BMS formally suspends development of BMS-094...

Posted 8/23/2012 on Fox Business.com.  BMS formally suspends development of nucleoside inhibitor BMS-094/INX-189 due to possible heart and kidney toxicity. One subject died, nine were hospitalized and two remain so at the time of press. The cause of the events has not yet been identified. Ramifications have already been felt through the HCV drug development space, with Idenix's IDX184 clinical trial, a nucleoside inhibitor similar in structure to BMS-094, put on partial clinical hold by the FDA. The FDA hinted in it's letter to Idenix that there were possibilities of similar actions to other nucs in development as well.

Bristol-Myers Discontinues Development of Hepatitis C Drug
Published August 23, 2012

Dow Jones Newswires

Bristol-Myers Squibb Co. (BMY) said Thursday it has discontinued the development of a drug intended to treat the liver disease hepatitis C in the interest of patient safety, after a patient died and others were hospitalized.

Bristol-Myers earlier this month voluntarily suspended a Phase 2 study of BMS-986094, which was formerly known as INX-189, a nucleotide polymerase inhibitor, or "nuke." The initial case of heart failure, which was the basis for halting the study, subsequently resulted in death, the company said Thursday.

Bristol-Myers said it is working with the U.S. Food and Drug Administration and clinical study investigators to conduct ongoing and close follow-ups of all the study's patients. To date, nine patients have been hospitalized, including the initial patient, and two remain hospitalized.

The company said the cause of these unexpected events, which involve heart and kidney toxicity, hasn't been definitively established.

Bristol-Myers decision to halt the study earlier this month raised questions about the experimental drug's potential and the $2.5 billion price tag Bristol paid earlier this year to buy the company that developed it. The suspension was considered a significant setback for the drug maker--already grappling with weak sales of its Plavix anticlotting drug that lost patent protection in May--in the race to develop new hepatitis C treatments.

Bristol-Myers as well as other companies such as Gilead Sciences Inc. (GILD) and Abbott Laboratories (ABT) has been looking to bring the first all-oral hepatitis C regimen to market, hoping to tap what is expected to be a multibillion-dollar market for such a therapy.

To strengthen its hepatitis C position, Bristol-Myers in February shelled out $2.5 billion to buy Inhibitex Inc. at a whopping 163% premium. Bristol was lured primarily by Inhibitex's nuke for hepatitis C, though it did acquire other potential treatments for infectious disease in the deal.

Treatments for hepatitis C are considered lucrative because the disease is prevalent in large sections of the global population. The virus, which can be transmitted sexually or through use of shared needles and at tattoo parlors, affects some 170 million people world-wide.

Separately, Synergy Pharmaceuticals Inc. (SGYP) said it has agreed to acquire the assets related to shingles treatment FV-100 from Bristol-Myers. FV-100 was developed by Inhibitex.

Shares were up by 10 cents to $32.25 after hours. The stock has fallen 8.8% since the start of the year.

-Write to Nathalie Tadena at nathalie.tadena@dowjones.com

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Copyright © 2012 Dow Jones Newswires

Seeking Alpha: Is The Hep C Drug Pipeline Beginning To Crack?

Posted on 8/19/12 on Seeking Alpha.com. Commentary by Tiran Rothman from Bioassociate Consulting on the current state of affairs in HCV drug development. His feeling is that the troubles with the NS5A inhibitors may give formerly dark horse companies developing drugs with differing approaches to tackle the virus (mentioned are BioLineRx with it's BL-8020 entry inhibitor and Transgene's TG4040 therapeutic vaccine) a chance to shine. 

Is The Hep C Drug Pipeline Beginning To Crack?

By Tiran Rothman

Another crack appeared today in the ultra-hype of next generation Hep C drugs. Idenix Pharmaceuticals (IDIX) released news that its Phase IIb trial with IDX184 was put on partial clinical hold by the FDA due to the recent cardiovascular toxicity experienced by a patient treated with a similar treatment developed by Bristol-Myers Squibb (BMY). Idenix's investors were quick to pull the trigger, sending the stock for a 40% nosedive.

