miR-122 inhibitor SPC3649 successfully inhibits HCV replication in chimps...

Posted 8/30/12 on Texas Biomed.org. Texas Biomedical Research Institute scientists in collaboration with Denmark's Santaris Pharma A/S have successfully inhibited HCV replication in chimpanzees using SPC3649, a DNA-based drug developed from Santaris's proprietary LNA ('Locked Nucleic Acid') technology. SPC3649 inhibits a host-based RNA molecule microRNA122 (miR-122) which HCV uses to replicate.  The drug is currently in phase II trials in humans and looks particularly compelling because of it's lack of any known side effects. 

Attacking the Silent Killer

Texas Biomed scientists have demonstrated that a new and novel class of drug targeting hepatitis C infections successfully inhibited replication of the virus in the liver of chimpanzees. The drug is now in phase two human clinical trials.

The drug was developed by the biopharmaceutical firm Santaris Pharma A/S in Denmark using its proprietary nucleic acid chemistry called “locked nucleic acid” or LNA. The drug, known as SPC3649, is a DNA-based drug that captures a small RNA molecule in the liver, called microRNA122 (miR-122) that is required for hepatitis C virus (HCV) replication.

“Our collaboration with Santaris Pharma proved that the drug worked exceptionally well in treating HCV infections in chimpanzees,” said Texas Biomed’s Robert E. Lanford, Ph.D., of the Department of Virology and Immunology. He was the lead author on the study appearing in the journal Science in January 2010.

One of the novel aspects of this drug is that it targets a host factor, miR-122, required by the virus, rather than directly targeting the virus itself. This helped prevent antiviral resistance, a major problem with therapies that directly target the virus.  Remarkably, this drug continued to work for several months after administration of the last dose.

The other novel aspect was the use of a DNA based therapy in what is called antisense technology. Antisense was supposed to be one of the “magic bullets” along with siRNA technology, but thus far no one has gotten them to work when systemically administered. Thus, this proof-of-concept study suggests that the LNA technology might also prove useful in using DNA based antisense drugs to treat many other diseases such as AIDS, cancer, and inflammatory diseases.

The study was conducted under a sponsored research grant to Texas Biomed. The primate studies were performed at Texas Biomed’s Southwest National Primate Research Center, which is supported by the National Institutes of Health.

HCV infections affect 170 million people worldwide and may progress over years to end-stage liver disease, including cirrhosis and liver cancer. In the United States, 4 percent of the adult population is chronically infected with HCV. The only U.S. FDA-approved therapy is pegylated-interferon and ribavirin, which is highly toxic, requires 48 weeks of treatment, and works in less than half of patients who are able to complete the full course of treatment. HCV infection is the leading reason for liver transplantation in the U.S, and HCV associated liver cancer is the most rapidly increasing cause of cancer death in the U.S.

Because it provides a high barrier to resistance, the new therapy could potentially replace interferon in future drug cocktails. “This antiviral could be used alone in long-term therapy to treat disease progression,” Lanford said. The new therapy may also be good to use after liver transplantation, because it may help suppress the replication of HCV in the new liver. The therapy has no known toxic or adverse reactions, and this is critical in the transplant setting.

In the study, four chimpanzees chronically infected with HCV were treated with the new antiviral drug. The two animals that received the higher dose had a reduction in virus levels in the blood and liver of approximately 350-fold. Additional surprising findings were the lack of antiviral resistant mutants and the fact that the therapy continued to work for several months after dosing stopped. An additional benefit of the drug was the reduction of total serum cholesterol by up to 45%, due to inhibition of the normal function of miR122 in cholesterol and fatty acid metabolism.

The new study was a critical proof of concept that the LNA technology could work for HCV. It proved that miR-122 is essential for HCV replication in an animal infected with HCV. Previously the role of miR-122 in HCV replication had only been shown in tissue culture. A second advance was the finding that LNA therapy could work against an important human disease in the chimpanzee model, suggesting that the new technology could be applied to other diseases.

Achillion Pharmaceuticals HCV pipeline suddenly looking attractive...

Posted 8/29/12 on Business Week.com. Achillion Pharmaceuticals, once regarded as an also ran by Big Pharma suddenly looks sexy again as clinical holds and pipeline failures stymie drug development with Idenix and BMS. Rumors of a takeover has made Achillion stock surge in the past couple of days. The HCV drug development space continues to be one of the most dynamic in pharma, there is definitely no shortage of spills and thrills. 

Achillion Deal Looming as Hepatitis Drugs Fail: Real M&A

By Ryan Flinn and Will Robinson on August 29, 2012

Achillion Pharmaceuticals Inc. (ACHN), the developer of hepatitis C treatments that was passed over by potential acquirers in the last year, is poised to draw renewed interest after setbacks by rival drugmakers.

Bristol-Myers Squibb Co. (BMY) last week said it was abandoning an experimental hepatitis C pill it obtained through its February purchase of Inhibitex Inc. after one patient died and others were hospitalized while taking the drug in a study. This week, Idenix Pharmaceuticals Inc. said U.S. regulators halted its study of a similar therapy, marking the second hold on clinical trials for the company this month.

