavirin. I'm just not convinced these are valuable assets, so I'm going to wait on the sidelines.

Vertex Pharmaceuticals(VRTX_):

Grade: D-

Out of sight, out of mind. The big loser of the EASL conference was Vertex Pharmaceuticals. The company's first-in-class protease inhibitor Incivek pioneered treatment with direct-acting antivirals in hepatitis C, but the drug now feels woefully outdated less than one year after approval. The problem is that Incivek therapy still requires patients to receive weekly injections of interferon. Remember what I noted at the top of this column -- interferon is dead -- so any drug attached to interferon is at risk of the same fate.

Vertex does have ongoing interferon-free studies that combine Incivek with ribavirin and VX-222 -- an earlier-stage "non-nuc" drug candidate -- but the combination seems like a long shot. Earlier this year, the company reported that 82% of patients in the Phase II ZENITH trial achieved an SVR4. Vertex also added to its hepatitis C portfolio recently, acquiring two "nucs" through a partnership with Alios BioPharma. Unfortunately, those compounds do not yet have any clinical data and are substantially behind the market leaders.

More from Nathan Sadeghi-Nejad
Calling Shenanigans on Amylin PharmaGilead And The Future of HIV TherapyRegeneron, Amgen And The 'Hope Creation Cycle"
Market Activity
Vertex Pharmaceuticals| VRTX
Gilead Sciences Inc| GILD
Achillion Pharmaceuticals Inc.| ACHN
Meanwhile, I expect already flat Incivek sales will decline rapidly as physicians urge patients to defer treatment until next-generation drugs reach the market. Street estimates now reflect a sequential decline in Incivek sales. If Vertex isn't able to expand use of the cystic fibrosis drug Kalydeco to a broader group of patients at premium pricing, Vertex might be a short. (I haven't done enough work to have a final opinion yet.) Either way, this wasn't a good EASL meeting for the Boston-based biotech.

Onyx Pharmaceuticals(ONXX_):

Grade: B+

EASL is not only about hepatitis C. This is a meeting that covers all liver disease, which includes liver cancer. In this regard, Onyx emerged from EASL a solid winner even though the company presented no new data.

Some investors expected positive results from a 395-patient trial of Bristol-Myers' brivanib in late-stage liver cancer. Positive brivanib data would have been bad news for Onyx, whose key asset, Nexavar, dominates the liver cancer treatment market and faces no major competitors. Fortunately, brivanib proved both a dud and a point.

In a crowded Saturday session, the same investigator who led Onyx's Phase III study presented findings from Bristol-Myers' BRISK-PS, which randomized patients who had progressed on, or were intolerant of, Nexavar to receive either brivanib or placebo. Despite positive response rate (12% versus 2%) and time to progression (4.2 months versus 2.7 months) data, brivanib showed only a slight survival benefit (9.4 months versus 8.2 months). For comparison, Nexavar improved survival by 2.8 months in the Phase III SHARP trial that led to the drug's approval.

Before I get a slew of comments on the value of any benefit in this difficult-to-treat disease, I would note that the data were not even close to statistical significance and brivanib caused meaningful toxicity, including six patient deaths attributed to the drug by study investigators.

The key takeaway here -- other than that Nexavar's leading position in liver cancer remains safe -- is that surrogate endpoints like response rate and progression-free survival do not always correlate with a survival benefit. This is particularly true in studies of solid tumors. Despite what feels like the constant media coverage of emotional demands for quick approvals based on limited data, the BRISK-PS data once again highlight the need for companies to conduct randomized studies using real endpoints.

Whew. That does it for EASL 2012, but my travels continue. This afternoon I'm off to Boston to surprise Mom for her birthday. (Let's see if she reads all the way to the end of my columns.)

Happy birthday Mom!

Disclosure: Sadeghi has no positions in any of the stocks mentioned in this article.

Presidio Pharmaceuticals announce new HCV pan-genotypic non-nuc polymerase inhibitor....

Posted on MarketWatch, 4/21/12.  Presidio releases pre-clinical profile of it's new novel pan-genotypic non-nuc polymerase inhibitor PPI-393 at EASL. It will be a very competitive environment for HCV drugs just getting started in development given the high bar set with interim SVR data presented for the 2nd generation HCV drugs at EASL.  New drugs in development will have to offer a significant advantage in respect to resistance profile, dosing, tolerability and efficacy to compete. 

PRESS RELEASE

April 21, 2012, 2:00 a.m. EDT

Presidio Pharmaceuticals Announces a New Clinical Candidate, PPI-383, a Novel Pan-Genotypic Non-Nucleoside Polymerase Inhibitor for HCV

Pre-Clinical Profile to be Presented at the 47th European Association for the Study of the Liver (EASL) Meeting

SAN FRANCISCO, Apr 21, 2012 (BUSINESS WIRE) -- Presidio Pharmaceuticals, Inc. announced today that PPI-383, a novel non-nucleoside polymerase inhibitor to treat hepatitis C virus (HCV), has been nominated for clinical development and will be profiled by Richard Colonno, Ph.D., Chief Scientific Officer, in poster 1173 at the 47th Annual EASL meeting being held in Barcelona, Spain on April 21st, 2012.

PPI-383 is a potent, pan-genotypic inhibitor of HCV discovered at Presidio, which exhibits a favorable pharmacokinetic and safety profile in multiple animal species following oral dosing. PPI-383 binds to the Palm II pocket of the HCV polymerase (NS5B) and possesses excellent biochemical and pharmaceutical properties critical to successful drug development, including a potential for once-daily oral dosing and minimal potential for drug-drug interactions. PPI-383 is currently undergoing further preclinical evaluation to support initiation of clinical studies alone and in combination with PPI-668 next year.

PPI-383, identified through an extensive medicinal chemistry effort, exhibits EC50s of 8.3 and 2.2 nM in HCV 1a and 1b replicon assays, respectively. PPI-383 is also active against other major HCV genotypes (2a, 3a and 4a) in stable replicon cell assays (EC50s of 4.4-11.7 nM). "The selection of PPI-383 underscores Presidio's continued commitment to generate best-in-class compounds for treating HCV," commented Dr. Colonno, who added, "It is an excellent complement to our lead NS5A inhibitor, PPI-668, currently completing Phase 1b clinical studies. We intend to develop oral, combination regimens that possess potent, pan-genotypic activity." The distinct mechanism of action of PPI-383 will potentially allow its use in combination regimens with all other classes of HCV inhibitors.

Poster 1173, entitled "Identification and Characterization of PPI-383, a Next Generation HCV NS5B Non-Nucleoside Inhibitor with Potent Activity Against all Major HCV Genotypes" will be presented by Dr. Colonno on Saturday, April 21st, 2012 at the Centre Convencions Internacional Barcelona (CCIB) from 8:00 AM to 5:00 PM.

About HCV

Chronic hepatitis C is a persistent, potentially progressive inflammatory liver disease caused by chronic infection with the hepatitis C virus (HCV). Worldwide, there are an estimated 130 to 170 million persons with chronic HCV infection, with over 350,000 deaths occurring each year.

The current standard treatment for hepatitis C in the United States, for patients with HCV genotype-1 infection, is combined administration of pegylated-interferon-alfa, ribavirin, and an HCV protease inhibitor. This multi-drug treatment is characterized by incomplete efficacy for HCV genotype-1 patients, variations in efficacy according to patients' underlying human genetic factors, no established efficacy for patients infected with other HCV genotypes, severe side effects in some patients, and dosing inconveniences. In countries where the current HCV protease inhibitors are not yet regulatory-approved, standard treatment is only pegylated-interferon-alfa plus ribavirin, which is less effective.

There is a continuing need for all oral, more consistently effective and better tolerated antiviral combinations for HCV infection, regardless of HCV genotype, patient genetic factors, or disease stage.