Both Idenix's IDX184 and BMS's 094 are NS5 family inhibitors, which are the front line of Hep C drug candidates, destined to be part of an oral therapy regimen that will make the current use of interferon injections redundant. Even though there has been no evidence of cardiotoxicity in patients treated with IDX184, the FDA has expressed a concern regarding potential safety problems of the drug.

Gilead (GILD), the current leader in the next-gen Hep C drugs, is planning a Phase III study with a combination therapy of its NS5A and NS5B inhibitors. The FDA's recent caution regarding NS5 inhibitors might also affect Gilead's sprint toward the finish line. Novartis (NVS), which has recently joined the Hep C crowded waters with the $440m Enanta Pharmaceuticals deal, might also suffer from this new NS5-related safety issues.

About 180 million people worldwide are chronically infected with HCV. The global Hepatitis market was estimated at $6 billion in 2011 and is forecasted to grow to $20 billion until the end of the decade. The combination of this huge and growing market and insufficient efficacy of the current treatments has generated an immense interest among drug developers and quite a few deals.

The recent holdups in the NS5-related treatments suggest that the Hep C pipeline might need some variations. Several companies are developing alternative, non-NS5 inhibitor-related, Hep C treatments. Examples for such technologies are Transgene's (TRGNF.PK) TG4040 - a therapeutic Hep C vaccine based on a virus carrying and expressing three of the major Hepatitis C virus's non-structural proteins (NS3, NS4 and NS5B). TG4040 is currently in a phase II trial.

A different approach is taken by BioLineRx (BLRX) that develops BL-8020, an orally available treatment with a unique mechanism of action - inhibition of Hepatitis C virus-induced autophagy. In other words, BL-8020 acts on the host cell rather than the virus itself, thus greatly differentiating it from current and pipeline Hep C drugs. Preclinical studies have shown a synergistic effect of BL-8020, when combined with other anti-Hep C agents, which is likely to increase these agents' potency and reduce any adverse effects by enabling utilization of lower dosages.

With the current setbacks seen among Hep C pipeline frontrunners, additional rounds of licensing and acquisition deals in this area are expected, and companies that develop new and different approaches for Hep C treatment may greatly benefit from others' failures and should be closely watched by investors that follow this therapeutic field.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

IDX184 suffers setback in clinical trial....

Posted 8/16/12 on MarketWatch.com. Ouch. This makes Novartis look almost prescient in it's restructuring of it's relationship to Idenix. BMS-094, PSI-938 and IDX184 all share the same chemical structure - even if the cardiac event is unrelated to BMS-094 (hard to tell) I think the market will be wary regarding nucs sharing this structure.  

Idenix plunges 30% on HCV drug setback       08/16 10:43 AM

 BOSTON (MarketWatch) -- Shares of Idenix Pharmaceuticals (IDIX:$5.93,00$-2.38,00-28.64%) plunged 30% to $5.96 Thursday on news that the U.S. Food and Drug Administration has partially halted a Phase II clinical trial for its drug IDX184 over safety concerns. Idenix has been testing the product for the treatment of the hepatitis C virus, or HCV. The FDA placed a 'partial hold' on the trial pending the evaluation of reports that one of the patients taking the treatment had suffered a severe cardiac event. The FDA has also requested that Idenix provide additional patient data to help the agency with its evaluation. IDX184 belongs to a newer class of HCV drugs known as nucleotides. Earlier this month, shares of rival Bristol-Myers Squibb (BMY:$31.95,00$0.07,000.22%) slid almost 10% after the company announced it had suspended a Phase II study of its HCV nucleotide agent due to concerns that a patient had developed heart failure.

The Street.com: Rethinking Idenix Pharma in Wake of Bristol's Hep C Blow Up...