With the market for new hepatitis C treatments projected to reach $20 billion by 2020 and Achillion facing no delays in two drugs under development, Piper Jaffray Cos. and William Blair & Co. say the $481 million company could gain fresh attention as a takeover candidate for Merck & Co. (MRK), Roche (ROG) Holding AG and Vertex Pharmaceuticals Inc. (VRTX) A suitor could pay a premium of as much as 79 percent to Achillion’s stock price and still acquire the New Haven, Connecticut-based company for less than its peak market value earlier this year, when takeovers and merger speculation spurred a surge in hepatitis C drugmakers’ shares.

“The frenzy has been taken out of the space, but I still think Achillion is very attractive” because its therapies have the potential to be the best of their type, Ted Tenthoff, a New York-based analyst for Piper Jaffray, said in a telephone interview. “We expect the wave of consolidation to continue. Achillion is clearly a target.”

Drug Development
Joe Truitt, Achillion’s chief commercial officer, said it wasn’t appropriate to comment on the company’s development plans, including the possibility of a takeover.

“We’ll make the best strategic options as they come to us, but for right now, we’re developing our drugs and getting them into combinations and making them available to patients,” Truitt said in a phone interview.

Today, shares of Achillion rose 3.5 percent to $6.86 at 9:45 a.m. in New York, the second-biggest gain among 116 stocks in the Nasdaq Biotechnology Index.

Hepatitis C is a viral infection that can cause liver damage and is estimated to affect 180 million people worldwide, according to the National Institutes of Health. Rising deaths among so-called baby boomers from the infection prompted U.S. health officials to declare in May that all of those born from 1946 to 1964 are at risk and should be tested.

Achillion is among several companies racing to develop hepatitis C cures that would replace the standard year-long injectable treatment that can cause flu-like symptoms.

Four Classes
There are four new classes of drugs under development to cure hepatitis C. Each work in different ways to stop the virus from replicating, and can be effective against one or several subtypes of the disease.

Drugmakers such as Abbott Laboratories (ABT), Achillion, Bristol- Myers, Gilead Sciences Inc. (GILD), Merck and Vertex have been testing these therapies, either alone or together, with varying degrees of success. The promise of a market that Achillion Chief Executive Officer Michael Kishbauch estimates will grow to $20 billion by 2020 spurred at least three acquisitions since October.

The biggest deal was Gilead’s $10.8 billion acquisition of Pharmasset Inc., announced in November, which came a month after Roche agreed to buy Anadys Pharmaceuticals Inc. for about $230 million. Bristol-Myers followed in January by announcing its $2.5 billion purchase of Inhibitex.

Fresh Look
Achillion’s Kishbauch said in November that the company was in “advanced discussions” with potential partners or acquirers. Its shares then reached a five-year high of $12.38 in February on takeover speculation before falling (ACHN) 46 percent since then as no deal materialized.

Now, with Bristol-Myers stopping development of the drug it bought from Inhibitex, and Idenix (IDIX) halting testing of a similar therapy, Achillion could attract a fresh look from companies seeking hepatitis treatments to use on their own or in combination with their existing therapies, said Liisa Bayko, a Chicago-based analyst with JMP Securities LLC.

Achillion is testing two types of drugs. By combining several classes of these new hepatitis C drugs, doctors may be able to limit the virus’ ability to infect, mimicking the strategy that a decade earlier helped turn HIV from a killer disease to a controlled one.

During the first quarter, Achillion will be reporting on how effective its two therapies work in combination. Good data could entice competitors to bid, Bayko said.

‘Well-Positioned’
“By the first quarter of next year, we could be a very different company,” Achillion’s Truitt said. “If that combination data comes through, then we really have a commercially viable, competitive combination that will put everybody on notice.”

“We’re pretty optimistic for Achillion,” Bayko said in a phone interview. “They’ll be well-positioned to be a candidate to be taken out, because right now, there are very few options if you want to get involved in hep C, in terms of combinations that are more advanced that are still in clinical development.”

Bayko said that while she expects a suitor to wait for the data on the drugs before making an offer, Achillion still could fetch as much as $10 a share if a company bid for it now, 51 percent more than its closing price yesterday.

Piper Jaffray’s Tenthoff said Achillion could lure suitors such as Merck, Roche and Vertex as they seek to compete against Gilead, which is seen by analysts as having the most promising hepatitis C drug. Gilead is poised to start testing two of its therapies together in a single pill this year, putting it on track to request U.S. regulatory approval for the drug in 2014.

Gilead Bid
Ronald Rogers, a spokesman for Merck, said the company doesn’t comment on speculation when asked whether the Whitehouse Station, New Jersey-based drugmaker was interested in Achillion, while an e-mail to Basel, Switzerland-based Roche’s media relations office wasn’t returned. Megan Pace, a spokeswoman for Cambridge, Massachusetts-based Vertex, declined to comment.