About Presidio

Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics. For more information, please visit our website at: www.presidiopharma.com .

SOURCE: Presidio Pharmaceuticals, Inc

Boehringer Ingelheim presents interferon-free SOUND-C2 data at EASL...

Today (Saturday, April 21, 2012) is the big day all us HCV drug development nerds (I'd use 'wonks', but that sounds even worse) are waiting for in regards to the late-breaker presentations from EASL and any additional nuggets of info.  One of those presentations will  on the SOUND-C2 trial, featuring the interferon-free combination of Boehringer Ingelheim's HCV PI BI 201335 and polymerase inhibitor BI 207127 both with  ribavirin. According to the press release below, the interim results of the combo show a 68% SVR12 overall in genotype 1 patients in the 28 week arm regardless of IL-28B status. In the 16 week arm, SVR12 was achieved in 59% of patients.  As one might suspect, those subjects that were genotype 1a and non-CC IL-28B status experienced higher relapse and breakthrough rates than those who were G1b and CC.  It was also found that without the benefit of ribavirin, the subjects did substantially worse with only at 39% SVR12.  


Details are still coming, but it appears that this will be a 28 week option and the G1a non-CC patients may either need to go longer (there is a 40 week arm of this study that awaits presentation) or the addition of interferon. Ribavirin will clearly be needed in this combination as well. The odds of dosing confusion are a bit higher, with the PI boasting QD dosing and the polymerase inhibitor BID dosing.


A sub-analysis looking at the efficacy of the combination in the compensated cirrhotic was also presented in poster format. Although the numbers are small and clearly the G1b subjects respond better to the combo, it's encouraging to see any sort of SVR12 in this extremely difficult to treat population, especially without the aid of interferon.

Phase 2b Study of Boehringer Ingelheim’s Interferon-Free Hepatitis C Treatment Shows Undetectable Virus in HCV Genotype-1 Patients 12 Weeks After Treatment Ended (SVR12)

Barcelona, Spain and Ridgefield, CT, April 19, 2012 – New data from a pre-specified interim analysis of the Phase 2b SOUND-C2 study show that 68 percent of genotype-1 (GT1) hepatitis C virus (HCV) patients achieved sustained viral response 12 weeks after the end of treatment (SVR12) with Boehringer Ingelheim’s investigational direct-acting antiviral compounds – the protease inhibitor BI 201335 and polymerase inhibitor BI 207127 – plus ribavirin (RBV), without interferon. SVR12 has been highly correlated with SVR24, which is a recognized indicator of viral cure. These patients received combination therapy with BI 201335 once-daily (QD), BI 207127 twice-daily (BID) and RBV for 28 weeks. The SOUND-C2 study investigated interferon-free treatment in HCV GT1 patients, the most difficult genotype to treat, regardless of IL-28B status. Among study participants, 10 percent had compensated liver cirrhosis.

“Eliminating interferon from HCV treatment is an urgent need,” said Stefan Zeuzem, M.D., Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany, and lead investigator of the study. “The antiviral activity of BI's all oral direct-acting antiviral compounds in the SOUND-C2 study demonstrates the potential for an interferon-free cure for HCV.”

Furthermore, a separate arm of the SOUND-C2 study showed that after 16 weeks of interferon-free treatment, SVR12 was achieved in 59 percent of patients. Investigators presented relapse data broken out by genotype and IL-28B status. The rate of relapse in the treatment arms ranged between 2 and 10 percent for GT1b and GT1a-CC patients. There was a higher rate of relapse in GT1a non-CC patients, with relapse ranging from 0 to 40 percent. The full results from this interim analysis of SOUND-C2 are being presented on Saturday, April 21, at the International Liver Congress, the 47th Annual Meeting of the European Association of the Study of the Liver (EASL 2012) in Barcelona, Spain (Abstract #101). These results supplement the abstract findings highlighted today during an official EASL press conference.

“We are looking forward to the final results from this study, that we hope will be a significant step towards an interferon-free future for patients with HCV,” said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “We are committed to the millions of people around the world who are chronically infected with HCV. Through our clinical trial program HCVersoTM, we are working with experts worldwide to ask the difficult questions that remain in HCV to find answers to the challenges that these patients face.”

Planning of the interferon-free Phase 3 clinical trial program is underway.

SOUND-C2 Pre-Specified Interim Analysis
In this open-label Phase 2b study, 362 treatment-naïve GT1 HCV patients were randomized into five interferon-free treatment groups, each with 120 mg BI 201335 QD, but with different dosing of BI 207127 and treatment durations. The randomization was stratified by HCV genotype (1a or 1b) and patient IL-28B genotype, with 41 percent of patients being GT1a and 75 percent being IL-28B CT or TT.

Investigators reported breakthrough broken out by genotype and IL-28B status. In GT1b and GT1a-CC patients, breakthrough occurred in 7 percent of patients in Arm A, 11 percent of patients in Arm B, 19 percent of patients in Arm C, 9 percent of patients in Arm D, and 29 percent of patients in Arm E (no RBV arm). In GT1a non-CC patients, breakthrough occurred in 40 percent of patients in Arm A, 50 percent of patients in Arm B, 25 percent of patients in Arm C, 64 percent of patients in Arm D, and 91 percent of patients in Arm E (no RBV arm).

In this study, the most common adverse events (AEs) were skin (photosensitivity, rash), gastrointestinal (GI) disorders (vomiting, diarrhea), and jaundice due to unconjugated hyperbilirubinemia. Treatment discontinuations due to AEs correlated with increased dosing frequency and treatment duration, with discontinuations ranging from 4.9 percent in Arm A (16 weeks) to 24.7 percent in Arm C (40 weeks). In the arm with BID dosing of BI 207127 (Arm D), discontinuations were 7.7 percent. BID dosing of BI 207127 is planned for Phase 3 investigation.

New York Times on GS-7977 + daclatasvir combo - will it make it to market?

Posted on 4/19/12 via the New York Times. For those of you even casually following the HCV drug development data being presented at EASL, you've no doubt heard that the combination of Gilead's nuc GS-7977 + BMS's NS5A inhibitor daclatasvir wowed just about everyone by reporting 100% SVR in genotype 1 treatment-naive patients with this combination without the support of ribavirin and pegylated interferon. There are certain caveats that I'll go into later regarding the study, but even with those, the results are flat out astounding. The problem appears to be that BMS and Gilead haven't thus far agreed to collaborate on this combination. Gilead seems the most unwilling - they've got their own pipeline of drugs to combine with GS-7977 and their data from GS-7977 + ribavirin garnered an 88% SVR in a similar patient population. With downward pressure on drug costs and and the pressure to increase drug access, it would seem like the more economically appealing option is for Gilead to go to market for the treatment naive population with GS-7977 + a generic drug (ribavirin). After all, 88% SVR with greatly improved tolerability over current therapy with much improved dosing options is nothing to sneeze at. In regards to the tougher-to-treat patients (i.e. null responders, partial responders, advanced fibrosis, steatosis, co-infection), it looks like Gilead  has enough confidence in it's own pipeline and co-formulation ability to not have to rely on the often-difficult-to-manage partnership agreement. No doubt this will be interesting to watch and see what unfolds. 


Collaboration on Hepatitis Drugs Lags
By ANDREW POLLACK
Published: April 19, 2012

A combination of two pills proved extremely effective in treating hepatitis C in a small trial, raising hopes among researchers that the disease will be curable without an injected drug that has debilitating side effects.

David Paul Morris/Bloomberg News

But the combination might not find its way to the market because one pill is owned by Gilead Sciences and the other by Bristol-Myers Squibb. The companies have not agreed to collaborate, to the chagrin of some doctors.

“The only appropriate motivation should be what is the best and fastest way to get cures, not what is best for the shareholders,” said Dr. Scott Friedman, chief of liver diseases at the Mount Sinai School of Medicine in New York, who was not involved in the trial.

