Forbes.com: Why A Change In A Bristol-Myers Hepatitis C Trial Has Big Implications

Posted 6/29/12 on Forbes.com . Commentary on the implications of BMS restricting enrollment in COMMAND-3 to subjects with genotype 1b, which makes up only 25% of the genotype 1 patients here in the US. Also see http://www.viralmatters.blogspot.com/2012/06/presidio-pharmaceuticals-completes.html on a tx-naive patient having baseline resistance to PPI-668, Presidio's NS5A inhibitor.

Why A Change In A Bristol-Myers Hepatitis C Trial Has Big Implications

Is a promising new class of drugs for treating hepatitis C going to be limited because patients with the most common genotype of the virus are likely to develop resistance to the medications? This is the possibility raised by a Wall Street analyst after learning that Bristol-Myers Squibb has altered the protocol for a clinical trial for its daclatasvir antiviral, which is believed to be the most potent in the forthcoming NS5a class of hepatitis c treatments.

According to ClinicalTrials.gov, the drugmaker changed the protocol to its COMMAND-3 trial, which compares its drug in combination with interferon and ribavirin to Incivek, a protease inhibitor sold by Vertex Pharmaceuticals, along with interferon and ribavarin. What was the change? Bristol-Myers restricted future enrollment to patients who have only genotype 1b HCV, rather than all genotype 1 patients (see this and this).

“This effectively eliminates from the trial the most common HCV genotype in the US – 75 percent of HCV is genotype 1 in the US, 80 percent of genotype 1 is genotype 1a,” Sanford Bernstein analyst Tim Anderson wrote in a recent investor note. “This change, some three months after the study started enrollment, suggests that some form of virologic failure has emerged in the patients with these genotypes… The NS5a class, as a whole, might be limited by the propensity to rapidly develop virological resistance, and by significant differences in potency from one viral genotype to another.”

He adds that the change in the protocol has “major strategic and tactical implications” for the hot and fast-growing hepatitis C market. How so? Several drugmakers are developing NS5a treatments and the possibility that these drugs generate resistance to the virus may prompt changes in how different types of medications are combined and, consequently, alter various corporate strategies for drug development, alliances and dealmaking.

Take Gilead Sciences. The drugmaker is developing an NS5a, which has the code name of GS5885, as well as another that is a nucleotide inhibitor, or nuke, which Gilead calls GS7977 and believes could be the cornerstone of the first all-oral regimen for hepatitis C. Gilead, you may recall, acquired GS7977 last fall as part of its $11 billion acquisition of Pharmasset, a bet that has transformed the investor view of the drugmaker (back story).

Two months ago, results of a study that combined daclatasvir with GS7977 suppressed hepatitis C in most patients four weeks after completing treatment, raising hopes about the prospects for a therapy that does not involve an injectable medication. But further collaboration between the two drugmakers appeared uncertain, because Gilead indicated a preference for developing its own NS5a drug with GS7977 (look here).

However, as Anderson notes, the Gilead NS5a drug is less potent than daclatasvir, which “increases the risk for Gilead of sticking with GS5885. On the Bristol side, their ‘go-it-alone’ strategy may be developing a hole, increasing the urgency of incorporating daclatasvir into an all-oral combination with a potent resistance-fighting nuke such as GS7977. This collaboration appears to have become more important to both parties,” he writes.

Both drugmakers declined comment on this topic, although late last month, Bristol-Myers ceo Lamberto Andreotti renewed a call for Gilead to jointly develop their hepatitis C medications. And Bristol-Myers has not responded to questions about the change in the trial protocol.

Looking ahead, Anderson sees greater potential for combination therapy that relies on three drugs, instead of two, including GS7977 from Gilead, since the response to NS5a drugs suggests there can be limitations to at least one of the agents that drug developers would want to use in a one-two punch. And he believes Gilead’s prospects for creating one “super-regimen” for all subtypes with GS7977 and GS5885 alone, or even with ribavirin, have fallen.

As for other drugmakers, the questions concerning the NS5a drugs may result in slightly extended utility for Incivek as well as Victrelis, another protease inhibitor that is sold by Merck. This also suggests additional jockeying surrounding the NS5a drugs being developed by Achillion Pharmaceuticals and Idenix Pharmaceuticals, since larger drugmakers may decide to adjust their strategies and portfolios in response to the changing dynamics of this class of treatments.

Presidio Pharmaceuticals completes Phase 1b proof-of-concept trial with HCV NS5A inhibitor PPI-668...

Posted 6/26/12 on Market Watch.com.  San Francisco's Presidio Pharmaceuticals successfully completed it's Phase 1 Proof-of-Concept trial for it's (perhaps pan-genotypic) HCV NS5A inhibitor, PPI-668. The data was convincing enough for the company to slot PPI-668 for Phase II trials, although in what combination remains a mystery. One patient in the highest dose group (240mg) was found to be fully resistant to PPI-668 at baseline - a little worrisome given that these were treatment-naive genotype 1 subjects. This may or may not provide insight into why BMS narrowed enrollment to it's COMMAND-3 trial with daclatasvir to genotype 1b subjects. 


SAN FRANCISCO, Jun 26, 2012 (BUSINESS WIRE) -- Presidio Pharmaceuticals, Inc. announced today successful completion of Phase 1b clinical testing of its lead HCV NS5A inhibitor in patients with HCV genotype-1 infection, with positive efficacy and safety observations supporting advancement of PPI-668 to Phase 2 combination studies.

The randomized, blinded Phase 1b trial of PPI-668 involved sequential cohorts of treatment-naive HCV genotype-1 patients who received oral doses of PPI-668 of 40, 80, 160 or 240 mg, once daily for three consecutive days. Within each 10-patient cohort, patients were randomized 8:2 to PPI-668 or placebo.

In all of the Phase 1b dose cohorts, PPI-668 was well tolerated with no serious or severe adverse events, no premature treatment discontinuations and no apparent pattern of treatment-related clinical side effects or laboratory abnormalities.

The Phase 1 clinical results indicate that PPI-668 had a favorable pharmacokinetic (PK) profile that included rapid achievement of high (micromolar) plasma levels, prolonged maintenance of potentially effective levels between doses, and achievement of steady-state pharmacokinetics after the first dose.