Even Gilead could seek to acquire Achillion as a way to remove a potential competitor and bolster its position, said Peter Kolchinsky, co-founder and general partner at RA Capital Management LLC, which oversees $300 million, including Achillion shares.

“Gilead could solidify its supremacy if it had Achillion’s drugs, each best in its respective class based on what we know so far,” Kolchinsky said in an interview. “Acquiring Achillion would also be a wise defensive move for Gilead, keeping it from falling into a competitor’s hands or from becoming an independent low-cost competitor.”

Safety Concerns
Cara Miller, a spokeswoman for Foster City, California- based Gilead, said the company (GILD) doesn’t comment on market speculation.

Brian Skorney, an analyst with Brean Murray Carret & Co. in New York, says Achillion won’t be a takeover target soon because it has “a lot more to prove” with clinical data next year. Other companies that developed hepatitis C treatments like Pharmasset and Inhibitex proved their drugs were effective before they were bought, and the only remaining question about their products was safety, he said.

The safety problems that challenged the drug Bristol-Myers bought from Inhibitex and the regulatory holds that Idenix faces show how much risk is still left in the market for hepatitis C treatments, said Les Funtleyder, a fund manager focused on the health-care industry at New York-based Poliwogg.

“What’s that phrase, ‘Once burned, twice shy?’” Funtleyder said in a phone call. “If someone was to repeat what happened to Bristol, shareholders would start to ask questions about management’s judgment.”

Cheaper Now
Still, after the drop in Achillion’s stock this year, a buyer would be taking on the risk of the therapies potentially failing at a lower price tag.

During the past 12 months, acquirers that announced deals for biomedical companies paid 65 percent more than the target’s average 20-day stock price in transactions greater than $500 million, according to data compiled by Bloomberg. A bidder for Achillion could offer a premium of as much 79 percent to yesterday’s stock price and still get the drugmaker for less than its record market value of $863 million in February.

The market for treating the viral infection is too big to be dominated by Gilead alone, so large drugmakers may have the appetite to acquire a company such as Idenix or Achillion once they produce sufficient data on the safety and effectiveness of their drugs, said Y. Katherine Xu, a New York-based analyst at William Blair. Kelly Barry, a spokeswoman for Cambridge, Massachusetts-based Idenix, didn’t return a voicemail message and e-mail sent after business hours about whether the company has been approached by suitors.

“Both Idenix and Achillion, their strategy is to sell themselves,” Xu said. “Timeline-wise, these two used to be similar, but now Achillion may be a little bit ahead.”

To contact the reporters on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net; Will Robinson in New York at wrobinson11@bloomberg.net.

To contact the editors responsible for this story: Sarah Rabil at srabil@bloomberg.net; Reg Gale at rgale5@bloomberg.net.

Idenix suffers another FDA-mandated clinical hold...

Posted 8/27/12 on Fierce Biotech.com. Idenix suffers another setback as the FDA puts its NS5B inhibitor, IDX19368 on clinical hold as the fallout from the AE's from BMS-094 continue. Both IDX184 and IDX19368 are in the same class of nucs as the ill-fated BMS-094 and share the same active metabolite. Idenix CEO Ron Renaud feels there is enough differentiation between BMS-094 and the Idenix compounds to put safety concerns to rest, but the company is doing its due diligence in terms of ensuring the safety of the patients enrolled in its trials. The clinical holds certainly slow down the development of Idenix's nucs, but hopefully Mr. Renaud is right and the Idenix compounds still hold market potential. 

Idenix plunges after FDA puts another hep C treatment on hold

August 27, 2012 | By John Carroll

Idenix already faces a partial clinical hold on its top hepatitis C program. Now the FDA has stepped in to add a clinical hold on its preclinical therapy IDX19368, another nucleotide polymerase inhibitor, or "nuc," in the pipeline. The biotech ($IDIX) also spelled out some added safety checks for its lead hep C treatment, which the company says can be completed in a matter of weeks. But its shares swiftly plunged on the fresh round of troubling news.

"Based on our discussions with the FDA, we understand the clinical hold is a precautionary decision made by the FDA in light of the adverse events seen with BMS-986094," said Idenix CEO Ron Renaud. "Both IDX184 and IDX19368 fall into the same broader class of NS5B inhibitors, and share the same active metabolite as BMS-986094. However, there are many attributes of our compounds, particularly the prodrug approach, that we believe favorably differentiate the toxicity profiles from that of BMS-986094."

Idenix's FDA woes were triggered by the abrupt failure of BMS-094, a once sizzling-hot hep C treatment which raised alarms after one patient died and 8 others in a study were hospitalized, just 8 months after Bristol-Myers Squibb paid $2.5 billion to acquire Inhibitex. Bristol ($BMY) announced on Thursday that it was writing off $1.8 billion and scrapping the drug entirely. Idenix added today that BMS is lending a hand in resolving the holds.

Idenix also reported that it has lined up ethocardiograms for 50 patients enrolled in its IDX184 study. A few done so far have not revealed any safety concerns and the developer says that it should be able to complete this process in a few weeks.