Posted 8/6/12 on The Street.com. The Streets's Nathan Sadeghi -Nejad weighs in on the current - and seemingly hyperactive - HCV drug development space. He's right, the last couple of weeks have been a whirlwind of surprises - Novartis giving Idenix the rights to it's HCV drugs back, BMS's BMS-094 seemingly taking it's last breath, Gilead co-formulating it's nuc with it's NS5A inhibitor just to name a few.  BMS has had a rough time of it in the HCV drug development space. It's $885 million purchase of ZymoGenetics with it's Peg Lambda seemed like a great move in 2010, before the advent of the idea of potential interferon-free therapy (I still think Peg Lambda may be a surprise dark horse - I'm still cautious on the potential 'interferon free' except in certain cases), Then consider the $2.5 billion purchase of Inhibitex, whence the doomed BMS-094 nuc came from leaving BMS's NS5A inhibitor without a BMS-owned partner. It's other late-stage HCV drugs aren't much to sneeze at. Ouch. Sadeghi-Nejad makes some other observations (Gilead - yes. Idenix - nuc is too close to BMS-094, maybe a toxicity issue but no safety signals to support. Vertex nuc looks powerful, but too far from market to mean much) that you may or may not agree with. Definitely a good read if you're watching the HCV drug development race.

Rethinking Idenix Pharma in Wake of Bristol's Hep C Blow Up

By Nathan Sadeghi-Nejad - 08/06/12 - 7:00 AM EDT
Tickers in this article: IDIX BMY GILD VRTX

NEW YORK (TheStreet) -- Last week, Bristol-Myers Squibb(BMY) confirmed my previously reported suspicions by abruptly halting a Phase II trial of BMS-094 (formerly INX-189) -- a nucleotide polymerase inhibitor, or "nuc," for the treatment of hepatitis C. One patient in the study experienced major cardiovascular toxicity, forcing Bristol-Myers to stop dosing BMS-094.

The company has provided few follow-up details but it appears as if BMS-094 is dead.

That means Bristol-Myers' $2.5 billion acquisition of Inhibitex (from where BMS-094 originated) has proven to be a complete zero in less than seven months. I'm not sure if that's a mergers-and-acquisition disaster record, but it's probably close.

The demise of BMS-094 has also reshaped the Hep C landscape. Let's review who still stands and where. For some assistance, I turned to John Tucker, a scientific analyst with BioMedTracker, a division of Sagient Research. Tucker recently published an excellent overview on Hep C drugs in development and he's been all over BMS-094 and its implications.

At this point, combining a "nuc" with an NS5A inhibitor and the generic antiviral drug ribavirin seems to be the most promising "all oral" Hep C regimen in clinical development. This makes Bristol-Myers' daclatasvir, an NS5A inhibitor essentially useless on its own. The company's other later-stage hep C drug candidates -- the non-nucleoside polymerase inhibitor BMS-791325 and the protease inhibitor asunaprevir -- have only modest efficacy or toxicity issues, or both.

Bristol-Myers may continue to beg but I'm convinced Gilead Sciences(GILD) has no interest in a daclatasvir partnership. As I noted recently, Gilead's nuc-NS5A combination -- GS-7977 and GS-5885 -- has made rapid clinical progress and will start pivotal trials this year. In sum, the BMS-094 blowup leaves Bristol-Myers up a proverbial creek in Hep C. Although this failure has little long-term financial impact, Bristol-Myers' apparent inability to foresee this compound's risks raises concerns about the company's R&D and business development capabilities.

Gilead emerges a big winner. I have long believed Gilead would be first to market with an all-oral Hep C regimen, but Bristol-Myers has handed the company a much bigger lead. (I also still doubt the size of the commercial market for Hep C, but that's another issue.)

I initially considered Idenix Pharmaceuticals(IDIX) and its nuc IDX-184 a winner emerging from the BMS-094 blowup. Now, I'm less sure.