The Phase 1b efficacy observations indicated consistently rapid, marked reductions in patients' serum viral load (HCV RNA levels), that were dose-related. Patients' HCV RNA reductions typically exceeded 3 log10 IU/ml (99.9%) by Day 2. During the 3-day treatment period, mean maximal HCV RNA reductions for the 4 dosing groups were:

-- 3.2 log10 IU/mL in the 40 mg dose group

-- 3.5 log10 IU/mL in the 80 mg dose group

-- 3.5 log10 IU/mL in the 160 mg dose group

-- 3.7 log10 IU/mL in the 240 mg dose group

There was only one minimal-responder in the trial. A patient in the 240 mg dose group was found to be fully resistant at baseline with 100% of this patient's pre-treatment HCV RNA containing 3 genetically linked NS5A resistance mutations. This patient was excluded from the efficacy analysis of the 240 mg cohort, since he was pre-resistant and could not contribute to dose-response inferences.

Five other patients with detectable resistance mutations at baseline, including those harboring the relatively common L31M variant, responded well to PPI-668 treatment, with multi-log HCV RNA reductions.

A protocol amendment has been completed to explore the pan-genotypic clinical efficacy of PPI-668 in HCV genotype-2a/3a patients. Recruitment is currently underway for this added cohort.

"The rapid 3.5 to 3.7 log10 HCV RNA reductions observed with PPI-668 at the three higher dose levels and the encouraging safety profile support advancement of PPI-668 to Phase 2 combination studies with other promising HCV antiviral agents," said Nathaniel A. Brown, M.D., Presidio's Chief Medical Officer. "The PK profile of PPI-668 appears to be a major factor in its efficacy profile, with rapid achievement of potentially effective plasma levels and with inter-dose plasma concentrations exceeding those needed to inhibit both wild-type HCV and many naturally-occurring HCV variants."

Detailed results of the completed trial are expected to be presented at a scientific meeting in the fall of 2012.

About Hepatitis C

Chronic hepatitis C is a progressive inflammatory liver disease caused by chronic infection with the hepatitis C virus (HCV). Approximately 170 to 200 million persons have chronic HCV infection worldwide, resulting in more than 350,000 deaths annually.

The current standard treatment for patients with hepatitis C genotype-1 infection in the United States and several other countries is combined administration of pegylated-interferon-alfa, ribavirin, and an HCV protease inhibitor. This treatment is characterized by incomplete efficacy and severe side effects in some patients.

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 focused on the discovery and development of novel oral antiviral therapeutics. For more information, please visit our website at: www.presidiopharma.com

SOURCE: Presidio Pharmaceuticals, Inc.

BMC Gastroenterology: More evidence that Hepatitis C resistance is linked to insulin resistance

Now online at Biomedcentral.com, a provisional article  (available in PDF version) to be published in BMC Gastroenterology, entitled "Hepatitis C virus E2 protein involved in insulin resistance through an impairment of Akt/PKB and GSK3beta signaling in hepatocytes".  This study is only part of a growing body of evidence supporting that the Hepatitis C virus is indeed associated with Type II diabetes through a variety of possible physiological mechanisms, most of which I willingly admit I don't understand.  If someone is willing to sit down and teach me this stuff as if I were a kindergartner, I would gladly accept. 



Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3beta signaling in hepatocytes
Ming-Ju Hsieh, Kuang-Ping Lan, Hao-Yu Liu, Xiao-Zong Zhang, Yaw-Feng Lin, Tzy-Yen Chen and Hui-Ling Chiou

BMC Gastroenterology 2012, 12:74 doi:10.1186/1471-230X-12-74

Published: 21 June 2012

Abstract (provisional)

Background

Hepatitis C virus (HCV) infection may cause liver diseases of various severities ranging from primary acute infection to life-threatening diseases, such as cirrhosis or hepatocellular carcinoma with poor prognosis. According to clinical findings, HCV infection may also lead to some extra-hepatic symptoms, including type 2 diabetes mellitus (DM). Since insulin resistance is the major etiology for type 2 DM and numerous evidences showed that HCV infection associated with insulin resistance, the involvement of E2 in the pathogenesis of type 2 DM and underlying mechanisms were investigated in this study.

Results

Results showed that E2 influenced on protein levels of insulin receptor substrate-1 (IRS-1) and impaired insulin-induced Ser308 phosphorylation of Akt/PKB and Ser9 phosphorylation of GSK3beta in Huh7 cells, leading to an inhibition of glucose uptake and glycogen synthesis, respectively, and eventually insulin resistance.

Conclusions

Therefore, HCV E2 protein indeed involved in the pathogenesis of type 2 DM by inducing insulin resistance.

Competing interests: The authors declare that they have no competing interests

Authors' Contributions:

Ming-Ju Hsieh has made substantive intellectual contributions to a published study and drafted the manuscript.

Kuang-Ping Lan, Hao-Yu Liu, Xiao-Zong Zhang and Yaw-Feng Lin have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data.

Shun-Fa Yang and Hui-Ling Chiou conceived of the study, and participated in its design and coordination and helped to draft the manuscript.

All authors read and approved the final manuscript.

Medgenics scores Orphan Drug designation for Infradure Hepatitis D indication...

Press release posted 6/21/12 on Reuters.com. A victory for Medgenics Infradure and their proprietary proprietary tissue-based Biopump platform technology which uses a biopsy of the patients own skin to deliver therapeutic proteins currently delivered via injection. The FDA has designated Infradure an orphan drug for the treatment of Hepatitis D here in the States, while clinical trials are ongoing in Israel for other indications, most notably, for Hepatitis C. This orphan drug designation doesn't ensure the FDA will grant Infradure an expedited review, but clearly that is a probability which could speed Infradure to market for a Hep D indication while trials for the remaining targeted indications carry on. 


CEO Sees FDA's Designation as Significant Validation of Medgenics' Novel Technology for Treatment of hepatitis D

Thu Jun 21, 2012 11:05am EDT

In near record time, Andrew L. Pearlman, Ph.D., President and Chief Executive Officer of Medgenics (AMEX:MDGN) has helped position his relatively new publicly traded company at a much higher level-- one that most other biotech firms usually take far longer to reach.

Earlier this week on Tuesday, his firm raised $9.5 million via a Private Placement and twenty-four hours later, he announced that Medgenics' INFRADURE(TM) for the treatment of hepatitis D had received Orphan Drug Designation from U.S. regulators at the FDA.

The significant news effectively made every protein therapy and hepatitis drug developer (not to mention investors) looks up and take notice.