A lingering concern for Idenix, though, is whether the company can regain the glow that had enveloped it after some big deals in the hepatitis C space made the company a prime takeover target, with analysts speculating about the prospect for a big premium. The Cambridge, MA-based company has been among the leaders in the mad scramble to advance new "nucs" and NS5A inhibitors that can be combined with ribavirin into an all-oral regimen with megamarket potential.

Idenix shares plunged 40% on news of the partial hold 11 days ago. This morning the stock plunged another 16% in premarket trading. Both of these programs are unpartnered, which leaves Idenix holding the bag now for any long-term loss in value.

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

Subscribe to WSJ: http://online.wsj.com?mod=djnwires

Copyright © 2012 Dow Jones Newswires

CDC makes recommendation for HCV testing...

Posted 8/16/2012 on the CDC website. This new CDC recommendation that all of those born between 1945 and 1965 get tested for Hepatitis C is critical for HCV drug developers in that it will drive patients for the 2nd and 3rd wave of therapies currently in development. The recommendation is as important as the recommendation for colon cancer screening and, with proper mainstream media leverage, has the potential to drive patients into physician offices in similar volume. The upside is a potential second surge with current therapy and certainly immense anticipation for the simpler, more tolerable pan-genotypic 2nd and 3rd waves of HCV therapy currently in development. The potential downside is that the sheer number of patients may be the tipping point for an already overloaded and politically charged health care system short on resources.

CDC Now Recommends All Baby Boomers Receive One-Time Hepatitis C Test

New approach will help avert major increases in liver disease and deaths in the U.S.

All U.S. baby boomers should get a one-time test for the hepatitis C virus, according to final recommendations published today by the Centers for Disease Control and Prevention. One in 30 baby boomers – the generation born from 1945 through 1965 – has been infected with hepatitis C, and most don’t know it. Hepatitis C causes serious liver diseases, including liver cancer (the fastest-rising cause of cancer-related deaths) and is the leading cause of liver transplants in the United States.

The final recommendations are published in today’s issue of CDC’s Morbidity and Mortality Weekly Report. Draft recommendations were issued in May, followed by a public comment period.

“A one-time blood test for hepatitis C should be on every baby boomer’s medical checklist,” said CDC Director Thomas R. Frieden, M.D., M.P.H. “The new recommendations can protect the health of an entire generation of Americans and save thousands of lives.”

CDC’s previous recommendations called for testing only individuals with certain known risk factors for hepatitis C infection. Risk-based screening will continue to be important, but is not sufficient alone. More than 2 million U.S. baby boomers are infected with hepatitis C – accounting for more than 75 percent of all American adults living with the virus. Studies show that many baby boomers were infected with the virus decades ago, do not perceive themselves to be at risk, and have never been screened.

More than 15,000 Americans, most of them baby boomers, die each year from hepatitis C-related illness, such as cirrhosis and liver cancer, and deaths have been increasing steadily for over a decade and are projected to grow significantly in coming years.

CDC estimates one-time hepatitis C testing of baby boomers could identify more than 800,000 additional people with hepatitis C. And with newly available therapies that can cure up to 75 percent of infections, expanded testing – along with linkage to appropriate care and treatment – would prevent the costly consequences of liver cancer and other chronic liver diseases and save more than 120,000 lives.

Comments received from individuals and organizations during the public comment period (May 22-June 8, 2012) overwhelmingly supported CDC’s original proposal. As a result, the agency did not make substantive changes to the draft recommendations.

For additional information about hepatitis, visit www.cdc.gov/hepatitis.

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.

ImVacS 2012: Hepatitis C vaccine show promise

Press release posted 8/15/12 on Science Alert.com.au. Data presented on 8/13 at the Immunotherapies and Vaccine Summit (ImVacS) in Cambridge suggests a breakthrough in Hepatitis C vaccine research. Researchers took into account the highly error prone replication of HCV when creating this vaccine. By developing a vaccine that has only the most essential and highly conserved parts of the major viral surface protein, the body elicits antibodies that prevent both closely and distantly-related hepatitis C viruses from entering the cell and causing infection. Great promise involves great data however, of which we wait. 

Hep C vaccine breakthrough
 
WEDNESDAY, 15 AUGUST 2012

Hepatitis C affects around 200 million people around the world, and has a great ability to change its structure and evade the immune response, making it hard to vaccinate against. But the new vaccine candidate only contains the most essential, conserved parts of the viral surface protein, so it works on a variety of strains.

Currently undergoing formal preclinical studies, the vaccine is the result of breakthrough work done by Associate Professor Heidi Drummer with her team from the Institute’s Centre for Virology.

Hepatitis C affects around 200 million people around the world – a preventative vaccine has the potential to have a significant global health impact.

Associate Professor Drummer and her team have overcome a major hurdle in HCV vaccine research, developing a vaccine candidate that protects against a number of different HCV strains.

“Hepatitis C has a great ability to change its structure and evade the immune response. This makes vaccine development challenging,” Associate Professor Drummer said.

“Our vaccine is unique as it contains only the most essential, conserved parts of the major viral surface protein, eliciting antibodies that prevent both closely and distantly related hepatitis C viruses from entering cells, thereby preventing infection.”

