Australia's Benitec Biopharma to purchase Tacere Therapeutics and it's new HCV drug...

Posted 10-11-2012 on www.LifeScience.com.au. Australia's Benitec Biopharma is set to purchase San Jose, CA - based Tacere Therapeutics. Tacere is currently in phase I/II trails with TT-034, an anti-HCV compound developed using Benitec's ddRNAi (DNA-directed RNA interference) technology. TT-034 has been described as a 'cocktail in one drug', containing three seperate RNAi elements targeted against the Hepatitis C virus. The drug is encapsidated in an adeno-associated virus (AAV) protein coat. The drug has so far been shown to safely penetrate hepatocytes - in preclinical animal studies, TT-034 monotherapy targeted and cleaved the Hepatitis C virus itself at the different sites simultaneously without toxicity.

Benitec to buy Tacere and its new hepatitis C treatment drug

Benitec Biopharma (ASX:BLT) will acquire Tacere Therapeutics, which has a phase I/II ready hepatitis C treatment candidate developed using Benitec's ddRNAi technology.

Dylan Bushell-Embling (Australian Life Scientist)11 October, 2012 14

Benitec Biopharma (ASX:BLT) has arranged to acquire US-based Tacere Therapeutics, and its phase I/II ready hepatitis C treatment candidate.

The financial terms of the acquisition include the allocation of just over $1.5 million in new Benitec shares – or around 9.5% of issued share capital – and an agreement to split future potential licensing revenue.

The size of Tacere's cut of this revenue will be between 2.5% and 35% depending on the stage of the product's commercial development at the time a licensing deal is entered into.

For example, if a licensing deal emerges prior to the commencement of phase II trials, the cut will be 35%. But if an agreement does not come until after Biologic License Application is filed with the US Food and Drug Administration, this falls to 2.5%.

Tacere's hepatitis C treatment candidate is the compound TT-034. The program is based on gene-silencing technology owned by Benitec known as DNA-directed RNA interference, or ddRNAi. This technology was originally developed by the CSIRO then exclusively licensed to Benitec.

Benitec CEO Dr Peter French said he expects the acquisition to bring substantial benefits for the company.

“Tacere has been successfully developing programs utilising Benitec's proprietary ddRNAi technology since 2006, and it now makes sense to bring these assets in-house to complement and strengthen our pipeline as we move into clinical development,” he said.

"We believe the preclinical data and safety profile of TT-034 [also] positions the Company to commence clinical trials in hepatitis C at a time when a number of high profile HCV therapies such as nucleotide polymerase inhibitor are encountering safety concerns.”

Tacere, which licenses ddRNAi technology for its hepatitis C program, has been developing the treatment candidate for years.

In 2008, the company entered into a collaboration and licensing arrangement with Pfizer for the program. Pfizer invested in TT-034 development until 2011, when it shut down the UK facility where it was conducting the program during a restructuring. The rights then reverted back to Tacere.

Benitec (ASX:BLT) shares were trading 7.14% higher at $0.015 as of 2:30pm on Thursday.

Medivir moves to strengthen its HCV portfolio...

Press release dated 9-5-12 on the Medivir AB website. Medivir bolstered it's HCV portfolio by purchasing anti-HCV related preclinical research compounds from Novadex Pharmaceuticals. This purchase includes IP and prodrug technologies as well in hopes that it could be applied to both HCV protease inhibtors and nucleoside analogs to give a boost to the pharmacokinetic properties. Medivir already has TMC-435 in collaborative development with Janssen Pharaceuticals, now in Phase III clinical trials. 

Medivir acquires preclinical antiviral programs including hepatitis C and prodrug technologies

05-Sep-12 Stockholm, Sweden—Medivir AB (OMX: MVIR), announced today that it has acquired preclinical research stage assets from Novadex Pharmaceuticals AB. The acquisition includes intellectual property and prodrug technologies in order to further strengthen Medivir’s hepatitis C platform and know how.