"We see this as a really significant validation of our technology by the world's toughest regulatory agency," explains Pearlman. "This coming literally just a month after the FDA approved our first clinical trials- which went straight to Phase IIB- in the United States."

Asked to explain the significance of having achieved this designation for Medgenics' proprietary tissue-based Biopump(TM) platform, Pearlman doesn't miss a beat.

"First of all, Orphan Status is a very really significant milestone for any company in pharma or biotechnology," Pearlman says. "Because Orphan Drug Status means that the FDA recognizes that the treatment that you're developing is promising and looks like it can address the need for a specific patient population base."

Medgenics has been diligently developing the same proprietary tissue-based Biopump(TM) platform technology for the sustained production and delivery of therapeutic proteins using the patient's own skin biopsy for the treatment of a range of chronic diseases including anemia, hepatitis C and hemophilia among others. Pearlman believes this approach has multiple benefits compared with current treatments, which include regular and costly injections of therapeutic proteins and if he's right, his firm may have just taken one giant step toward convincing the rest of the world he was right.

"The reason why this is so important for our Company is that this is the first Orphan designation that we've attained for the use of our Biopump(TM) system and the beauty of this situation for us is that with Orphan designation, often what happens is that firms are granted an accelerated approval path by the FDA and although that's not guaranteed, we feel we have a good chance and are certainly hoping for that. Also, after a designation like this, the actual size of the clinical trials one needs to conduct is usually considerably smaller than you have to do for any of the major indications," says Pearlman.

"In Israel, we are hoping to be approved to commence the studies of our Biopump(TM) technology in Hepatitis C. Now Hepatitis C is an enormous indication. One hundred and eighty million people in the world have it and the INFRADURE Biopump(TM) has a very appealing and advantageous value proposition for the treatment of hepatitis C. It has an even more, I would say, compelling case for treating hepatitis B and there are some 350 million patients in the world with hepatitis B. All of these indications would use the same INFRADURE Biopump(TM) approach. The Biopump(TM) stimulates your body's immune system to fight the viral infection- whether its hepatitis B, C or D. The advantage of the combined approach that we're doing in going after hepatitis D as an orphan drug in the United States while commencing the clinical testing in hepatitis C in Israel is that we believe that we will demonstrate safety and efficacy in both of these indications, but that in the case of hepatitis D, there is a very improved likelihood for a relatively rapid route to a product approval compared to hepatitis B or hepatitis C-in which there would likely be much larger clinical trials and a longer path toward approval."

Following a late morning confirmation about the FDA news, shares of the company soared 25.36% to $8.65 +1.75 during regular market hours and headed higher in early trading on Thursday. If trading has been any indication thus far, the low-float stock may continue to appreciate in value as the market continues to digest the significance of the news. Particularly since some of Big Pharma's recent buyouts have targeted Drug makers developing hepatitis treatments.

Even some which have shown, arguably, less promise and innovation than Medgenics' own novel platform-- which aims to reduce some of the terrible side effects many patients endure with other treatments-have been acquired at huge premiums

Pearlman is focused on making sure that his firm will continue to build its pipeline and add value beyond its current $83.73 million market cap by executing and continuing to share positive developments like this one with investors.

"This is now the second approval that we've gotten for our technology, for our company and we think it will give a lot more confidence to would-be partners and institutional investors who may have been looking for a clear sign from a regulatory agency that we have a straight shot for an approvable product within a reasonable time."

Are HCV NS5A inhibitors as potent as we thought?

Posted on 6/20/12 on Pharmalot.com. Commentary on a change in protocol in BMS's COMMAND-3 trial for it's NS5A inhibitor daclatasvir by Pharmalot's Ed Silverman. BMS has restricted future enrollment for the trial to include only genotype 1b - a big statement in that 80% of genotype 1 (the most dominant genotype of HCV in the US) are of the 1a subtype. Does this mean there has been some virologic breakthrough in genotype 1a subjects in the COMMAND-3 trial? Hard to say, but the change in inclusion criteria has cast some doubt on the NS5A class. We'll have to wait for further data to see how this plays out. 

Bristol Hep C Trial Change Has Big Implications

By Ed Silverman // June 20th, 2012 // 8:02 am

Is a promising new class of drugs for treating hepatitis C going to be limited because patients with the most common genotype of the virus are likely to develop resistance to the medications? This is the possibility raised by a Wall Street analyst after learning that Bristol-Myers Squibb last week altered the protocol for a clinical trial for its daclatasvir antiviral, which is believed to be the most potent in the forthcoming NS5a class of hepatitis c treatments.

According to ClinicalTrials.gov, the drugmaker changed the protocol to its COMMAND-3 trial, which compares its drug in combination with interferon and ribavirin to Incivek, a protease inhibitor sold by Vertex Pharmaceuticals, along with interferon and ribavarin. What was the change? Bristol-Myers restricted future enrollment to patients who have only genotype 1b HCV, rather than all genotype 1 patients (see this and this).

“This effectively eliminates from the trial the most common HCV genotype in the US – 75 percent of HCV is genotype 1 in the US, 80 percent of genotype 1 is genotype 1a,” Sanford Bernstein analyst Tim Anderson writes in an investor note. “This change, some three months after the study started enrollment, suggests that some form of virologic failure has emerged in the patients with these genotypes… The NS5a class, as a whole, might be limited by the propensity to rapidly develop virological resistance, and by significant differences in potency from one viral genotype to another.”

He adds that the change in the protocol has “major strategic and tactical implications” for the hot and fast-growing hepatitis C market. How so? Several drugmakers are developing NS5a treatments and the possibility that these drugs generate resistance to the virus may prompt changes in how different types of medications are combined and, consequently, alter various corporate strategies for drug development, alliances and dealmaking.

Take Gilead Sciences. The drugmaker is developing an NS5a, which has the code name of GS5885, as well as another that is a nucleotide inhibitor, or nuke, which Gilead calls GS7977 and believes could be the cornerstone of the first all-oral regimen for hepatitis C. Gilead, you may recall, acquired GS7977 last fall as part of its $11 billion acquisition of Pharmasset, a bet that has transformed the investor view of the drugmaker (back story).

Two months ago, results of a study that combined daclatasvir with GS7977 suppressed hepatitis C in most patients four weeks after completing treatment, raising hopes about the prospects for a therapy that does not involve an injectable medication. But further collaboration between the two drugmakers appeared uncertain, because Gilead indicated a preference for developing its own NS5a drug with GS7977 (see this).