IDX-184 has a chemical structure that is similar to both BMS-094 and Pharmasset's PSI-938, another Hep C nuc that was killed off by toxicity problems last year. More specifically, the active moiety of IDX-184 -- the part of the molecule that makes the drug work -- appears to be similar to the active moieties of both BMS-094 and PSI-938. That could be a big problem.

Chemists often attach nonessential atoms to a drug candidate in an attempt to change the compound's overall physiological behavior. As the drug is metabolized in the body, those byproducts are cleaved and the working core of the drug -- the active moiety -- is unveiled.

The byproducts are usually innocuous, but not always. For example, it's not clear whether the side effects that killed BMS-094 were caused by the active moiety or by 1-naphthol, a toxic metabolite of the drug. Similarly, PSI-938's fatal flaw remains unclear. This worries me, and it should worry Idenix bulls.

Idenix does have a very reasonable defense. Management contends IDX-184 is nearly entirely targeted to the liver and metabolized poorly in other cell types. Further, IDX-184 seems to be more slowly metabolized by the liver than BMS-094. These factors certainly lessen the risk of toxicity. Thus far, Idenix has treated roughly 60 patients for 12 weeks with IDX-184 and observed no safety signals, including no cardiovascular side effects.

That's encouraging, but I would prefer to overpay for Idenix after there are more data on IDX-184. I would reduce or eliminate long exposure to Idenix until the drug's safety has been more completely established.

Two more Idenix red flags that make me cautious: First, Novartis(NVS), Idenix's partner for nearly a decade, ended the relationship last week. I understand that Novartis wasn't much of a collaborator so walking away might actually be a net positive for Idenix. But I still tend to view pharma-biotech breakups as a negative, although in this case a bit less so.

Second, Idenix completed a major secondary offering only two days after the Novartis breakup. Idenix sold 22 million shares at $8.00 per share or 28% below recent highs. Although I generally support equity issuances at management's discretion, the company still had at least $90 million in the bank. Shareholders should feel justifiably frustrated at this seemingly unnecessary rush dilution of the existing investor base. I worry that the timing signals dark clouds on the horizon.

Right before the Bristol-Myers news, Vertex Pharmaceuticals(VRTX) announced impressive early clinical data for ALS-2200, a nucleotide analogue licensed from Alios BioPharma. After seven days of dosing, the eight treated patients showed a median 4.54 log reduction in viral load. That's near complete eradication of virus, for those of you unfamiliar with the logarithmic scale.

Unfortunately for Vertex, ALS-2200 has not cleared any meaningful long-term safety hurdles and the drug remains years behind Gilead's compounds. I would put Vertex on the "watch and wait" list, but that's it.

As I have discussed before, it's hard for me to get excited about the other Hep C players. Abbott(ABT) has a seemingly decent trio of drug candidates in later-stage development, but the impending spin off of AbbVie -- Abbott's pharma business -- makes the new company nearly completely dependent on the multi-blockbuster rheumatoid arthritis drug Humira.

Johnson & Johnson's(JNJ) TMC-435 looks solid but lacks an obvious companion unless the company partners with Gilead or physicians, on their own, decide to combine TMC-435 with Gilead's GS-7977 into an "off label" all-oral Hep C regimen -- an idea that BioMedTracker's Tucker believes is a real possibility. Finally, everyone wants me to like Achillion Pharmaceuticals, but there is no shortage of NS5A or protease inhibitors -- the company has two NS5As and a protease inhibitor -- so I can't get that excited.

Ironically given the longstanding investor skepticism, Gilead appears likely to dominate the Hep C market over the next decade. I still worry the company vastly overpaid for Pharmasset, but that concern will be meaningful only if something goes wrong and investors are looking for a cudgel with which to beat management. Otherwise, it's time for investors to start thinking logically about the real size of the Hep C treatment market. It's going to be hard for any company to make big money if there aren't enough Hep C patients to treat.

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

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

BMS and Tibotec team up HCV antivirals for phase II trial....