Dr. Douglas J. Manion, a senior vice president for Bristol-Myers, said his company was “keen” on working with Gilead but that “thus far, they have been unwilling to engage in that collaboration.”

Norbert W. Bischofberger, executive vice president for research and development at Gilead, said his company wanted to wait several months for data on other treatment options before deciding what path to take.

“We told them it’s too early to jump wildly into this collaboration,” he said.

Both executives spoke separately by telephone from the International Liver Congress in Barcelona, Spain, where data on the drug combination was presented.

Gilead and Bristol are among the leaders of one of the most heated races in the pharmaceutical industry — to develop an all oral treatment for hepatitis C, a liver-damaging virus that infects three million to four million Americans.

New pills introduced last year by Vertex Pharmaceuticals and Merck have sharply improved the cure rate, to about 60 to 80 percent. But those drugs must still be used alpha interferon, which is injected weekly for up to a year and can cause flulike symptoms.

Many companies are trying to develop combinations of pills — similar to those used to treat H.I.V. — that would eradicate the virus without the need for interferon.

Results from several companies presented at the Barcelona conference have given doctors confidence that this will indeed be possible, with the first such combinations reaching the market perhaps by 2014.

Dr. Melissa Palmer, who was a practicing liver specialist until last fall, said that the trials were small and patients were usually not followed long enough to see if they were truly cured.

“It’s going to be important to wait a longer time to see if these results are sustainable,” said Dr. Palmer, who is now a consultant to investors.

Nonetheless, investors were busily predicting from the Barcelona data which companies will capture the billions of dollars a year in possible sales. Besides Gilead and Bristol, some mentioned Abbott Laboratories, which also presented strong preliminary data.

Gilead, a leader in drugs for AIDS, paid $11 billion a few months ago to acquire Pharmasset, based on very preliminary data on its hepatitis drug, now called GS-7977. Subsequent data was not as good and Gilead’s stock sank.

But the data announced on Thursday appeared to restore confidence in 7977. Shares of Gilead gained 12 percent to $52.25. Shares of Bristol rose 1 percent to $33.93.

All 29 of the patients with the strain of the virus that is most common in the United States had no detectable virus in their blood four weeks after finishing 24 weeks of treatment with GS-7977 and Bristol’s pill, daclatasvir. The figure was 28 out of 30 patients with two other virus strains. Each pill was taken once a day.

Doctors usually wait 12 to 24 weeks after finishing treatment to declare a cure, since there can be relapses.

Dr. Bischofberger said that before deciding whether to work with Bristol on a larger trial, Gilead wanted to wait a few months for data showing whether the same two drugs would work with only 12 weeks of treatment instead of 24.

He said he also wanted to see whether Gilead could improve results of using GS-7977 with ribavirin, a drug that is part of the existing treatment.

A combination of GS-7977 with ribavirin, which is generic, would be far less expensive than a combination with daclatasvir, he said, because new hepatitis drugs are expected to cost tens of thousands of dollars for a course of treatment.

A combination with ribavirin would also mean that Gilead would not have to split revenues with Bristol, making it easier to recoup the money it spent to buy Pharmasset.

Dr. Bischofberger said that once both 7977 and daclatasvir won approval, doctors could use them together, so patients would not be shortchanged if the companies did not collaborate.

Gilead interim ELECTRON and QUANTUM SVR4 data...

Posted 4/19/12 on ClinicaSpace.com - Good news for patients, providers and of course Gilead today at EASL. Not so great for interferon, at least regarding it's place in HCV therapy where it increasing looks like it will be niched to specific special populations.  Gilead's Phase II ELECTRON trial looking at 12 weeks of GS-7977 + RBV posted a SVR4 rate of 88% in genotype 1 patients. Three other arms - including the very-hard-to-treat null responder patients - will be presented later this week. QUANTUM, also a Phase II trial, looking at 12 and 24 week regimens of GS-7977 + RBV in genotype 1, 2 and 3 patients with and without cirrhosis. Data was available only for the 12 week genotype 1 arm, 4 weeks post therapy (SVR4), which garnered a 59% SVR4. It's not clear how many of the 17 patients in the analysis were cirrhotic, but I'm sure that information is forthcoming. It will be interesting to see that breakdown, and if the cirrhotic patient would benefit from 12 additional weeks of GS-7977 + RBV. 

Gilead Sciences, Inc. (GILD)-Bristol-Myers Squibb Company (BMY)'s Experimental Hepatitis C Drug Cured 88% Post-Therapy

4/19/2012 7:22:40 AM

BARCELONA, Spain, Apr 19, 2012 (BUSINESS WIRE) -- Gilead Sciences, Inc. GILD -0.15% today announced interim data from the Phase 2 ELECTRON study examining the investigational once-daily oral agent GS-7977 plus ribavirin (RBV) in treatment-naive patients with genotype 1 chronic hepatitis C virus (HCV) infection. Of the 25 patients who completed 12 weeks of treatment with the GS-7977-based regimen, 88 percent of patients (n=22/25) remained HCV RNA undetectable four weeks after completion of treatment. Three patients experienced viral relapse. These findings are being presented this week during a poster session (Poster #1113) at the 47th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2012) in Barcelona, Spain.

"These preliminary results suggest that 12 weeks of therapy with once-daily oral GS-7977 and ribavirin may be enough to cure hepatitis C in many genotype 1 patients, including those who are currently not candidates to receive interferon," said Professor Edward Gane, MD, Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and principal investigator of the ELECTRON study. "Further investigation of GS-7977 in a variety of patient populations and combinations will be important in assessing the drug's potential as part of an all-oral regimen for hepatitis C."

Results from three additional arms of the ELECTRON study examining GS-7977-based therapy in various patient populations are also being presented this week at the International Liver Congress. These include null responder genotype 1 patients, and genotype 2 and genotype 3 patients, both treatment-naive and prior non-responders.

Overall, GS-7977 was well tolerated and exhibited a favorable safety profile. No patients experienced viral rebound during treatment. No patients discontinued therapy due to an adverse event. The most common adverse events were fatigue, dizziness and headache, and two grade 3/4 laboratory abnormalities were reported.

Gilead today also announced interim results from a second Phase 2 trial (QUANTUM) examining a 12- and 24-week duration of GS-7977 plus RBV in treatment-naive patients. Twenty-five patients were randomized to the 12-week treatment arm: 19 genotype 1 patients; four genotype 3 patients; and two genotype 2 patients. Two genotype 1 patients discontinued therapy prematurely during the 12-week treatment period. At the four-week post-treatment time period, data were available for 17 genotype 1 patients. Of these, 10/17 (59 percent) remained HCV RNA undetectable. Seven patients (41 percent) experienced viral relapse. Additionally, seven of the patients who have reached the eight week post-treatment time period, and who achieved SVR4, remain HCV RNA undetectable.

The overall safety and efficacy profile of GS-7977 was consistent with that seen in ELECTRON. No patients experienced viral rebound while on treatment and no patients discontinued therapy due to an adverse event.

Eleven of the 25 patients (44 percent) in ELECTRON and three of 19 patients (16 percent) in QUANTUM had the IL28B C/C genetic polymorphism. Each of the three patients who relapsed in the ELECTRON study had a different IL28B polymorphism (C/C, C/T or T/T). The seven patients who relapsed in the QUANTUM study either had IL28B C/T (n=4) or IL28B T/T (n=3) genetic polymorphisms. Patients in both studies will continue to be observed to determine sustained virologic response rates at weeks 12 and 24 of follow-up (SVR12 and SVR24).