However, as Anderson notes, the Gilead NS5a drug is less potent than daclatasvir, which “increases the risk for Gilead of sticking with GS5885. On the Bristol side, their ‘go-it-alone’ strategy may be developing a hole, increasing the urgency of incorporating daclatasvir into an all-oral combination with a potent resistance-fighting nuke such as GS7977. This collaboration appears to have become more important to both parties,” he writes.

Both drugmakers recently declined comment on this topic, although late last month, Bristol-Myers ceo Lamberto Andreotti renewed a call for Gilead to jointly develop their hepatitis C medications. We asked Bristol-Myers about the change in the trial protocol and will update you with any reply that we receive.

Looking ahead, Anderson sees greater potential for combination therapy that relies on three drugs, instead of two, including GS7977 from Gilead, since the response to NS5a drugs suggests there can be limitations to at least one of the agents that developers would want to use in a one-two punch. And he believes Gilead’s prospects for creating one “super-regimen” for all subtypes with GS7977 and GS5885 alone, or even with ribavirin, have fallen.

As for other drugmakers, the questions concerning the NS5a drugs may result in slightly extended utility for Incivek as well as Victrelis, another protease inhibitor that is sold by Merck. This also suggests additional jockeying surrounding the NS5a drugs being developed by Achillion Pharmaceuticals and Idenix Pharmaceuticals, since larger drugmakers may decide to adjust their strategies and portfolios in response to the changing dynamics of this class of treatments.

“All this incremental insight about the limitations of different classes means the portfolios of the committed participants in the field will likely need to be larger than previously anticipated,” Anderson opines. “If, indeed, the field migrates to a three-mechanism standard, then smaller companies with one or more relatively isolated drugs, will be even more compelled to accept offers from buyers, and those buyers are likely to also require even more compounds than they have today, increasing the pressure on them to secure the few remaining independent assets.”

Idenix hep C polymerase inhibtor shows promise in mid-stage study...

Posted 6/19/2012 on the Chicago Tribune website. Not a whole lot of info in this bare-bones press release, but it looks like Idenix's HCV polymerase inhibitor IDX184 is faring pretty well, at least with an n=31 in this mid-stage clinical trial in combo with P/R. More info to follow as soon as I can dig some up. 

Idenix hep C drug shows promise in mid-stage study
 
Reuters
4:34 p.m. CDT, June 19, 2012

(Reuters) - Idenix Pharmaceuticals Inc said interim data from a mid-stage trial on its experimental hepatitis C drug showed promise, sending its shares up 12 percent.

The drug, IDX184, was given to 31 patients in combination with the standard hep C treatments pegylated interferon and ribavirin.

Nine patients received the combination therapy for 12 extended weeks and were checked four weeks later for signs of the virus in the blood to determine if there was a sustained virologic response, or SVR.

All four patients in the 100 mg arm and four out of five patients in the 50 mg arm achieved a sustained virologic response four weeks after the completion of treatment.

Patients who did not have undetectable levels of virus at 4 weeks and 12 weeks automatically entered the 36-week combination therapy extended treatment phase which is ongoing, the company said.

Idenix shares rose 12 percent to $10.45 in extended trade, after closing at $9.37 on Tuesday on the Nasdaq.

(Reporting by Shailesh Kuber in Bangalore; Editing by Saumyadeb Chakrabarty)

First Annual Viral Hepatitis Congress program announcement...

Please visit www.viral-hep.org/ for more info. 

The Viral Hepatitis Congress, 7-9 September 2012

The first annual Viral Hepatitis Congress is scheduled to take place 7-9 September 2012 in Frankfurt, Germany at Goethe University. Viral Hepatitis Congress has been developed following broad demand from various scientific and industry groups that there was need for an international meeting in Hepatitis in general, with a strong scientific focus on research and therapy but also with a strong international and commercial flavour in this fast moving sector.

The Viral Hepatitis Congress Scientific Committee, co- chaired by Professor Ira Jacobson and Professor Stefan Zeuzem under the auspices of Weill Cornell Medical College and Goethe University respectively have collaborated to develop a highly relevant and exciting programme. Furthermore, an event that should become an annual milestone for the exchange of information and ideas amongst the scientific community as well as forming a valuable forum for pharmaceutical and other companies with products and data in Hepatitis. There will be various output opportunities including webcasts but accepted abstracts will also be published as a journal supplement in the Journal of Viral Hepatitis.

1. Although we now have a largely completed roster of sponsors there are some further sponsor opportunities and if you would be interested please send me an email sophie.lea@kp360group.com.

2. Secondly if you have any suggested or desired delegates including yourself please let us know and we will be happy to assist in their registration

You can find the full draft programme and faculty at www.viral-hep.org

Achillion Pharmaceuticals names ex-Vertex CCO to it's board of directors...

Posted on 6-11-12 on MarketWatch.com. True HCV Drug Development nerds will recognize Kurt Grave's name from his tenure as Executive Vice President, Head of Corporate and Strategic Development and Chief Commercial Officer at Vertex Pharmaceuticals from 2007 to 2009 - no easy task to take a small, primarily R&D company and ready it for commercialization. His tenure abruptly ended at Vertex as he and then-CEO Matthew Emmens butted heads. Some of you might argue with me, but it seems like Vertex could use Grave's leadership skills given the company's current level of dysfunction and dissatisfaction with it's current leadership.  Mr. Graves replacing Nicholas Simon on the Achillion board could also be interpreted in multiple ways, following the leadership shakeup when CMO Elizabeth Olek resigned last week.

PRESS RELEASE
June 11, 2012, 4:03 p.m. EDT
Achillion Appoints Kurt Graves to Its Board of Directors

NEW HAVEN, Conn., Jun 11, 2012 (GlobeNewswire via COMTEX) -- Achillion Pharmaceuticals, Inc. ACHN +0.65% today announced the appointment of Kurt Graves to its board of directors as an independent director. Mr. Graves brings more than two decades of experience in building, leading and advising top-performing pharmaceutical and biotechnology companies. Mr. Graves was appointed as a Class I director, with a term expiring in 2013, and will replace Nicholas Simon of Clarus Ventures LLC.