The acquired portfolio of research stage antiviral programs includes novel nucleotide polymerase inhibitors that have been identified and developed. It also includes prodrug technologies which could be applied to both protease inhibitors and nucleoside analogues to enhance their overall pharmacokinetic properties.

“We are very pleased to be able to make these additions to the Medivir R&D portfolio, which will further strengthen our pipeline and capabilities in the antiviral disease area. There are several synergies with the Medivir anti-viral projects and prodrug approaches which we aim to explore” comments Charlotte Edenius, Medivir’s EVP of Research and Development

The transaction value, which consists of up-front payment as well as future potential milestone payments, is not disclosed.

For more information about Medivir, please contact:

Medivir Direct: +46 8 440 6550 or:
Rein Piir, EVP Corporate Mobile: +46 708 537 292
Affairs & IR
M:Communications medivir@mcomgroup.com
Europe: Mary-Jane Elliott, +44(0)20 7920 2330
Amber Bielecka, Hollie Vile

About Medivir

Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir (TMC435), a novel protease inhibitor in phase III clinical development for hepatitis C that is being developed in collaboration with Janssen Pharmaceuticals.

In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia. and today Medivir has a broad product portfolio with prescription pharmaceuticals in the Nordics.

Medivir’s first product, the unique cold sore product Xerese®/Xerclear®, is launched in collaboration with GlaxoSmithKline to be sold OTC under the brand name ZoviDuo in Europe, Japan and Russia.

Medivir’s IPO was in 1996 and currently the company has around 180 employees.

For more information about Medivir, please visit the Company’s website: www.medivir.com

Investing Daily.com: Hepatitis C Drug Companies and All-Oral Treatment - A $20 Billion Market

Posted 8/28/12 on Investing Daily.com. Author and investor Jim Finks takes a look at the current HCV Drug Development space. Of note is the projected $20 billion worldwide HCV drug market which he feels will greatly be increased from the current $5 billion if drugs with better tolerability and efficacy make it to market, coupled with the benefit of interferon-free regimens for some patients.    

Hepatitis C Drug Companies and All-Oral Treatment: A $20 Billion Market

by JIM FINK on AUGUST 28, 2012
in STOCKS TO WATCH

Last week I wrote about 3 Stock Plungers and only liked the future prospects of one of the stocks: Idenix Pharmaceuticals (NasdaqGM: IDIX). My main reason for thinking a sustainable stock rebound is possible was because it’s a top-ten holding of value-investing legend Seth Klarman, who owns a 9.2% stake in the company (10 million shares) at an average purchase price of $8 per share (30% higher than the stock’s current price of $6.15). Klarman’s Baupost Group has bought shares in Idenix for five consecutive quarters.

This begged the question why Klarman is so enamored with Idenix. I couldn’t get an interview with Klarman to ask him and Baupost Group’s 2011 shareholder letter (dated Jan. 31, 2012) doesn’t mention Idenix — even though Klarman started buying the stock in Q2 2011. Consequently, I needed to research Idenix myself.

Hepatitis C Virus is a Global Killer
I discovered that the Idenix investment story is all about the market opportunity for treating Hepatitis C, a virus that infects the liver and is life-threatening – slowly destroying the liver over 20-30 years (resulting in cirrhosis or cancer). For those that are unsure, the liver is a vital organ that we cannot live without.

There is no vaccine for Hepatitis C, so the number of people who will get infected (e.g., sexual intercourse, tattoos, blood transfusions/dialysis, sharing dirty needles, mother/child) is predictable and not likely to go down. Furthermore, the body does not develop immunity from experiencing the disease, so people can get infected multiple times. In other words, the market demand for Hepatitis C drug cures is high and long-lasting. Below are some facts about Hepatitis C:

Worldwide, 180 million people are infected and 350,000 die each year.
In the U.S., 3.2 million people are infected, between 32,000 and 110,000 are newly infected each year, and 15,000 to 20,000 die each year.
75% of infections are curable, but up to 75% of all infected people don’t realize that they have the disease because they don’t look or feel sick – until it is too late.