"The early results from these studies confirm that GS-7977 has the potential to become the cornerstone of an efficacious, all-oral combination regimen for many patients with chronic hepatitis C infection," said John McHutchison, MD, Senior Vice President, Liver Disease Therapeutics, Gilead Sciences. "We look forward to more data unfolding as our trials progress and we expect to initiate additional studies with GS-7977 in combination with other oral antivirals in our pipeline in the coming months. Our goal is to develop a short, simple, safe and effective single tablet regimen for HCV patients throughout the world."

About ELECTRON

ELECTRON is an ongoing Phase 2 randomized open-label clinical study evaluating GS-7977 for the treatment of chronic HCV infection. The primary endpoint of the trial is the safety and tolerability of GS-7977 400 mg once-daily for 8 or 12 weeks, with and without RBV and/or Peg-IFN in HCV patients with genotypes 1, 2 or 3. Study populations include treatment-naive non-cirrhotic patients and those who have failed prior interferon based therapies or "null" responders.

About QUANTUM

QUANTUM is a Phase 2 randomized double-blind placebo-controlled clinical study evaluating GS-7977 for the treatment of chronic HCV infection. The current active arms of the trial are examining GS-7977 400 mg once-daily plus RBV for 12 or 24 weeks in cirrhotic and non-cirrhotic treatment-naive HCV patients with genotypes 1, 2 and 3. The results announced today are for the cohort of patients who have received and completed 12 weeks of therapy with GS-7977 plus RBV (n=25).

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 that the proportion of patients who maintain a sustained virologic response 12 and 24 weeks post-treatment will not be as favorable as the sustained virologic response rates reported in this press release and the possibility of unfavorable results from additional arms of the ELECTRON and QUANTUM studies and subsequent clinical trials involving GS-7977 and RBV. As a result, GS-7977, including in combination with other oral antivirals in Gilead's pipeline, may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of the compounds if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. In addition, Gilead may be unable to develop an all-oral antiviral regimen for HCV genotype 1 patients or a pangenotypic regimen for all HCV patients. 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 Annual Report on Form 10-K for the year ended December 31, 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.

SOURCE: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Susan Hubbard, 650-868-5215 (Investors)
shubbard@gilead.com
Patrick O'Brien, 650-522-1936 (Investors)
pobrien@gilead.com
Cara Miller, 650-576-7849 (Media)
cmiller@gilead.com

Bristol-Myers Squibb and Medivir/J&J expand on Direct Acting Antiviral agreement...

Posted on 4/18/12 on Bloomberg.com - A good day for Medivir/J&J's late stage HCV protease inhibitor TMC435 as both companies inked a deal with BMS looking at mixing and matching Direct Acting Antivirals with TMC435 in interferon-free regimens for treating chronic Hepatitis C. Expect to see more data on both TMC435 and BMS's arsenal of DAA's this week from EASL. 

Bristol-Myers Expands Hepatitis C Accord With J&J, Medivir
By Makiko Kitamura - Apr 18, 2012 5:27 AM PT

Bristol-Myers Squibb Co. (BMY) agreed to conduct two trials of experimental hepatitis C treatments in collaboration with Medivir AB (MVIRB) and Johnson & Johnson. (JNJ) Medivir shares rose as much as 5.7 percent in Stockholm.

The companies will conduct a late-stage trial of Bristol- Myers’ daclatasvir and J&J and Medivir’s TMC435, depending on the outcome of a mid-stage study, Stockholm-based Medivir said today in a statement. A drug interaction study of TMC435 with Bristol-Myers’ BMS-986094 will also be conducted, they said. That expands a collaboration between J&J and Bristol-Myers announced Dec. 2, Medivir said.

The Bristol-Myers drug in the second study entered the company’s pipeline with the acquisition of Inhibitex Inc. for $2.5 billion in February. TMC435 is a protease inhibitor, which blocks the action of the protease enzyme the hepatitis virus needs to replicate, directly stopping it from spreading. BMS-986094 is a nucleotide polymerase inhibitor, which works differently to block the virus’ ability to replicate in the body.

“We see the expanded clinical collaboration as a strong validation of TMC435, especially as we know of no other competing protease inhibitors running interferon-free combination trials with other direct-acting antivirals externally,” which include polymerase inhibitors, said Hans Jeppsson, an analyst at Danske Bank, in a note to investors today.

Medivir shares rose 4.6 percent to 73.25 kronor at 2:17 p.m. in Stockholm, giving the company a market value of 2.29 billion kronor ($339 million).

Drug Combinations
Other nucleotide polymerase inhibitors include Gilead Sciences Inc.’s 7977 compound, which was gained through the company’s acquisition of experimental hepatitis C-treatment maker Pharmasset Inc. for $10.8 billion in November. Bristol- Myers, based in New York, and Medivir are also testing their experimental treatments in combination with Gilead’s 7977.

Drugmakers are exploring cocktails of hepatitis C treatments that exclude interferon, a component of the current standard of care, because of the injectable therapy’s side effects.

Hepatitis C affects as many as 170 million people globally, putting them at risk of developing liver cancer, according to the World Health Organization. The disease is most commonly transmitted through contaminated blood transfusions, organ transplants, contaminated syringes and needle-injected drug use, according to the WHO.

To contact the reporter on this story: Makiko Kitamura in London at mkitamura1@bloomberg.net

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

NPR: The Race To Create The Best Antiviral Drugs

Radio interview and article with noted viral expert Carl Zimmer posted on NPR.org on 4/17/12.  Not specifically related to just HCV, it gives us a broad overview of some of the science behind creating new therapies to treat a variety of viral-related diseases. Very compelling, in my opinion. 

The Race To Create The Best Antiviral Drugs

If you've ever had a bacterial infection like staph or strep throat, your doctor may have prescribed penicillin. But if you've had the flu or a common cold virus, penicillin won't work. That's because antibacterials only kill bacteria, and both the flu and the common cold are viruses. So for illnesses like the flu, doctors prescribe antiviral drugs, which target the mechanisms that viruses use to reproduce.

"For example, there are antivirals for the flu that interfere with the virus as it tries to get out of its host cell," says science writer Carl Zimmer. "So this molecule latches on to that particular protein that the virus uses to escape, and interferes with it so that the virus is trapped inside."

Zimmer's latest piece for Wired magazine profiles the scientists who are developing antiviral medications, and examines the new ways medicine is working to attack viruses.

"There are some really amazing antivirals that have been invented over the last 40 years," he says. "There are antivirals for herpes. There are antivirals for HIV. ... Now, if you were to get Ebola and you tried to take HIV drugs, they'd do you no good at all because that HIV drug only works for HIV. It's a narrow-spectrum drug, and really, there are no broad-spectrum antivirals, at this point."

But scientists are now working to create a "penicillin-like" drug that will target viruses more broadly. In San Francisco, a company called Prosetta is working on a drug that doesn't affect a virus directly. Instead, it works by affecting the proteins that are naturally in cells that help viruses replicate.

"The basic idea behind it is that viruses need help to build themselves," says Zimmer. "What happens is quite amazing: [Viruses] get lots of different proteins in our cells and cooperate to push their own proteins into place. And so the viruses need these groups of host proteins to form."

Prosetta created a drug that prevents the host proteins from performing their cooperative jobs and helping the viruses out. Preliminary studies have shown that targeting these host proteins — and not the virus itself — can stop Ebola, influenza, rabies and other viruses.

Other researchers are working to replace or help interferons, our body's own natural virus-fighting system. Eleanor Fish, a researcher at the University of Toronto, is heading a project to create synthetic interferon, in order to accelerate the body's virus-fighting response.

"Today, people with Hepatitis C can get interferon treatment, but it doesn't work all that well. It has some benefit, but not as much as Eleanor Fish would like," says Zimmer. "So she has been essentially tweaking the interferon molecule to make it more effective, to make it last longer, to make it safe and to make it cheap. Because what she wants to do is deploy interferon all over the world where there isn't fancy refrigeration. She wants to help people who are dealing with viruses in very remote places."