"We are very pleased to have Kurt join the Board of Directors, as his extensive strategic knowledge of hepatitis C and successful career in transforming pharmaceutical companies complements the expertise of the entire Achillion Board," commented David I. Scheer, Chairman of the Board of Achillion. "From his tenures at Merck, Novartis and Vertex Pharmaceuticals, Kurt brings a depth of industry expertise and a global business view that will serve us well as we move toward achieving a number of aggressive milestones including the initiation of all-oral, interferon-free clinical trials evaluating regimens containing our pan-genotypic protease inhibitor, ACH-1625, and NS5A inhibitor, ACH-3102, for the treatment of HCV."

Michael Kishbauch, President and Chief Executive Officer of Achillion further commented, "On behalf of the Board of Directors, I would also like to thank Nick Simon for his insight and guidance over the past three and a half years as Achillion matured into a clinical-stage pharmaceutical company, with a portfolio of proprietary hepatitis C compounds discovered by Achillion and advanced into clinical development."

Mr. Graves currently serves as Chairman, President and Chief Executive Officer of Intarcia Therapeutics. He is also Chairman of the Board of Radius, since April 2011, and a Director of Pulmatrix and Springleaf Therapeutics, since May 2010. In addition to his global experience in large pharmaceutical companies, Mr. Graves has played key leadership roles in building two highly successful early stage companies; at Astra Merck Pharmaceuticals and Vertex Pharmaceuticals. Mr. Graves was EVP, Head of Corporate and Strategic Development and Chief Commercial Officer at Vertex Pharmaceuticals from 2007 through 2009. Prior to his tenure at Vertex, he spent nearly ten years at Novartis Pharmaceuticals in senior leadership positions of increasing responsibility, and was most recently Global Head of the General Medicines Business Unit & Chief Marketing Officer for the Pharmaceuticals division. Prior to Novartis, Mr. Graves held commercial and general management positions of increasing responsibility at Merck and Astra Merck Pharmaceuticals where he led the GI Business Unit, with responsibility for Prilosec and Nexium.

Mr. Graves earned his B.S. in Biology from Hillsdale College and has attended executive leadership programs at Harvard, Wharton School of Management and University of Michigan.

About HCV

The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide including more than 5 million people in the United States, more than twice as widespread as HIV. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Forward-Looking Statements

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 important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to the expected contributions of Mr. Graves to the Achillion Board of Directors and Achillion's expectations with respect to milestone achievement, and, in particular, its plans to initiate all-oral, interferon-free clinical trials evaluating regimens containing ACH-1625 and ACH-3102 for the treatment of HCV. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage nonclinical studies and clinical trials of ACH-2684, ACH-1625 and ACH-3102; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Achillion Pharmaceuticals, Inc.



        CONTACT: Company Contact:
        Glenn Schulman
        Achillion Pharmaceuticals, Inc.
        Tel. (203) 624-7000
        gschulman@achillion.com
        Investors:
        Mary Kay Fenton
        Achillion Pharmaceuticals, Inc.
        Tel. (203) 624-7000
        mfenton@achillion.com
        Media:
        Christin Culotta Miller
        Ogilvy PR
        Tel. (212) 880-5264
        Christin.Miller@Ogilvy.com

Bionor Pharma ASA files International Patent Application for Vacc-HCV for therapy & prevention of HCV...

Press release posted 6/7/2012 on Market Watch.com. Norway's Bionor Pharma files IPA for its peptide-based vaccine technology, including Vacc-HCV for potential treatment and prevention of HCV.

International Patent Application Submitted Covering Vaccines for Influenza (Universal Vaccine), Hepatitis C, Cytomegalovirus and Human Papillomavirus

OSLO, NORWAY, Jun 07, 2012 (MARKETWIRE via COMTEX) -- Bionor Pharma ASA (oslo:BIONOR)

News Summary
The new patent filed 6 June aims to strengthen the Company's general protection of its peptide based vaccine technology, including four specific product patents:

     
        --  Vacc-Flu is a universal influenza vaccine that researchers believe
            could produce long lasting immunity, and be effective for all seasonal
            variations of influenza A.
     
     
        --  Vacc-HCV is a vaccine that may be effective both as a therapy and for
            prevention of chronic liver infection. Hepatitis C (HCV) may lead to
            liver failure and liver cancer.
     
     
        --  Vacc-CMV is a vaccine for treating cytomegalovirus (CMV) infection,
            which has been associated with inflammatory diseases as well as
            aggravating various cancer forms such as brain tumors and prostate
            cancer.
     
     
        --  Vacc-HPV is a vaccine for treating throat and vaginal cancer caused by
            Human papillomavirus (HPV).
     
     
 
Bionor Pharma ASA (oslo:BIONOR) announced today that it has initiated the international patent process for further protection of the Company's peptide vaccine technology platforms, and for the vaccine candidates Vacc-Flu, Vacc-HCV, Vacc-CMV and Vacc-HPV. This new peptide vaccine platform submission complements the two previously filed technology platform patents covering peptide vaccines designed for generation of antibody responses and peptide vaccines designed for generating T-cell responses.

All the vaccine candidates are developed from conserved parts (proteins) of the respective viruses. By applying the platform technology to modify the peptides, the vaccines are shown to have significantly improved immune response properties as compared to the corresponding unmodified (native) peptides.

The new platform patent is also covering protection of the various administration regimes connected to the vaccines. Preclinical research is ongoing for both the influenza and the HCV vaccines.

About Vacc-Flu Developing a "universal" influenza vaccine has been difficult because influenza viruses undergo constant genetic mutation. Vacc-Flu targets conserved regions, the "Achilles' Heels" that are common to all known Influenza A viruses. The vaccine is designed to provide long-term protection over several years, reducing deaths and related illnesses caused by all current influenza A subtypes, as well as future influenza viruses that may emerge and lead to an influenza pandemic. Vacc-Flu has shown in animal studies to reduce serious flu symptoms by 25 percent over the standard flu vaccine.

"The benefits of a universal vaccine far outweigh the current seasonal vaccine development approach," said Steen Kroyer, CEO, Bionor Pharma. "The goal is to eliminate the need for researchers to develop annual vaccines, a challenging process that requires manufacturers to operate on a tight schedule to meet WHO recommendations."

The global market for an influenza vaccine is approximately 250 million doses corresponding to annual sale of approximately $2 billion to $2.7 billion. Today's influenza vaccines are specific only for one season and new vaccines have to be developed each year.