The HCV development partnership space is jumpin'! Medivir/Tibotec now has two partnerships, one with Gilead/Pharmasset in combination with their nuc PSI-7977 and now with BMS's daclatasvir. The question of what happens to the development of BMS's peg lambda is still a bit of a mystery.

December 02, 2011 07:30 AM Eastern Time

Bristol-Myers Squibb Enters Clinical Collaboration Agreement with Tibotec Pharmaceuticals for Phase II Combination Study in Patients Chronically Infected with Hepatitis C

NEW YORK--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that it has entered into a clinical collaboration agreement with Tibotec Pharmaceuticals, one of the Janssen Pharmaceutical Companies, to evaluate the utility of daclatasvir (BMS-790052), Bristol-Myers Squibb’s investigational NS5A replication complex inhibitor, in combination with Tibotec Pharmaceuticals' investigational NS3 protease inhibitor, TMC435, for the treatment of chronic hepatitis C virus (HCV).

Under the agreement the companies will evaluate the potential to achieve sustained viral response 12 and 24 weeks post treatment in patients with HCV genotype 1 in a study with three treatment regimens: an oral, once-daily treatment regimen of daclatasvir and TMC435 with pegylated-interferon alpha plus ribavirin; an oral, once-daily treatment regimen of daclatasvir and TMC435 with ribavirin and an oral, once-daily treatment regimen of daclatasvir and TMC435 alone. The study is planned to start in the first half of 2012.

“Bristol-Myers Squibb is dedicated to developing innovative treatment options for patients with serious diseases like HCV,” said Brian Daniels, senior vice president, Development. “We are pleased to work with Tibotec to advance the scientific understanding for the potential for an all-oral regimen of direct acting antivirals, which would be an important advancement for patients with HCV. This is a continuation of our leadership in forging partnerships to advance combination antiviral therapy.”

About daclatasvir (BMS-790052)

Discovered by Bristol-Myers Squibb through a genomics approach, daclatasvir is the first NS5A replication complex inhibitor to be investigated in clinical trials and is currently in Phase III development. Daclatasvir is part of a portfolio of investigational compounds that the company is developing for the treatment of hepatitis C.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward-Looking Statement

This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the compound described in this release will move from early stage development into full product development, that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or become a commercially successful product. Forward-looking statements in the press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2010, its Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

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jennifer.mauer@bms.com
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john.elicker@bms.com
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Teri Loxam, 609-252-3368
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PEG-Interferon Lambda shows higher RVR, less side-effects than Pegasys...

BMS is becoming a Hepatitis C antiviral powerhouse, showing some impressive data on their interferon-free NS5A inhibitor BMS-790052 and protease NS3 inhibitor BMS-650032 combo. They also are developing PEG-Interferon Lambda as part of their recent acquisition of ZymoGenetics. PEG-lambda achieved statistically significant (p<0.05) higher rates of cEVR (primary study endpoint) versus PEG-Interferon alfa at all doses [lambda 240 µg: 56.3% (n=103), lambda 180 µg: 55.9% (n=102), lambda 120 µg: 55.0% (n=100) vs. alfa: 37.9% (n=103)]. The two highest doses (240 µg and 180 µg) of PEG-lambda also displayed greater rates of RVR: 16.5% and 14.7% respectively vs 5.8% for PEG-alfa. In addition, there were fewer flu-like, musculoskeletal symptoms and cytopenia, as well as fewer interferon and ribavirin dose reductions for anemia in the PEG-Interferon lambda arms up to 12 weeks. However, rates of serious adverse events, depression and other common adverse events (incidence ≥10%) were similar across treatment arms up to week 12, which is a bit surprising. From my standpoint, any interferon that is even incrementally more efficacious and tolerable than what we currently have AND causes fewer dose reductions of the all-important ribavirin, would be a welcome alternative. - Chris