Associate Professor Drummer unveiled the details about her HCV vaccine project at the prestigious Immunotherapeutics and Vaccine Summit (ImVacS) in Cambridge, Massachussets on August 13

Journal of Hepatology: "Myocardial injury in patients with chronic hepatitis C infection"

Abstract entitled "Myocardial injury in patients with chronic hepatitis C infection" posted online 8/13/12 in Journal of Hepatology.eu. A compelling study from Japan that definitely warrants further research into this phenomena and may add to the long list of extra-hepatic manifestations of having active, replicating Hepatitis C virus in the human body. This particular study found a link between myocardial perfusion and HCV.  Patients who achieved an SVR garnered better severity scores (SS) than prior to therapy. Relapsers saw improved SS scores while on therapy, but the scores worsened with the reappearance of virus.  If these results are confirmed, it adds to a growing base of evidence that dictates treating earlier instead of later. 

Article in Press

Myocardial injury in patients with chronic hepatitis C infection

Shigeo Maruyama, Masahiko Koda, Nobuyuki Oyake, Hidetoshi Sato, Yasuyoshi Fujii, Yutaka Horie, Yoshikazu Murawaki

Received 4 April 2012; received in revised form 13 July 2012; accepted 31 July 2012. published online 13 August 2012.

Accepted Manuscript

Abstract

Background & aims
The existence of a direct pathogenic link between hepatitis C virus (HCV) infection and myocardial injury has not been confirmed. We investigated the association between myocardial conditions and HCV in patients with HCV-related chronic hepatitis using thallium-201 myocardial scintigraphy.

Methods
In 217 consecutive cases of chronic HCV infection without overt heart disease, we performed electrocardiography (ECG), echocardiography, serum tests on myocardial injury and thallium-201 myocardial scintigraphy. Myocardial injury was confirmed by severity score (SS), which was calculated as the sum of thallium-201 perfusion defect scores. SS was followed prior to and after interferon (IFN) therapy in 200 patients with chronic hepatitis C.

Results
An abnormal ECG was found in 9% of the patients with chronic hepatitis C. Abnormal SS was found in 87% of chronic hepatitis C patients. Independent factors related to higher pretreatment SS were histology activity index score, serum HCV RNA titer and indocyanine green disappearance rate. After IFN therapy, SS was improved in patients with sustained virologic response. Among relapsers, the SS improved at the initial disappearance of HCV RNA, but SS worsened with reappearance of HCV RNA. The SS in non-viral responders did not change with IFN therapy.

Conclusions
Myocardial perfusion defects were found in 87% of the patients with chronic hepatitis C and improved with viral eradication from IFN therapy.

Medical Device industry makes a run at Pharma in the HCV space...

Posted 8/9/12 on The OTC Investor.com. Aethlon Medical is serious about it's Hemopurifier, a blood filtration device being looked at for several indications. If it is indeed capable of lowering HCV viral load to a point where pegylated interferon and ribavirin could be more effective and bump up response rates over 50% with less toxicity... and can do so at a cost lower than that of Direct Acting Antiviral combination therapy... Aethlon may be on to something. Yet another reason not to dismiss interferon just yet. 

Bristol’s Halted Hepatitis C Trial Reinforces Aethlon Medical’s Non-Toxic Therapy
By Paul Archie · Thursday, August 9th, 2012

In the biotechnology world, the sun rises and set around the two key words “safety” and “efficacy.”  A serious safety concern last week resulted in Bristol-Myers Squibb (NYSE: BMY) voluntarily halting its ongoing Phase 2 study of BMS-986094, a drug in development as a new indication for hepatitis C as part of the drug maker’s quest for an all-oral regimen for hep C.  A patient who had received a 200 milligram dose of the nucleotide polymerase inhibitor, or “nuke,” suffered heart failure; causing Bristol to stop the trial and begin evaluating participants to determine any correlation between the new drug and the heart damage.

In February, Bristol paid $2.5 billion to acquire Inhibitex, a 163-percent premium to the valuation of Inhibitex at that time, primarily to snag its hepatitis C drug candidate (then called INX-189).  The halted trial could seriously hamper Bristol in its race with Gilead (NASDAQ: GILD) and Abbott Labs (NYSE: ABT) to bring a new hepatitis C drug to market.  It is widely expected that an all-oral drug therapy for the liver disease that affects about 170 million people across the world will generate billions annually in sales.  It is the reason that Bristol paid the premium for Inhibitex and Gilead dished-out $11.1 billion last November to acquire Pharmassets and its hep C drug in development.

Investors that recognize the upside potential of new therapies for hepatitis C should be taking a close look at Aethlon Medical (OTCBB: AEMD), the maker of a first-in-class blood filtration device called the Hemopurifier®.  Recently released clinical research by Aethlon showed that the two most recent hepatitis C-infected patients to receive its Hemopurifier® therapy in combination with the standard of care peginterferon+ribavirin (PR) drug therapy achieved undetectable viral load at day-7.  In lay terms, that means that none of the hepatitis C virus was found in the patients’ bloodstream after seven days of treatment.