A third approach, says Zimmer, involves creating an artificial protein that would latch onto viruses and then instruct them to literally self-destruct. Spearheaded by Todd Rider at MIT, the project has been tested in cells and in mice.

"Rider's basically hot-wiring your cells so that as soon as they get infected by a virus, that trips a switch," says Zimmer. "This doesn't exist naturally, but if you were to take a pill, the thinking is, then this molecule would go into your infected cells, and as soon as it detected the virus, it would kill the infected cell, and you would recover from your disease."

But successfully eradicating viruses may bring a host of other problems, says Zimmer. He points to broad-spectrum antibiotics, which wipe out good bacteria in addition to bad bacteria.

"Eventually your body may recover, and it can take awhile, and there may be some bad consequences of the antibiotics themselves," he says. "So it's going to be interesting to see what happens in the future if we are, in fact, knocking out lots of viruses. Because we don't understand the full ecology of the viruses that get into our bodies."

There are trillions of viruses that live in our bodies, even when we're not sick, says Zimmer.

"Some are harmful, some may not be harmful," he says. "Some may even help us defend against other viruses. It's very complicated in there, and we don't really understand it very well yet."

hysicians are now using bacteria to combat other diseases. Zimmer points to an example of a patient infected with the Clostridium difficile bacteria, which causes severe diarrhea and can frequently return, even when treated with antibiotics. The patient was treated with a transfusion of gut microbials from a healthy individual's fecal material to restore the bacterial flora in her intestinal tract.

"Literally two days later she started feeling better, and a couple weeks later, when they went to sample the bacteria that was there, they couldn't find the C. difficile anymore. It was just gone," he says. "The only thing they had done was essentially restore her ecology, essentially like restoring a wetland."

Zimmer says fecal transplants have only been performed on patients when all other options fail — but they are seemingly quite effective.

"The problem is, as some other journalists have reported, is that the FDA has a very difficult time figuring out how to come up with regulations for this," he says. "Before it's going to become a widespread practice, the FDA is going to have to move beyond its old paradigm of giving people regular drugs to being able to give people tailored concoctions of living things — of bacteria, of maybe even viruses — as medical treatments."

These bacteria and viruses work in conjunction with other bacteria and viruses in the body, but scientists still know very little about their mechanisms, says Zimmer.

"There's this whole ecosystem of interactions going on inside our own bodies that we do not understand — barely at all," he says. "Scientists are just starting to figure it out with very big projects where they're sequencing all the genes these microbes have. But they're just at the beginning of understanding it."

The emerging role of the Infectious Disease physician in treating HCV...

An article published in POZ magazine on 4/13/12 on an opinion piece e-published ahead of print in   'Clinical Infectious Diseases' authored by Barbara McGovern, MD of Tufts University School of Medicine.  She makes a plea for Infectious Disease doctors to start treating Hepatitis C and relieve some of the burden on the thin and overworked ranks of Hepatologists.  She suggests 'establishing "centers of excellence" and instituting joint fellowships wherein HCV experts can pass their knowledge along to ID physicians; presenting conferences and workshops devoted to HCV evaluation and management; collecting data from the membership of the Infectious Diseases Society of America (IDSA) on obstacles to hepatitis C patient care; and offering real-time updates to HCV treatment guidelines.'  It's my opinion that IDs offer the perfect discipline for treating HCV and HCV/HIV co-infection as newer, all-oral, interferon-free regimens greatly expand the the pool of patients elgible (and willing) to be treated.  IDs have treated HIV for years - a disease state whose early treatment years display some uncanny parallels to the genesis of Direct Acting Antiviral therapy for Hepatitis C. The IDs know virology, they understand the implications for viral resistance, the concept of 'drug cocktails' which attack the virus at different points along it's life cycle, they know about side effect management, and most of all, their economic model is strikingly similar to that of the in-the-trenches Hepatologist.  It seems like a good fit from out here looking in. 

April 13, 2012

More Infectious Disease Docs Treat Hep C

We may soon see an end to obstacles in the care of people living with chronic hepatitis C virus (HCV)—but only if infectious disease (ID) doctors work with and learn from hepatologists, according to an opinion piece authored by Barbara McGovern, MD, of Tufts University School of Medicine and published online ahead of print by Clinical Infectious Diseases.

ID specialists have historically been reluctant to treat hepatitis C, even among their own patients living with HIV, because of the complexities of prognostic testing and combination treatment, low cure rates among people with genotype 1 HCV and the need for expert management of side effects.

HCV coinfection is more amenable to treatment now than in the past—including for those coinfected with both HIV and HCV—with the current generation of direct antiviral agents providing a 75 to 85 percent cure rate.

Further improvements—such as all-oral regimens that don't involve interferon—are expected within the next few years and will likely benefit both HCV-monoinfected and HIV/HCV-coinfected patients. This would be a great boon for all people living with HCV, for whom treatment can lead to remission of liver disease and reduced risk of liver cancer and cirrhosis.

With an estimated 170 million HCV cases worldwide—including 5 million in the United States, where hepatitis C death rates now exceed those from HIV—hepatologists, the usual go-to medical experts for hepatitis C care and management, are overwhelmed by the number of patients seeking their services. Their efforts will be stretched even thinner if the Centers for Disease Control and Prevention (CDC) implements planned screening guidelines that recommend testing everyone born between 1945 and 1965—an age range with an especially high HCV prevalence.

Bringing more people into care for hepatitis C, McGovern argues, will require expanding the ranks of ID specialists capable of dealing with the virus and its complications.

One reason HCV care has required highly specialized attention from hepatologists was the need for a liver biopsy to measure the progress of the disease. This may no longer be necessary, thanks to noninvasive testing via such methods as blood tests and elastography (measurement of tissue stiffness via ultrasound or magnetic resonance), which can be performed by ID specialists.

Another main reason why hepatologists have been needed for HCV therapy is the risk of decompensated cirrhosis—when a cirrhotic liver begins to lose its ability to function—for patients who don't receive antiviral therapy or whose therapy fails. Managing the complications of decompensated cirrhosis requires a hepatologist's specialized training. However, early HCV treatment greatly decreases the risks of cirrhosis.

Lastly, modern combo therapies for HCV require extensive knowledge of the relevant antiviral drugs and their interactions.

McGovern recommends sidestepping this dearth of hepatologists by cross-training ID specialists in the intricacies of HCV infection. Her recommendations include establishing "centers of excellence" and instituting joint fellowships wherein HCV experts can pass their knowledge along to ID physicians; presenting conferences and workshops devoted to HCV evaluation and management; collecting data from the membership of the Infectious Diseases Society of America (IDSA) on obstacles to hepatitis C patient care; and offering real-time updates to HCV treatment guidelines.

"Although HCV does not command the same media attention as for some emerging infectious diseases," McGovern wrote, "advancing liver disease will be exacting a tremendous toll in morbidity and mortality in the decades to come if wider access to treatment is not realized in the near future. In fact, in 2007, deaths from HCV infection exceeded deaths from HIV in the United States. Millions of HCV-infected patients will be depending on an expeditious response from the ID community, as we have done for many other infections in the past."

Seeking Alpha - Achillion Will Soar Higher On New Hepatitis C Drug In 2013

Posted on 4/16/2012 on Seeking Alpha.com. I'm trying to figure this guy out. He makes some valid points on Achillion's PI ACH-1625, but says nothing about their NS5A inhibitors. Then he mentions GSK's Promacta (Eltrombobag) as a 'competitor' and a 'Hepatitis C drug', which doesn't do much for this particular person's street cred. Anyway, I like to root for Achillion and I like it when people say nice things about the company, so I'm including it here for your reading pleasure. 