Written by TradersHuddle Staff
Saturday, 02 April 2011 11:33
PRINCETON, N.J.-( Business Wire )-

Bristol-Myers Squibb Company (NYSE: BMY) today announced results from the Phase IIb EMERGE clinical trial, in which treatment with the investigational compound PEG-Interferon lambda and ribavirin achieved higher rates of rapid virologic response (RVR) in genotypes 1, 2, 3, and 4, and complete early virologic response (cEVR) in genotypes 1 and 4 than the standard regimen of PEG-Interferon alfa and ribavirin in treatment-naïve patients chronically infected with hepatitis C (HCV). In this study, there were fewer flu-like and musculoskeletal symptoms and cytopenia, as well as fewer interferon and ribavirin dose reductions for anemia in the PEG-Interferon lambda arms up to 12 weeks. Rates of serious adverse events, depression and other common adverse events (incidence ≥10%) were similar across treatment arms up to week 12.

The EMERGE study findings were presented in a late-breaker oral session at the International Liver Congress (ILC), the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.

“There is a significant unmet medical need for more therapies that can benefit more hepatitis C patients. This is especially true for patients with HCV genotypes 1 and 4, who generally have lower response rates to treatment with PEG-Interferon alfa and ribavirin than patients with other genotypes,” said Stefan Zeuzem, MD, chief of the department of medicine and professor of medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany. “The EMERGE study results demonstrate that PEG-Interferon lambda may have the potential to help address this unmet need, and support further studies of this new type of investigational interferon.”

PEG-Interferon lambda is the first investigational type III interferon. Interferon lambda mediates antiviral activity through a receptor that is distinct from that used by interferon alfa and is present on fewer cell types within the tissues of the body. This restricted distribution of the interferon lambda receptor offers the potential for more targeted delivery of interferon therapy.

Study Results

Viral Response: HCV Genotypes 1 and 4

In this study, HCV genotype 1 and 4 patients treated with PEG-Interferon lambda achieved statistically significant (p<0.05) higher rates of cEVR (primary study endpoint) versus PEG-Interferon alfa at all doses [lambda 240 µg: 56.3% (n=103), lambda 180 µg: 55.9% (n=102), lambda 120 µg: 55.0% (n=100) vs. alfa: 37.9% (n=103)]. These statistically significant (p<0.05) higher viral response rates were seen as early as four weeks of treatment, with greater rates of RVR at the two higher doses of PEG-Interferon lambda (lambda 240 µg: 16.5%, lambda 180 µg: 14.7%, lambda 120µg: 6.0% vs. alfa: 5.8%). Viral Response: HCV Genotypes 2 and 3 In patients with HCV genotypes 2 and 3, treatment with all doses of PEG-Interferon lambda achieved cEVR rates similar to PEG-Interferon alfa [lambda 240 µg: 83.3% (n=30), lambda 180 µg: 96.6% (n=29), lambda 120 µg: 90% (n=30), and alfa: 86.2%, (n=29)]. Statistically significant (p<0.05) higher rates of RVR were achieved at the two higher doses of PEG-Interferon lambda (lambda 240 µg: 66.7%, lambda 180 µg: 75.9%, lambda 120 µg: 43.3% vs. alfa: 31%). Safety In this study, rates of adverse events commonly associated with interferon treatment were lower with PEG-Interferon lambda than with PEG-Interferon alfa. These adverse events included flu-like symptoms (lambda 240 µg: 9.7%; lambda 180 µg: 9.9%; lambda 120 µg: 12.5%; alfa: 42.9%), musculoskeletal symptoms (lambda 240 µg: 14.2%; lambda 180 µg: 14.5%; lambda 120 µg: 18.0%; alfa: 46.6%), neutropenia < 750/mm³ (lambda 240 µg: 0.0%; lambda 180 µg: 0.8%; lambda 120 µg: 0.0%; alfa: 15.2%), anemia with hemoglobin < 10 g/dL (lambda 240 µg: 12.9%; lambda 180 µg: 15.4%; lambda 120 µg: 20.5%; alfa: 43.9%.) and thrombocytopenia < 50K/mm³ (lambda 240 µg: 0.0%; lambda 180 µg: 0.0%; lambda 120 µg: 0.0%; alfa: 14.4%). The proportion of patients that required interferon dose reductions were: lambda 240 µg: 12.7%; lambda 180 µg: 3.8%; lambda 120 µg: 0.8%; alfa: 18.8%, and the proportion of patients that withheld and/or reduced ribavirin were: lambda 240 µg: 11.2%; lambda 180 µg: 4.6%; lambda 120 µg: 10.2%; alfa: 20.3%. The proportion of patients who required ribavirin dose reductions for anemia were: lambda 240 µg: 0.7%; lambda 180 µg: 1.5%; lambda 120 µg: 2.3%; alfa: 12.8%. Rates of serious adverse events, depression and other common adverse events (≥10%) were similar across treatment arms. Higher rates of elevated liver enzymes [AST or ALT >5x the upper limit of normal (ULN)] were seen in the highest-dose PEG-Interferon lambda treatment arm compared with PEG-Interferon alfa (lambda 240 µg: 17.4%; lambda 180 µg: 2.3%; lambda 120 µg: 0.8%; alfa: 7.6%), and direct bilirubin was also elevated (>1.2 mg/dL) in the highest-dose PEG-Interferon lambda treatment arm compared with PEG-Interferon alfa (lambda 240 µg: 7.6%; lambda 180 µg: 3.9%; lambda 120 µg: 0.8%; alfa: 0.8%); all resolved spontaneously without sequelae or following interferon dose modification and/or discontinuation.