Annual global sales of Hepatitis C drugs is currently $5 billion, but analysts project that new drug treatments with fewer side effects and oral application could generate a worldwide market opportunity of $20 billion.

The U.S. Centers for Disease Control and Prevention (CDC) recently recommended that all baby boomers born between 1946 and 1964 (76 million people aged 47 to 67) be tested for Hepatitis C infection.

Treating Hepatitis C with Interferon Injections is Unpleasant
Prior to 2011, the standard treatment for Hepatitis C was a combination of immune-boosting peginterferon injections – offered by Merck (NYSE: MRK) and Roche Holding AG (OTC Markets: RHHBY) — and ribavirin anti-viral pills (ribavirin patent has expired, so generic versions are available from several companies). Course of treatment was long at 48 weeks and costs $15,000 to $30,000, the cure rate was only 46% and there were severe side effects (e.g., flu-like symptoms, anemia, depression).

Treating Hepatitis C with Protease Inhibitors Is Better But Still Requires Interferon
Then, in May 2011, the Food & Drug Administration (FDA) approved two new Hepatitis C drugs called “protease inhibitors” that promise much higher cure rates (75%) and shorter treatment protocols (half as long at 24 weeks). Both of these drugs are taken orally in pill form but only work in conjunction with the standard peginterferon injections and ribavirin treatment. The two new drugs are:

Victrelis by Merck, which has a 66% cure rate, costs between $26,400 and $48,400 per course of treatment, and requires 12 pills per day.

Incivek by Vertex Pharmaceuticals (NasdaqGS: VRTX), which has a 79% cure rate, costs $49,200 per course of treatment, and requires 6 pills per day.

Based on the higher cure rate and simpler dosing from Incivek, it should come as no surprise that Incivek is outselling Victrelis 3-to-1.

Treating Hepatitis C with All-Oral Nucleotide Drugs is the Holy Grail

But Vertex’s dominance with Incivek could be short-lived because other drug companies are working on new Hepatitis C drugs called “nucleotides” that offer the holy grail of therapy: pill-only treatment that does not require the peginterferon/ribavirin injection albatross.

Perhaps in the forefront of all-oral Hepatitis C treatment is Gilead Sciences (NasdaqGS: GILD), which in November 2011 acquired biotech company Pharmhasset in a monstrous $10.8 billion all-cash deal. Pharmhasset’s Hepatitis C drug in Phase III trials is called PSI-7977 and could be on the market by 2014. According to Gilead, PSI-7977 is “way ahead of everybody else” and promises a cure in only 8-to-12 weeks of treatment. However, news in February that patients experience a relapse of Hepatitis C symptoms after stopping treatment with PSI-7977 caused Gilead’s stock price to suffer its largest one-day drop in 11 years. Since February, Gilead has recovered to all-time highs, which suggests investors have concluded that PSI-7977 will remain the core treatment for Hepatitis C – perhaps in combination with other drugs — despite the relapse issue.

Gilead’s drug may be best, but it won’t be the first all-oral treatment on the market because Roche Holdings is expected to offer an all-oral drug cocktail possibly consisting of setrobuvir (obtained in its acquisition of Anadys Pharmaceuticals in October 2011), danoprevir (purchased from InterMune (NasdaqGS: ITMN) in October 2010), and Merck’s Victrelis.