Achillion Will Soar Higher On New Hepatitis C Drug In 2013

By Vatalyst - Seeking Alpha.com

April 12, 2012

Achillion Pharmaceuticals (ACHN) has risen 51% since last year, which is a surprising number for a development stage pharmaceutical industry with no FDA approved drugs on the market. The news has been hyping up Achillion's hepatitis C drug ACH-1625, which is only just now ending Phase 2 clinical trials. Along with ACH-1625, are four other hepatitis C drugs and one bacterial infection antibiotic, ACH-702. The hepatitis C drug pipeline is composed of some very unique drugs and mechanisms for treating hepatitis C.

Should these drugs gain FDA approval, there would be a major upside for the company to sell ACH-1625 state side and worldwide to nearly corner the market. However, ACH-1625 is only just finishing Phase 2 and releasing results. I always highly advise against investing in any company with promising drugs that have not been FDA approved.

The first reason is that Achillion is getting great news hype about ACH-1625, which is causing the stock price to increase very well. But, Achillion is now starting Phase 3 clinical trials and will not have any more news reports that would cause a stock rise in the next year. The second reason is that more often than not, drugs fail to gain FDA approval for hundreds of different reasons, including toxicity, efficacy, and potency. It is never safe to bet on a drug before it is FDA approved so do not invest until there are conclusive and positive phase 3 trial results released.

Finally, due to the fact that ACH-1625 is starting phase 3 trials in the beginning of 2012, we cannot expect to see the drug on the market until at least late 2013 or early 2014.

Phase 3 trials can take a year or longer, plus new drug application for the FDA takes a substantial amount of time. Therefore, I do not expect stock price to do much of anything until late 2013 at the earliest. If you are a long-term investor and already own stock with Achillion, sit tight until late 2013 when share price will see a major upside if the clinical results are positive. If you are short term, keep a close eye on the company until late 2013 and if the phase 3 results are positive then it is time to invest.

Achillion has a market cap of $773 million and a 52 week range of $4-$13. Achillion has a competitor in the hepatitis C drug Promacta by GlaxoSmithKline (GSK), which has a market capitalization of $223 billion, a 52-week range of $39-$47 and a price to earnings ratio of 27.45. Achillion's next competitor is a hepatitis C drug, TMC435, by Johnson & Johnson (JNJ) with a 52 week range of $59-$68, a price to earnings ratio of 18.74 and a market cap of $179 billion. The last competitor of Achillion are three hepatitis C drugs by Roche Holding AG (RHHBY.PK) with a price to earnings ratio of 14.3, a market cap of $145 billion and a 52-week range of $42-$43. For a company that has no FDA approved products on the market, Achillion seems to be in pretty good standing with its competitors.

Johnson & Johnson is set to be Achillion's biggest competitor. It currently has a hepatitis C drug, TMC435, entering Phase 3 trials. The results of the Phase 2 trials showed that the drug was effective, safe, and 83% of patients were able to discontinue treatment with TMC435 after 24 weeks. With the release of this positive clinical trial news, Johnson & Johnson is receiving equal amounts of positive hype over this hepatitis C drug as Achillion. It is possibly receiving even more hype when considering the other drugs currently in Phase 3 of the Johnson & Johnson pipeline. Share has stayed relatively the same over the past year with a nearly 10% increase. I feel that right now Achillion and Johnson & Johnson are going to mirror one another until the Phase 3 data is released. I recommend keeping an eye on both companies until then; once the data is released we will know which company has the better drug and which is worth investing in.

Roche Holding AG is currently developing three hepatitis C drugs in its pipeline. These drugs are all in Phase 2 testing and will not be ready for the market until late 2014 at the very earliest, most likely by 2016. This is assuming that the drugs even pass FDA regulation in the coming years. I see no real competition from Roche Holding AG in the next few years to hurt share price of Achillion, but Roche Holding AG would be a good company to keep an eye on and possibly invest in if ACH-1625 ends up failing FDA approval.

GlaxoSmithKline has developed an FDA approved drug, Promacta, used for the treatment of hepatitis C in compound with other treatments. I feel that this drug wont provide much competition for ACH-1625 should it become FDA approved. Promacta's main function is to increase blood platelet count in patients with hepatitis C while other drugs attack the hepatitis virus, whereas ACH-1625 directly treats hepatitis C with no need for compounding with other drugs. I feel that ACH-1625 would out-compete Promacta relatively easily and no reason to be wary of GlaxoSmithKline.

To sum up Achillion's stance on the market, it is too soon to be investing in ACH-1625. There is no current upside to raise share price substantially for at least the next year while the trials carry on. Considering Johnson & Johnson's position currently mirrors that of Achillion, it would be smart to let the research data of both company's respective drugs decide which is going to be the best bet in 2013. Lastly, I believe ACH-1625 will beat out GlaxoSmithKline's Promacta if it becomes FDA approved, so expect little competition on the market from GlaxoSmithKline.

Bloomberg BusinessWeek on Gilead's GS-7977 and critical upcoming data from EASL...

Article posted 4/12/12 on Bloomberg BusinessWeek - All investor eyes on Gilead regarding their EASL data for GS-7977 both in combo with RBV in treatment-naive patients and in combo with BMS's daclatasvir +/- ribavirin. No pressure, though. *cough*


Gilead Bets on Hepatitis C Data to Back Pharmasset Deal

Gilead Sciences Inc. (GILD) (GILD), after paying $10.8 billion for the developer of an experimental hepatitis C drug, will soon give investors a better sense of whether its largest-deal ever is going to pay off.

Beginning next week, Gilead will release data from dozens of patients who have tried the medicine, providing the most complete evidence yet about its prospects for treating 170 million people who are infected with the virus globally. Trial results reported in 10 people in February spurred wild swings in the company’s stock price.

Gilead, the world’s largest maker of HIV drugs, has fallen 10 percent in the past four years, and is facing the loss of half of its revenue from patent expirations on AIDS medicines beginning in 2018. Despite that, 26 analysts (GILD) advise buying the shares, and seven suggest holding them.

“They will be there as one of the key players to treat a very large unmet medical need in hepatitis C, and one of the first players,” said Joshua Schimmer, a Leerink Swann & Co. analyst. “You can make a very strong case that Gilead shares are worth owning through the volatility.”

The purchase of Pharmasset Inc., announced Nov. 21, was designed to add a heavyweight product to diversify Gilead in an area -- infectious disease -- where the Foster City, California- based biotechnology company has expertise and an established sale force.

The company became a leader in AIDS treatments by finding the right combinations of drugs to help change the disease from a quick killer into one that’s manageable. Researchers say hepatitis C also may be attacked with drug cocktails. It’s a matter of finding “the right recipe,” said Mani Subramanian, a Gilead vice president of clinical research.

Liver Meeting
Investors are looking to results to be reported beginning at next week’s European Association for the Study of Liver meeting in Barcelona to define what role Gilead’s hepatitis C drug, known as 7977, will play in a developing market for new medicines that is expected to reach $20 billion.

In data reported on Feb. 2, four weeks of Gilead’s medicine seemed to eradicate the virus in 10 patients who hadn’t responded to prior rounds of therapy, boosting the company’s stock market value (GILD). On Feb. 17, when some patients relapsed, Gilead shares fell the most in 11 years.

“You have to be kind of astounded by it,” Leerink Swann’s Schimmer said in a telephone interview.

One key study weighs the performance of Gilead’s 7977 in tandem with an experimental product from Bristol-Myers Squibb Co. (BMY) (BMY) when used by all types of patients. Others will report on 7977’s effectiveness in those who have never been treated.

Bristol-Myers Compound
Bristol-Myers’s compound, BMS-790052, hinders a protein called NS5A that creates a scaffolding around the virus, securing it so it can replicate, Gilead’s Subramanian said. His company’s drug integrates itself into the virus’s replicating process, preventing it from churning out copies.