As an adjunct, the Aethlon Hemopurifier® selectively targets the rapid clearance of the hepatitis C virus from the entire circulatory system to improve benefit, dose, duration and tolerability of drug therapies.  Drugs, like that of Bristol, Gilead or Abbott, carry substantial safety risks because they are “additive” in nature, meaning that they are putting a foreign substance into the body.  Aethlon’s Hemopurifier® is “subtractive.”  It removes the virus through a proprietary filtering process, which does not carry the same, potentially deadly toxicity risks that can cost major pharma billions to finally realize.

The OTC Investor (http://s.tt/1kpgX)

'Viral Matters' HCV Drug Development discussion group on LinkedIn...

"Viral Matters" also has a home on LinkedIn as well, in the form of an HCV Drug Development discussion group. If you're a LinkedIn member, you can join the discussion here. 

Achillion releases mid-stage data on sovaprevir; advance NS5A inhibtior...

Press release posted 8/7/2012 on Equities.com. I always root hard for Achillion Pharmaceuticals, the scrappy underdog from Connecticut, so it's good to hear that their once-a-day PI sovaprevir is advancing nicely through the clinic coupled with the start of enrollment for phase 1 trials with their pan-genotypic NS5A inhibitor ACH-3102. Actually, given the recent, untimely demise regarding BMS' nuc BMS-094, it's good to hear about *anything* advancing in HCV drug development.  Hopefully Achillion will end up wagging their fingers in the faces of naysayers and develop a fully proprietary interferon-free anti-HCV combination. 

7:39 PM CDT, August 7, 2012


Achillion Announces Positive SVR4 Results From Phase 2 Study of Sovaprevir (Formerly ACH-1625) and Advancement of ACH-3102

Sovaprevir (formerly ACH-1625) achieves SVR4 of 85-100% of genotype 1 treatment naive patients treated with sovaprevir for 12 weeks followed by an additional 12 weeks of pegylated-interferon and ribavirin.

Enrollment of HCV-infected patients initiated in Phase 1 trial of ACH-3102, second generation pan-genotypic NS5A inhibitor

Conference call tomorrow August 8, 2012 at 10:00 a.m. EDT

NEW HAVEN, Conn., Aug. 7, 2012 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced sustained viral response (SVR4) results of 85 to 100 percent from an ongoing multi-dose Phase 2 trial evaluating 12 weeks of dosing with sovaprevir (formerly ACH-1625), a once-daily protease inhibitor, in combination with pegylated interferon plus ribavirin (P/R) followed by an additional 12 weeks of P/R. In addition, the Company announced today that ACH-3102, a second-generation pan-genotypic NS5A inhibitor, has been safe and well tolerated by healthy volunteers in both single and 14-day multiple ascending dose groups. Further, enrollment of patients in a Phase 1 proof-of-concept clinical trial to evaluate the safety and efficacy of ACH-3102 in patients with genotype 1 HCV has been initiated.

"We are very pleased to reach these important milestones in our HCV portfolio including positive SVR4 results with sovaprevir and the advancement of ACH-3102, our second-generation pan-genotypic NS5A inhibitor, through Phase 1 dose-escalation," commented Milind S. Deshpande, Ph.D., President of Research and Development and Chief Scientific Officer. "The safety and efficacy seen with sovaprevir across dose groups provides us with confidence that this next-generation protease inhibitor will play an important role in an all-oral treatment for HCV. The safety and tolerability seen to date with ACH-3102, for which we expect to report proof-of-concept next month, combined with the compound's in vitro profile, lead us to we believe we have an in-house portfolio of optimized compounds that can successfully create an all-oral, interferon-free regimen for the treatment of genotype 1 HCV. We look forward to beginning combination studies with sovaprevir and ACH-3102 by the end of the year."

Sovaprevir: Updated Phase 2 results including SVR4
In June 2011, Achillion initiated a randomized Phase 2 trial evaluating three doses (200 mg, 400 mg, or 800 mg) of sovaprevir given once daily in combination with pegylated interferon plus ribavirin (P/R) for 12 weeks followed by an additional 12 or 36 weeks of P/R, for the treatment of genotype 1 HCV.

As previously reported in April 2012, of the 58 patients enrolled in this study, the majority had HCV genotype 1a (n=35 (60%)), with remaining patients having HCV genotype 1b (n=20) or genotype 1 (n=3). Approximately 71% of the patients were IL28B genotype CT/TT, the more difficult to treat mutation, 64% were male and 17% were African American. The complete early virologic responses (cEVR) across the 200 mg, 400 mg, and 800 mg sovaprevir dose groups were 100%, 94% and 100%, respectively.

Today, the Company reported SVR4 rates of 90%; 85%; and 100% in the 200 mg, 400 mg, and 800 mg dose groups, respectively, after 24 weeks of therapy consisting of 12 weeks of sovaprevir and P/R followed by additional 12 weeks of P/R. In all, 39 patients were assigned to receive an additional 12 weeks of P/R therapy with the remaining 14 patients assigned to receive an additional 36 weeks of P/R.