About the EMERGE Phase IIb Study

The EMERGE study is a two-part, randomized, controlled, multicenter, phase II study of PEG-Interferon lambda in 526 treatment-naïve patients with chronic hepatitis C genotype 1, 2, 3 or 4. Part one of EMERGE was a Phase IIa study, and results were previously presented at The American Association for the Study of Liver Diseases (AASLD) 2010 Liver Meeting. Part two of EMERGE is an ongoing, blinded Phase IIb study designed to evaluate the safety, efficacy, and pharmacokinetics of PEG-Interferon lambda vs. PEG-Interferon alfa, both in combination with ribavirin. The 526 patients were randomized into four dose groups: PEG-Interferon lambda 240 µg (n=134), PEG-Interferon lambda 180 µg (n=131), PEG-Interferon lambda 120 µg (n=128) and PEG-Interferon alfa 180 µg (n=133).

The study will continue for 48 weeks in genotype 1 and 4 patients and 24 weeks in genotype 2 and 3 patients. The primary endpoint of the study is the proportion of patients who achieve complete early virologic response (cEVR).

About PEG-Interferon lambda

PEG-Interferon lambda is the first investigational type III interferon in Phase IIb development for the treatment of hepatitis C. Native human interferon lambda proteins are generated by the immune system in response to viral infection, and signal through a different receptor than native human interferon alfa proteins. Lambda receptors are present on fewer cell types within the human body than alfa receptors. This restricted distribution of the interferon lambda receptor offers the potential for more targeted delivery of interferon therapy.

About Hepatitis C1

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with blood. An estimated 170 million people worldwide are infected with hepatitis C. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, 20 percent will progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a curable disease.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the compound described in this release will move from exploratory development into full product development, that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q, and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

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* Rapid virologic response (RVR): undetectable viral load (HCV RNA <25 IU/mL) at week 4

† Complete early virologic response (cEVR): undetectable viral load at week 12


References

1 World Health Organization. Hepatitis C. Available at: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index1.html. Accessed March 9, 2011.

Bristol-Myers Squibb CompanyMedia:Cristi Barnett, 609-252-6028cristi.barnett@bms.comorInvestors:John Elicker, 609-252-4611john.elicker@bms.com