The new hepatitis C drugs also promise to work more quickly and be safer than the current standard of care that combines an antiviral called ribavirin with interferon, an injectable immune-boosting protein, studies have shown.

“We’re very excited about this Bristol-Myers study,” Subramanian said in an interview at the company’s headquarters. “We’ll know whether you even need ribavirin if you have a NS5A in the mix.”

Proving the worth of Bristol-Myers’s product in combination with 7977 could also help Gilead down the line when GS-5885, its own NS5A inhibitor, is put before the U.S. Food and Drug Administration for approval. The product is now in the second of three phases of trials generally required for clearance.

Ribavirin Combination
Gilead is expected to report at the Barcelona conference how 7977 works in combination with ribavirin after 12 weeks of therapy in those who haven’t had other treatments before, so- called naïve patients. This will help establish which patients can be cured, or not, without interferon.

If Gilead’s hepatitis C drug is approved, at the end of 2013 at the earliest, it may add $3 billion to $4 billion in revenue by 2018, said Michael Yee, an analyst with RBC Capital Markets in San Francisco. That would help replace sales from Atripla, the most widely used HIV medicine, and Truvada, a component of Atripla, he said. The medicines generated $6.1 billion in 2011 sales, or 73 percent of Gilead’s revenue.

“The company did have very steady revenue and earnings growth, but they’re looking to accelerate that,” Yee said. “The growth potential of the company has significantly changed, with higher risk and higher reward.”

No Death Knell
The finding last month that some patients have relapsed shouldn’t be looked at as a death knell for the developing product, Gilead’s Subramanian said.

The data “means one of two things,” he said in an interview. “Do you need longer duration, or more drugs?”

Geoff Porges, an analyst with Sanford C. Bernstein & Co. in New York with a market perform rating on Gilead, isn’t so sure.

The failure of 7977 to cure people who had previously been treated “shocked the world,” and means Gilead won’t dominate the field as some had expected, he wrote in a note to clients. “It changes the treatment landscape,” he wrote, and “highlights the vulnerability of Gilead’s stock to any stumbles.”

Subramanian remains philosophical about the hepatitis c therapies: “It’s like cooking,” he said. “At some point we’ll figure out the right recipe.”

To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

Chronic HCV associated with high comorbidities in US population...

A synopsis of a journal article by Louie et al, appearing in 'BMC Infectious Disease' (see citation below) posted on the Infection Control Today website on 4/11/12. The study, called "The High Comorbidity Burden of Hepatitis C Virus Infected Population in the United States", is a retrospective cohort study using a US medical claims database designed to estimate the 2 year prevalence of comorbidities with chronic HCV.  The result? A LOT of cormorbidities are associated with chronic HCV, and the authors call for increased access to treatment to reduce the burden of HCV.

High Comorbidity Burden of the U.S. Hepatitis C Virus-Infected Population

Chronic hepatitis C (HCV) disease can be complicated with comorbid conditions that may impact treatment eligibility and outcomes. The aim of the study by Louie, et al. (2012) was to systematically review comorbidities and symptoms in an HCV-infected population, specifically assessing comorbidities associated with HCV antiviral treatment and disease, as well as comparing comorbidities between an HCV-infected and uninfected control population.

 

This was a retrospective cohort study within a United States medical claims database among patients with chronic HCV designed to estimate the two-year period prevalence of comorbidities. Patients with two HCV diagnosis codes, 24 months of continuous health insurance coverage, and full medical and pharmacy benefits were included.

Among a chronic HCV cohort of 7,411 patients, at least one comorbid condition was seen in almost all patients (>99%) during the study period. HCV-infected patients reported almost double the number of comorbidities compared to uninfected controls. Of the 25 most common comorbidities, the majority of the comorbidities (n = 22) were known to be associated with either HCV antiviral treatment or disease. The five most frequent comorbidities were liver disease [other] (37.5%), connective tissue disease (37.5%), abdominal pain (36.1%), upper respiratory infections (35.6%), and lower respiratory disease (33.7%). Three notable comorbidities not known to be associated with antiviral treatment or disease were benign neoplasms (24.3%), genitourinary symptoms & ill-defined conditions (14.8%), and viral infections (13.8%).

The researchers concluded that this U.S. medically insured HCV population is highly comorbid. Effective strategies to manage these comorbidities are necessary to allow wider access to HCV treatment and reduce the future burden of HCV disease and its manifestations. Their research was published in BMC Infectious Diseases.

Reference: Louie KS, et al. The high comorbidity burden of the hepatitis C virus infected population in the United States. BMC Infectious Diseases 2012, 12:86 doi:10.1186/1471-2334-12-86

Merck and Codex go "green" with new production process for Victrelis...

Article posted 4/10/12 on InPharm.com - Pressures on price continue to increase and with large patent expirations on the horizon, what's a Big Pharma company to do to maintain shareholder-friendly profitability levels?? One answer is to create better efficientcies in the drug production process, thereby dropping the price and (hopefully) creating bigger margins. And if you can do it 'green', well, that's some corporate goodwill for you.   Merck has teamed up with catalyst Codexis to develop a more efficient production process for Merck's HCV protease inhibitor, Victrelis. Codexis fits into a very interesting niche that will certainly maintain appeal to drug manufacturers as the pressure to drop prices increases. Definitely a niche I'm going to make an effort to watch in the coming years. 

Codexis and Merck develop green Victrelis production

Published on 10/04/12 at 12:23pm

Merck has teamed up with catalyst specialist Codexis to develop a more efficient manufacturing process for recently-approved hepatitis C treatment Victrelis.

Merck was granted approval for NS3/4A protease inhibitor Victrelis (boceprevir) in the US last May and in Europe the following July.

Sales of the product have quickly ramped up to reach nearly $90 million in the fourth quarter of 2011 and $140 million for the full year, despite being available only in a handful of markets.

Analysts have tipped Victrelis as a future blockbuster, and Merck has enlisted the aid of Codexis to make the production process more efficient and boost its profit margin for the drug at a time when the firm is facing patent expiries on some key product lines.

Merck and Codexis scientists developed an enzyme-based production method for a key intermediate in the production of boceprevir that has been recently published in the Journal of the American Chemical Society (JACS).

The JACS publication describes the creation and characterisation of a biocatalyst that was capable of performing a key step in the synthesis of boceprevir.

The new method increased chemical intermediate yield 150% over the previous process, according to the paper. Moreover, it reduced raw material use by 60%, water use by 61% and overall process waste by 63%, making the manufacturing process greener.

"Incorporation of innovative environmentally sustainable means of manufacture is a key aspect of our research and development strategy," commented Richard Tillyer, senior vice president for Discovery and Preclinical Sciences at Merck Research Laboratories.

"Enzymatic based methods can offer a biodegradable and renewable alternative to currently employed methods."

Biocatalysts - generally based on enzymes - have been used on a small scale in the pharmaceutical industry for many years, but it is only in the last few years that they have migrated into the commercial-scale manufacturing environment.

Pressures on the profitability of drugmakers have encouraged the industry to cut costs and boost efficiencies across the board, including in manufacturing, and Codexis has tapped into that trend.

Last year the company reported sales growth of 16% to $124 million that it said was "driven by increased sales to both generic and innovator pharmaceutical customers".

Phil Taylor

BMS-Gilead EASL data leak spurs speculation...

Posted 4/9/12 on The Street. From the sounds of it, embargoed data showing the EOT response with daclatasivr and GS-7977 combo was mistakenly published on the EASL website over the weekend, showing an encouraging 97% EOT response in tx-naive genotype 1 patients and 90% in genotype 2 and 3 subjects. An analyst picked this up and sent a research report to his clients. It's unclear at this time whether this was the arm with ribavirin or without... further speculation on my part says that if it is indeed without ribavirin, we need to keep a close eye on the relapse rates. EOT is, unfortunately, not SVR. 