About Vacc-HCV Bionor's therapeutic vaccine for hepatitis C, Vacc-HCV aims to treat chronic HCV infection that affects the liver and may lead to scarring and cirrhosis with liver failure or liver cancer in advanced disease.

An estimated 150 million people are living with chronic hepatitis C and between three and four million people become infected per year. Over 350,000 deaths annually are attributed to hepatitis C-related diseases.

Although new drugs are expected to enter the market, these treatments will not be without side effects and treatment failures. This opens the door to even better stand-alone therapy or combination therapies, including a therapeutic vaccine.

About Vacc-CMV Bionor's therapeutic CMV vaccine targets diseases associated with cytomegalovirus (CMV) infection. Researchers believe that CMV may not itself be the disease causing agent, but that it aggravates disease by changing the environment, resulting in a weakened immune system. Thus CMV may be a contributing factor to inflammatory diseases or tumor growth. In a number of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis, active CMV infection can be detected. In various cancer forms such as prostate, colon, breast and brain cancer, CMV can be detected in the tumor but not in the nearby tissue.

Vacc-CMV will be developed as a therapeutic T-cell (killer cell) vaccine for treatment of CMV positive patients with inflammatory diseases or cancer.

About Vacc-HPV The Human papillomavirus is made up of a group of DNA viruses in the family Papillomaviridae that infect the skin and mucous membranes causing genital warts, cervical cancer and a growing number of throat cancer cases. Worldwide, cervical cancer remains the second most common malignancy in women, and is a leading cause of cancer related death for females in developing countries. Company researchers believe Vacc-HPV will be a therapeutic T-cell (killer cell) vaccine aiming to complement today's standard of care.

About Bionor Pharma ASA Bionor Pharma is a leading vaccine company, listed on the Oslo Stock Exchange. The Company's investments in developing therapeutic vaccines exceed US$70 million.

Bionor's vaccines are based on the proprietary technology platform developed following more than two decades of research on peptides. The vaccines are designed to safely activate each person's immune system to combat viral diseases. The Company's lead HIV vaccine, Vacc-4x, is being investigated as a therapeutic vaccine, and has completed a phase 2b randomized, multinational (USA and 4 European countries), double-blind, placebo-controlled trial. It produced a statistically significant reduction in viral load and viral load set point by killing of virus producing cells.

Bionor's second therapeutic HIV vaccine, Vacc-C5, is developed to induce antibodies to HIV that can reduce viral production (lowering the set point) and the harmful hyperactivation of the immune system that leads to AIDS. Recently, the clinical phase I/II study with Vacc-C5 was approved by the Norwegian Clinical Board. Subsequent to the Vacc-C5 phase I/II trial, Bionor intends to combine Vacc-4x with Vacc-C5, which could form the basis for both a therapeutic and a preventative HIV vaccine.

The Company's innovative technology platform is also well suited to develop vaccines for other viral diseases, including Influenza, HCV (Hepatitis C), CMV (Cytomegalovirus) and HPV (Human papillomavirus).

More information about Bionor Pharma, its research and products, is available at www.bionorpharma.com .

This information is subject of the disclosure requirements acc. to Section 5-12 vphl (Norwegian Securities Trading Act). Vacc-4x, Vacc-C5, Vacc-Flu, Vacc-HCV, Vacc-CMV and Vacc-HPV are investigational treatments that have not been approved for marketing by any regulatory authority.

        Bionor Pharma ASA, Oslo: +47 23 01 09 60
        Bionor Pharma laboratories: +47 35 90 85 00
        Steen Kroyer
        CEO
        Birger Sorensen
        EVP, Head of Vaccines
     
        USA Contact:
        David Sheon
        202 422-6999
        Email Contact
     
        SOURCE: Bionor Pharma

Senator asks for SEC investigation into Vertex Pharmaceuticals executive stock sales...

Posted on 6/7/12 on Bloomberg.com. Could be one of the many reasons Vertex is leaking executives lately, including less-than-forecast Telaprevir sales through week 8 of Q2.

Grassley Questions Timing Of Vertex Stock Sales In Letter

By Drew Armstrong - Jun 7, 2012 2:00 PM PT

Senator Charles Grassley asked U.S. regulators to probe whether Vertex Pharmaceuticals Inc. executives profited unfairly from stock sales before corrected drug data sent shares down.

Calling the sales “a potentially troubling issue for investors in the pharmaceutical industry and for the federal government,” Grassley wrote Securities and Exchange Commission Chairwoman Mary Schapiro to ask her to look into share sales by five company executives and two board members.

Vertex gained 55 percent on May 7 after the company said a study of its experimental cystic fibrosis drug VX-809 combined with Kalydeco helped patients’ breathing. On May 29, the shares fell the most in three years after the Cambridge, Massachusetts- based company revised those results, saying the therapy wasn’t as effective as claimed.

“It could appear that these Vertex (VRTX) executives potentially took advantage of the spike in the stock knowing the news of the clinical data being overstated would be made public eventually, which in turn would negatively affect the stock value,” Grassley said in his letter, dated today.

The executives and two board members got rid of their shares from May 7 to May 29, as part of timed sales, according to Grassley’s letter. He has asked for an answer from the SEC by June 28.

Vertex spokesman Zach Barber said that the share sales had been scheduled ahead of time according to a pre-planned shares process, and that Vertex disclosed the correction to the data quickly.

“All shares sold by our executives and directors were either part of pre-existing 10B5-1 plans or followed Vertex’s internal stock trading policy,” Barber said in an e-mail.

Shares Decline
Vertex shares fell 1.1 percent to $56.77 at the close in New York. The company has gained 4.8 percent in the past 12 months.

Grassley could open his own investigation of the stock sales. The Iowa senator has used his position as the top Republican on the Senate Judiciary Committee and a member of the Senate Finance Committee to investigate potential wrongdoing by health-care companies in the past.

Vertex said on May 29 that a misinterpretation between Vertex and an outside data-analysis firm led to the correction. It doesn’t affect Vertex’s plans to start final-stage trials for U.S. marketing approval, Chief Executive Officer Jeffrey Leiden said on a conference call that day.

John Nester, an SEC spokesman, said the agency had received the letter but declined to comment on its substance.

To contact the reporter on this story: Drew Armstrong in New York at darmstrong17@bloomberg.net;

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

Achillion Announces Resignation of Chief Medical Officer...