    Sovaprevir (ACH-1625) Virologic End Point 200 mg 400 mg 800 mg   n=19 n=20 n=19 RVR       (HCV RNA < 25IU/mL week 4) 79% (15/19) 89% (16/18)  90% (17/19) cEVR       (undetectable at week 12) 100% (18/18) + 94% (15/16) ++ 100% (19/19) Patients assigned to 12 weeks of sovaprevir and P/R followed by 12 weeks of P/R through week 12 12 13 14 Undetectable at end of treatment 100% (10/10) * 92% (12/13)  100% (14/14) SVR4       (undetectable at week 28) 90% (9/10) 85% (11/13) 100% (13/13)** + One patient withdrew for AE deemed unrelated to sovaprevir. ++ One patient withdrew consent, one patient moved, both undetectable at the time of withdrawal; two patients withdrew for AEs deemed unrelated to sovaprevir. * Two patients lost to follow-up, both undetectable at last assessment. ** One patient lost to follow up, undetectable at last assessment.

As previously reported, sovaprevir was generally well tolerated across all dose groups. Adverse events (AEs) in patients receiving sovaprevir were classified as mild to moderate and were transient. The most common AEs were consistent with P/R treatment.

Additional clinical trial results, including SVR4 and SVR12 for all patients treated with sovaprevir followed by an additional 12 weeks or 36 weeks of P/R, are expected be reported during the first quarter of 2013.

ACH-3102: Phase 1 trial in Healthy Volunteers and HCV-infected patients
In May 2012, Achillion initiated a Phase 1 clinical trial evaluating the safety and tolerability of single and multiple ascending doses of ACH-3102, a once daily, second-generation, pan-genotypic NS5A inhibitor, in healthy volunteers.

To date, 42 healthy volunteers have received a single dose of ACH-3102, ranging from 25 mg to 1,000 mg. An additional 24 healthy volunteers have received 14 days of once daily ACH-3102, with doses ranging from 25 mg to 75 mg. Preliminary data from both the single and multiple ascending dose groups demonstrated that ACH-3102 was well tolerated at all doses evaluated. There were no serious adverse events, no clinically significant changes in vital signs, electrocardiograms (ECGs), or laboratory evaluations. All reported adverse events were classified as mild or moderate, and were transient in nature.

Achillion announced today the initiation of enrollment of patients with genotype 1 HCV into a Phase 1 study to evaluate the safety, tolerability and antiviral activity of ACH-3102. The trial will initially evaluate the safety and antiviral activity of a single dose of ACH-3102. Initial results are expected to be reported during the third quarter of 2012.

Conference Call
Achillion will host a conference call and simultaneous webcast on Wednesday, August 8, 2012 at 10:00 a.m. EDT. To participate in the conference call, please dial (877) 266-0482 in the U.S. or (631) 291-4565 for international callers. The conference call ID is 13643523. A live audio webcast of the call will be accessible at www.achillion.com, under the News Center section of the website. Please connect to Achillion's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.
A replay of the webcast will be available on www.achillion.com. Alternatively, a replay of the conference call will be available starting at 1:00 p.m. EDT on August 8, 2012, through 11:59 p.m. Eastern time on August 15, 2012 by dialing (800) 585-8367 or (404) 537-3406. The replay passcode is 13643523.
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 safety, efficacy and potential benefits of sovaprevir, expectations about milestone achievement including the potential to achieve proof-of-concept for ACH-3102 and initiation of all-oral, interferon-free clinical trials evaluating regimens containing sovaprevir (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 its drug candidates, including 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.

CONTACT: Company Contact: Glenn Schulman Achillion Pharmaceuticals, Inc. Tel. (203) 624-7000 gschulman@achillion.com Media: Christin Culotta Miller Ogilvy PR Tel. (646) 229-5178 christin.miller@ogilvypr.com Investors: Mary Kay Fenton Achillion Pharmaceuticals, Inc. Tel. (203) 624-7000 mfenton@achillion.com Investors: Seth Lewis The Trout Group, LLC Tel. (646) 378-2952 slewis@troutgroup.com Source: Achillion Pharmaceuticals, Inc.

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.

BMS halts development of Phase 1 anti-HCV nuc, BMS-986094...

Posted 8/2/12 on MedPage Today.com. BMS halts development of its investigational nuc BMS-986094 for treatment of chronic HCV after one of the patients the 200mg arm of the  phase 1 trial suffered heart failure. It is unknown at time of publishing whether the drug was directly linked to the drug and all patients involved with the trial are undergoing full assessment.  This effectively makes GS-7977, Gilead's nucleotide analog one of the only nucs currently in advanced development unscathed by toxicity and certainly adds to it's luster, at least in the short term. 

Safety Issue Halts Study of BMS HCV Drug

By Michael Smith, North American Correspondent, MedPage Today
Published: August 02, 2012

Bristol-Myers Squibb has suspended treatment "to protect patient safety" in a phase IIb trial of an investigational oral drug for hepatitis C.