Bristol-Gilead Hep C Drug Data Leaks
Adam Feuerstein

04/09/12 - 09:29 AM EDT

Updated with a corrected research report from Jefferies, noting that the end-of-treatment response to daclatasvir and GS-7977 was actually 97%, not 93%.

BOSTON (TheStreet) -- An early peek at data from a closely watched mid-stage study combining hepatitis C drugs from Bristol-Myers Squibb(BMY) and Gilead Sciences(GILD) has leaked in advance of the European Association for the Study of the Liver (EASL) annual meeting.

Ninety-seven percent of genotype 1 hepatitis C patients treated with Bristol's daclatasvir and Gilead's GS-7977 has undetectable viral levels after 12 weeks of treatment. For genotype 2/3 patients, the 12-week response rate was 90%, according to a research note published Monday by Jefferies analyst Thomas Wei.

Wei called the end-of-treatment response to daclatasvir-GS-7977 "encouraging" and "positive."

These data from Bristol and Gilead were supposedly embargoed by EASL and were therefore not made available to the public when research abstracts for the EASL meeting were posted online on April 4.

In an email to clients Monday, Jefferies said the Bristol-Gilead abstract was "briefly posted" on EASL's web site over the weekend before being taken down.

Officials with EASL have not responded to questions regarding the leak of the research abstract.

Interim results from a phase II study combining Bristol's NS5a inhibitor daclatasvir (BMS-52) with Gilead's GS-7977 in genotypes 1, 2, and 3 is the most highly anticipated data presentation at the EASL meeting this year. The study is important because it will be one of the first glimpses at the Hep C-killing potency of these two classes of direct-acting antivirals combined into a single, all-oral therapy.

Early cure rates from the dacalatasvir-GS-7977 study -- defined as the percent of patients with undetectable viral loads four weeks after cessation of treatment -- will be presented at the EASL meeting, which takes place April 18-22.

--Written by Adam Feuerstein in Boston.

The Street - "Winners, Losers From EASL Hep C Data Dump"

Article posted on 4-4-12 on The Street.com. The author is right - the data people really want to see (tx-naive arm of ELECTRON; QUANTUM and GS-7977 + daclatasvir) won't be available until 4-21 after the Late Breaker sessions. After all, EASL has to fill seats for five days and Barcelona isn't just up the street for most of us. These leaves room for speculation - LOTS of speculation in the case of Idenix, which saw it's market cap take a hit after an analyst speculated that because nuc mericitabine (RG7128) under-performed in the JUMP-C study, it's distant cousin IDX184 would likely do the same.  The Idenix CEO quickly retorted that such comparisons are unfounded. We'll see - amazing the power of the Wall Street analyst in this market place. 

Adam Feuerstein
04/04/12 - 03:20 PM EDT
Updated with new information, including comments from the CEO of Idenix Pharmaceuticals.

BOSTON (TheStreet) -- The European Association for the Study of the Liver (EASL) finally released hepatitis C drug research abstracts Wednesday ahead of its closely followed conference in two weeks. But investors looking for clear winners and losers in the race to develop new all-oral hepatitis therapies came away disappointed.

As with all things hepatitis C, the EASL abstract "data dump" raised more questions than provided answers, in part because a lot of the data investors most wanted to see remains under wraps.

Still, Wall Street loves to make snap judgments, so Abbott(ABT) shares rose less than 1% to $61.60 on strong results from a small mid-stage study of a three-drug, all-oral regimen, which resulted in hepatitis C cure rates greater than 90%.

Abbott's gain was Gilead Science's(GILD) pain, causing the latter's shares to fall 2% to $47.13. Further hurting Gilead Wednesday was the absence of new data on GS-7977, the hepatitis C drug acquired in the $11 billion Pharmasset purchase. EASL chose not to make GS-7977 data available Tuesday, withholding for presentation at the meeting itself.

EASL also kept under wraps data from an important study combining Bristol-Myers Squibb's(BMY) daclatasvir with Gilead's GS-7977. A Bristol spokesperson did confirm, however, that interim results tracking early cure rates from this study will be presented at the EASL meeting.

The biggest loser Wednesday appears to be Idenix Pharmaceuticals(IDIX), with shares down 12% to $8.99 but not because of any new information released on its hepatitis C drugs. Instead, investors appear to be worried about the future of Idenix's lead drug IDX184 based on poor results released today on a similar drug being developed by Roche.

EASL's International Liver Congress is being held April 18-22.

More details on the hepatitis C research abstracts made public Wednesday:

Abbott: Today's results come from a phase II study of its own all-oral Hep C regimen consisting of protease inhibitor ABT-450, a ritonavir booster and the non-nuke polymerase inhibitor ABT-333. The study enrolled treatment naive genotype 1 patients as well as treatment-experienced non-responders. Patients were treated for 12 weeks.

In the treatment-naive patients, SVR12 or hepatitis C "cure" rates were 93% and 95% for the low- and high-dose arms, respectively. These are some of the strongest cure rates seen for new hepatitis C therapies, particularly for regimens that exclude injectable interferon. The high cure rates are even more impressive given that a majority of the patients enrolled were diagnosed with the more difficult-to-treat genotype 1A subtype.

In patients who failed to respond to previous treatment, the Abbott all-oral regimen resulted in a cure rate of 47%.

One looming concern about the Abbott hepatitis C regimen is convenience. As formulated now, patients must take one pill once per day and another two pills twice per day. For a relatively short treatment duration of 12 weeks, remembering to take a total of five pills per day may not be a problem, unless competing companies develop equally effective and simpler therapies.

Idenix: A Roche study combining the nucleoside polymerase inhibitor mericitabine, a protease inhibitor danoprevir and ribavirin proved to be relatively unsuccessful, with a cure rate of 41% overall (71% in genotype 1b patients and just 26% in the harder-to-treat genotype 1a patients.)

This study has nothing to with Idenix except that the company's own nucleoside polymerase inhibitor IDX184 is perceived by some investors to be similar to that of Roche's mericitabine. This raises concerns that any future combination regimen pairing IDX184 with a protease inhibitor may result in similarly poor cure rates.

Idenix CEO Ron Renaud calls comparisons between IDX184 and mericitabine "ridiculous," adding that data already presented shows '184 to be more like GS-7977 than mericitabine. "Comparing '184 to mericitabine, I don't know where that comes from," says Renaud. "It's just conjecture and assumptions being made by some… All we can do is continue to generate good data. We remain as optimistic about '184 as we've ever been." Hepatitis C data not yet released by EASL but expected at the meeting:

Gilead Sciences: Data from two separate but similar studies (ELECTRON and QUANTUM), both involving the two-drug combination of GS-7977 plus ribavirin in treatment-naive genotype 1 patients.

Gilead has said results from the QUANTUM study could be announced in a press release early in the second quarter i.e. before the start of the EASL meeting. Investors are sure to scour the EASL web site Thursday for any early patient data that may give a hint about the later '7977 results. Much is riding on the outcomes from these treatment-naive patient studies because '7977's potency was cast in doubt due to poor results in so-called "null responder" patients.

Bristol-Myers Squibb: Interim results from a phase II study combining Bristol's NS5a inhibitor daclatasvir (BMS-52) with Gilead's GS-7977 in genotypes 1, 2, and 3 is the most highly anticipated data presentation at the EASL meeting this year. The study is important because it will be one of the first glimpses at the Hep C-killing potency of these two classes of direct-acting antivirals combined into a single, all-oral therapy.

If this study is successful, Bristol is expected to swap out GS-7977 for its newly acquired nuke INX-189, gained from the Inhibitex acquisition. Gilead may also capitalize on the study by combining GS-7977 with its own NS5a inhibitor.

--Written by Adam Feuerstein in Boston.