Press release posted 6/6/2012 on Market Watch.com:  

Achillion Announces Resignation of Chief Medical Officer

NEW HAVEN, Conn., Jun 6, 2012 (GlobeNewswire via COMTEX) -- Achillion Pharmaceuticals, Inc. ACHN +2.86% today announced the resignation of Elizabeth A. Olek, D.O., Senior Vice President of Clinical Development and Chief Medical Officer, effective June 18, 2012. Milind Deshpande, Ph.D., President of Research and Development and Chief Scientific Officer, will assume responsibility for the oversight of ongoing and planned clinical trials evaluating Achillion's portfolio of compounds for the treatment of hepatitis C (HCV).

"Achillion's clinical programs have matured extensively during Liz's tenure, and during that time, our robust pipeline of HCV compounds, focused on pan-genotypic protease inhibitors and NS5A inhibitors, has advanced from discovery into early and mid-stage clinical trials. We thank Liz for her significant contributions to that development progress and wish her the best of luck in her future endeavors," said Michael D. Kishbauch, President and Chief Executive Officer of Achillion.

Mr. Kishbauch further commented, "As we move toward initiating all-oral clinical trials evaluating the combination of our protease inhibitor, ACH-1625, and our second-generation NS5A inhibitor, ACH-3102, later this year, we are confident that our development plans will remain on track by leveraging the talents of Dr. Deshpande, as well as physicians on both our staff and on our Board of Directors, and we plan to continue to achieve our aggressive milestones."

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Forward-Looking Statements

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 important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: Achillion's plans to initiate all-oral clinical trials evaluating the combination of ACH-1625 and ACH-3102, its beliefs that its development plans will remain on track by leveraging the talents of Dr. Deshpande and others, and its plan to continue to achieve its aggressive milestones. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage preclinical studies and clinical trials of ACH-1625 and ACH-3102; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; retain key employees; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Achillion Pharmaceuticals, Inc.



        CONTACT: Company Contact:
        Glenn Schulman
        Achillion Pharmaceuticals, Inc.
        Tel. (203) 624-7000
        gschulman@achillion.com
        Investors:
        Mary Kay Fenton
        Achillion Pharmaceuticals, Inc.
        Tel. (203) 624-7000
        mfenton@achillion.com
     


(C) Copyright 2010 GlobeNewswire, Inc. All rights reserved.

Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C...

Article-In-Press published online 5-28-12 on the Journal of Hepatology website.  Interesting study that finds higher insulin resistance in non-diabetic HCV-subjects that have the T/T and T/C-allele than their CC allele counterparts. IR, along with fibrosis and steatosis, have been established predictors of response to PEG + Ribavirin therapy - Insulin resistance could be one factor that explains the the difficulty in treating HCV patients with IL28B TT and TC genotypes. 

Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C

Albert Friedrich Stättermayer, Karoline Rutter, Sandra Beinhardt, Thomas-Matthias Scherzer, Andreas Stadlmayr, Harald Hofer, Fritz Wrba, Petra Steindl-Munda, Michael Krebs, Christian Datz, Michael Trauner, Peter Ferenci

Received 29 December 2011; received in revised form 20 March 2012; accepted 5 April 2012. published online 28 May 2012.
Accepted Manuscript

Abstract
Background /aims
Insulin resistance, fibrosis and steatosis are established predictors of response to peg-interferon/ribavirin therapy in chronic hepatitis C (CHC). Several host genetic polymorphisms (IL28B, PNPLA3) modify treatment-outcome, the degree of steatosis or fibrosis. The aim of our study was to evaluate the role of these polymorphisms on insulin resistance in treatment-naïve patients with chronic hepatitis C.

Methods
202 non-diabetic CHC patients (GT1: 181, GT4: 21; m=126, f=76) undergoing liver biopsy in two tertiary academic centers were studied. The SNPs rs12979860 (IL28B) and rs738409 (PNPLA3) were investigated by RT-PCR. HOMA-IR, BMI, stage of fibrosis, extent of steatosis and genetic data were analyzed.

Results
Insulin resistance (HOMA-IR3.0) was associated with the rs12979860 genotype, presence of advanced fibrosis and higher BMI. HOMA-IR in CC and in TC/TT was 2.08±1.61 (mean±SD) and 2.94±2.89 (P=.041), respectively. HOMA-IR was higher in advanced than in mild fibrosis (F3-4: 3.92±3.15; F0-2: 2.38±2.38; P=.004). The percentage of steatotic hepatocytes was greater in patients with advanced fibrosis (21.3±21.5 vs. 9.1±14.2; P<.001), HOMA-IR3.0 (17.7±17.8 vs. 8.8±15.4%; P<.001) and BMI>25.0kg/m2 (14.7±17.0 vs. 9.1±16.1; P<.001). The rs738409 GG genotype was associated with advanced fibrosis and steatosis, but not with HOMA-IR. Multivariable logistic regression identified advanced fibrosis (OR: 2.820, 95%CI: 1.344-5.917; P=.006) and the IL28B genotype non-CC (OR: 3.000, 1.348-6.676; P=.007) as independent risk factors for insulin resistance.

Conclusion
Insulin resistance is more common in carriers of the T-allele of SNP rs12979860 than in CC homozygotes and may partly explain the poor outcome of peginterferon/ribavirin therapy in these patients.

Abbreviations: CHC, chronic hepatitis C, HCV, hepatitis C virus, HOMA, homeostasis model of assessment, IR, insulin resistance, IL28B, interleukin 28 B, PNPLA3, patatin like phospholipase domain-containing 3, SVR, sustained virologic response, SNP, single nucleotide polymorphism, T2DM, type 2 diabetes mellitus

Vertex receives FDA warning letter on 'misleading branded story'...

Article posted 5/31/12 on Regulatory Focus.com.  Vertex brushes with the FDA over what the FDA considered to be a 'misleading branded story'.  The timing isn't great as Vertex supposedly is getting ready to amend it's labeling, possibly to include BID dosing. 

‘Misleading’ Patient Perspective Smacked Down by FDA in Untitled Letter
Latest News | Posted: 31 May 2012

By Alexander Gaffney

One pharmaceutical company is learning this week that reproducing a patient’s story to “mentor” other potential patients may not sit well with US regulatory authorities, regardless of whether it represents the patient’s perspective accurately.