A spokeswoman for the company said the decision was made after one of the patients getting 200 mg of the compound, dubbed BMS-986094, suffered heart failure.

Bristol-Myers Squibb is not giving further details on the patient's condition, according to Cristi Barnett, the company's associate director of public affairs.

In an email to MedPage Today, Barnett said it's still not clear what caused the heart failure or whether it's related to the study drug. To try to clarify the issue, BMS is doing "an immediate assessment of all patients receiving 094 at any dose," Barnett said.

"This assessment includes full physical exams and histories, and cardio ECHO imaging and ECGs for all patients," Barnett said. "Any clinically significant cardiac ECHO abnormality will then be reviewed by a consulting cardiologist as soon as possible."

The drug is a nucleotide NS5B polymerase inhibitor and was acquired by the company when it paid $2.5 billion in January to purchase Inhibitex, the original developer. It was first known as INX-08189.

It's one of several under development -- both Gilead Sciences of Foster City, Calif., and Vertex Pharmaceuticals of Cambridge, Mass., have competitors in the field.

The range of potential treatments for the virus, blamed for about 15,000 deaths annually in the U.S., has been expanding dramatically with the recent development of so-called direct-acting agents.

Two HCV protease inhibitors -- telaprevir (Incivek) and boceprevir (Victrelis) -- are already on the market, but they are indicated for use with pegylated interferon-alfa and ribavirin, which aim at stimulating the immune system rather than targeting the virus directly.

The goal has been to develop all-oral combinations of direct-acting agents that would eliminate the need to use interferon and ribavirin.

BMS-986094 was being tested in a two-part dose-ranging study, dubbed AI472-003, among patients with HCV genotypes 2 or 3 who had not been previously treated. Genotypes 2 and 3 are regarded as being easier to cure than genotype 1.

The first part of the 12-week study was double-blinded and included 90 patients in four treatment arms. In the comparator arm, patients were treated with pegylated interferon-alfa and ribavirin, plus an oral placebo.

In the remaining arms, patients got interferon and ribavirin plus 25, 50, or 100 mg of BMS-986094.

The second part of the study, planned to include 120 patients, was open label for 12 weeks and had five arms.

In two arms, patients took either 100 or 200 mg of BMS-986094, combined with ribavirin. In two others, they took the same doses of the drug, this time combined with daclatasvir, the company's investigational NS5A replication complex inhibitor.

Finally, in the fifth arm, they took 50 mg of BMS-986094 and both daclatasvir and ribavirin.

Novartis restructures HCV licensing deal with Idenix...

Posted on 8/1/2012 on PharmaTimes.com. It seems like subtle change is afoot in the HCV drug development field. Gilead announced that it would co-formulate GS-5855 and GS-7977 into one pill with an expected launch date of 2014 and Vertex posted earnings well below expectations of Wall Street on lower-than-anticipated sales of Incivek. Now, Novartis announces it is restructuring it's licensing deal with Idenix, giving the latter company back it's development rights for it's HCV pipeline. We can only speculate on why the rights were handed back to Idenix, but I'm sure Gilead's bold announcement and the post-EASL dampening of the current marketplace and it's chilling effect on the life cycles of the first generation of anti-HCV drugs didn't offer any remedy for cold feet.


Idenix gets rights back to pipeline from Novartis
WORLD NEWS | AUGUST 01, 2012

KEVIN GROGAN

Idenix Pharmaceuticals has regained the rights to hepatitis C compounds that were partnered with Novartis and announced plans to raise $150 million.

The US firm and the Swiss major first teamed up in May 2003 when the latter purchased a 54% stake in Idenix and licensed the hepatitis B treatment Tyzeka/Sebivo (telbivudine). Under the original agreement, Novartis had the option to license any of Idenix' candidates after proof-of-concept, so long as it maintained at least a 30% stake.

Novartis currently has a 31% holding but the pact has now been restructured. The option to license Idenix's development-stage drug candidates in any therapeutic area has been terminated and Novartis will be entitled to royalties on future hepatitis C virus drugs.

Novartis will have a non-exclusive option to conduct trials evaluating a combination of any of its and Idenix' HCV drug candidates, and the latter firm will no longer receive royalty or milestone payments from Tyzeka/Sebivo sales. The Basel-headquartered group will retain the right to designate one member to Idenix's board, reduced from two, as long as it continues to own at least a 15% stake.

Ron Renaud, Idenix chief executive, said the new agreement gives the firm "increased flexibility to optimise the value of our pipeline". By regaining the worldwide rights to all its drug candidates, "we believe Idenix will be well-positioned to develop pan-genotypic all-oral direct-acting antiviral combination treatments with potential collaborators," he added.

As the restructured deal was being announced, Idenix noted that it has commenced an underwritten registered public offering of $150 million of its common stock.

The proceeds will be used to develop combination Phase IIb trials of its HCV drugs IDX184 and IDX719, and Phase IIa studies with IDX19368 in combination with ribavirin. The funds may also be used to "potential acquisitions of new businesses, technologies or products that Idenix believes complements or expands its business".