Cambridge, Massachusetts-based manufacturer Vertex Pharmaceuticals was sent an Untitled Letter by the US Food and Drug Administration (FDA) warning it about its promotion of Incivek (teleprevir), a Hepatitis C (HCV) drug which FDA said was being marketed using a “misleading” branded story.

The branded story is told through the eyes of a patient, “JP”, who tells the audience of his struggle with HIV and subsequent—but difficult—success using Vertex’s Incivek, which he claims “cleared the virus” from his body.

FDA explained in its 25 May letter that Vertex has “overstated” the efficacy of Incivek because it suggests the drug is more effective than “substantial evidence or substantial clinical experience” has shown.

“While these claims may be an accurate reflection of James’ own experience with hepatitis C and treatment with Incivek, this branded story misleadingly implies that most or all cirrhotic prior null responders infected with hepatitis C will successfully achieve Sustained Virologic Response (SVR) on Incivek combination therapy,” wrote FDA in the Untitled Letter. “FDA is not aware of substantial evidence or substantial clinical experience to support this implication.”

Put succinctly, “one patient’s treatment response does not constitute substantial evidence,” said FDA. Further, FDA said the testimonial “misleadingly implies removal of HCV from the body, when this is not the case.” Instead, the virus may well have simply become undetectable while continuing to replicate, noted FDA.

The testimonial also minimized important risk information by downplaying the side effects of the drug, explained FDA. The testimonial recounts “JP” receiving the treatment, which caused him to lose significant amounts of hair and develop a rash. “But that was nothing,” said “JP,” referring to the side effects relative to the benefits of the treatment for him. FDA maintains this “minimizes the risk” of both side effects, and particularly the risks of the rash, which the agency called “serious.”

FDA called on Vertex to stop using the branded story and respond to FDA’s Untitled Letter within 15 days.

A Vertex spokeswoman, Nikki Levy, told The Boston Globe the company has never distributed the story and was now working to revise its content in light of FDA’s informal warning.

Untitled letters are different from official FDA Warning Letters in that they do not include a list of potential agency enforcement actions and are generally less serious than are formal Warning Letters.

BMS urges HCV combo study with Gilead Sciences...

Lovingly pinched from the mighty NATAP.org. BMS calling out Gilead to collaborate at the at the Sanford Bernstein Strategic Decisions Conference in New York, after the success of Gilead's GS-7977 and Bristol's daclatasvir combination in HCV treatment-naive patients presented at EASL. Gilead seems content to use their own, proprietary NS5A inhibitor in combo with GS-7977 thus far, however. 

Bristol urges combo hepatitis C study with Gilead

By Ransdell Pierson

Thu May 31, 2012


(Reuters) - Bristol-Myers Squibb Co renewed calls for biotechnology company Gilead Sciences Inc to test one of its hepatitis C drugs in late-stage trials alongside Bristol's own promising medicine, following impressive results from a mid-stage trial that combined the experimental products.

Bristol's daclatasvir is from a new class of drugs known as NS5A inhibitors. Gilead's GS-7977 is a nucleotide polymerase inhibitor. Both are designed to block enzymes essential to replication of the hepatitis C virus.

Bristol-Myers Chief Executive Lamberto Andreotti, speaking on Thursday at the Sanford Bernstein Strategic Decisions Conference in New York, said patients and both drugmakers stand to benefit if combined Phase III trials of the two medicines are pursued.

"We have a different point of view about whether to enter Phase III (trials) with that combination," Andreotti said. "We believe, for both patients and companies, it is better to move forward" in the short term.

But Andreotti said Gilead instead seemed intent on looking "in-house" -- focusing on combinations of its own products. Gilead officials could not immediately be reached to comment.

Andreotti said there was a "huge, unmet need" for better treatments among an estimated 170 million to 180 million people worldwide believed to be infected with the virus. Transmitted by blood transfusions, sexual contact or shared drug needles, the virus invades the liver and can steadily destroy the organ over decades. It is the most common reason for liver transplants in the United States.

Data from the mid-stage trial combining Gilead's GS-7977 and Bristol's daclatasvir showed a 100 percent response rate in previously untreated patients with the most common form of hepatitis C.

Shares of Gilead jumped 11 percent on April 19 when the data were released, showing the profound benefits of combining its 7977 -- acquired through Gilead's $11 billion purchase of Pharmasset -- with daclatasvir.

At the time, Bristol said Gilead had balked at further collaboration on the combination under study, which was begun while 7977 was owned by Pharmasset.

The results of the mid-stage study were accomplished without interferon, an injected drug that causes flu-like symptoms and other side effects that often lead patients to discontinue or delay treatment. Nor did the study use ribavirin, an older antiviral drug that is also currently part of all treatment regimens.

Instead of working with Bristol-Myers, Gilead is forging ahead with a study of 7977 in combination with its own experimental NS5A inhibitor. In the meantime, Bristol-Myers is testing daclatasvir with a drug similar to 7977 that it acquired with its $2.5 billion purchase of Inhibitex, as well as with other experimental drugs in its development pipeline.

In other remarks at the Sanford Bernstein meeting on Thursday, Andreotti said he expects some form of U.S. healthcare reform to emerge, even if the U.S. Supreme Court rules against extensive reforms approved by Congress and signed into law by President Obama.

The High Court is expected next month to render a decision on the sprawling legislation, which would greatly expand healthcare coverage to uninsured Americans but require bigger fees and rebates from drugmakers and medical device makers.

Andreotti said the enacted reforms "started out on the right foot" but became too complicated for Bristol-Myers and the American people.

The Bristol-Myers CEO said he expects rapidly declining sales of Plavix, a blood-clot preventer which has long been the company's biggest product, due to loss of U.S. patent protection earlier this month and ensuing competition from a number of cheaper generics. The pill, sold in partership with French drugmaker Sanofi, had revenue last year of more than $7 billion -- making it one of the world's top-selling medicines.

Despite expected plunging sales of Plavix, Andreotti said Bristol-Myers has no plans to "downsize" its research spending, having already closed down many company facilities in previous cost-cutting efforts.

Bristol-Myers will adjust future R&D spending in accordance with company performance, and expects significant sales gains to come from Asia but not from Europe, Andreotti said.

He said the company plans over the next few years to concentrate on developing medicines to treat cancer, viral infections and blood clots -- calling those therapeutic areas "the three pillars" of company growth.

(Reporting By Ransdell Pierson; Additional reporting by Bill Berkrot; Editing by Maureen Bavdek and Gunna Dickson)