With Bristol-Myers Squibb’s (NYSE: BMY) abandonment of the Hepatitis C drug (BMS-986094) acquired from Inhibitex for $2.5 billion and the FDA clinical hold on Idenix’s Hepatitis C drug (IDX-19368) pending additional safety data, the path to riches in Hepatitis C treatment is proving to be a tortuous one. Other drug companies in the race for Hepatitis C drug treatments or vaccines include:

Achillion Pharmaceuticals (NasdaqGS: ACHN)
Abbott Laboratories (NYSE: ABT)
Dynavax Technologies (NasdaqCM: DVAX)
Peregrine Pharmaceuticals (NasdaqCM: PPHM)
Inovio Pharmaceuticals (NYSE: INO)
Medivir AB (OTC Markets: MVRBF) –  in partnership with Johnson & Johnson (NYSE: JNJ)

Achillion is a Prime Takeover Candidate
Of all of these companies, the best speculative buy right now may be Achillion. It is a pure-play on Hepatitis C with two promising drugs under development (one protease inhibitor and one NS5). There are no FDA clinical holds on Achillion’s drug pipeline like there are on Idenix and Achillion’s small market cap of $481 million makes the company an easily digestible acquisition for big boys like Gilead, Roche, Merck, or Abbott.

Furthermore, I have a soft spot for Achillion because it is located in New Haven, Connecticut (where I lived for four years) and is in partnership with my alma mater, Yale University. Good things happen to people and companies associated with a top-notch educational institution like Yale.

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.

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

'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 discloses additional data on HCV protease inhibitor ACH-2684

Posted on 5/21/12 via MarketWatch.com. Look what happens when I go away for a week. The CDC changes it's guidelines to include one-time HCV testing for Baby Boomers (FYI, HCV drug developers had a hand in shaping this shift in public policy via the Viral Hepatitis Action Coalition for all you fans of government-corporate relationships) and Achillion continues to shore up their pipeline with decent drugs. OK, so a 3.73 log10 drop isn't exactly Telaprevir-like, but given the right backbone regimen - hopefully one also developed and manufactured by this currently unpartnered company - Achillion could hit it big. 

Achillion Announces Additional Proof-of-Concept Data With ACH-2684 for the Treatment of Hepatitis C

Achieves Up to 3.73 log10 Reduction in Genotype 1 HCV RNA After Three Days of Treatment With Once-Daily 400 mg ACH-2684 in Phase 1b Study

NEW HAVEN, Conn., May 21, 2012 (GlobeNewswire via COMTEX) -- Achillion Pharmaceuticals, Inc. ACHN +10.92% today reported proof-of-concept data from a Phase 1b clinical trial demonstrating that patients with chronic hepatitis C (HCV) genotype 1 (GT 1) treated with ACH-2684, a second-generation protease inhibitor, achieved a mean maximum 3.73 log10 reduction in HCV RNA after three-day 400 mg monotherapy with once-daily (QD) dosing. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with HCV.

"We believe ACH-2684, with its potent antiviral activity achieved without boosting and once-daily dosing, is one of the most intriguing protease inhibitors in clinical development for the treatment of HCV," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "As we continue to focus our efforts on advancing our internally developed all-oral, interferon-free HCV regimen consisting of ACH-1625, our next generation protease inhibitor, in combination with ACH-3102, a second generation pan-genotypic NS5A inhibitor, we believe that the profile of ACH-2684 provides a significant strategic and therapeutic option for potential combinations with either ACH-3102 or other direct-acting antiviral agents."

ACH-2684 Phase 1 Clinical Trial

Achillion is evaluating ACH-2684 in a Phase 1 randomized, double-blind, placebo-controlled clinical trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity in healthy subjects and HCV-infected patients. The trial consists of three segments: Phase 1a assessment of single ascending oral doses (SAD) in healthy volunteers, Phase 1a 14-day multiple ascending doses segment (MAD) in healthy volunteers, and Phase 1b evaluation of three days of oral repeat doses in subjects with GT 1 or 3 HCV. The MAD segment of this trial will be initiated during the second quarter and full trial results are expected to be presented at a medical meeting in the fourth quarter of 2012.

During the oral repeat doses segment in subjects infected with GT 1 HCV, a total of 30 patients were enrolled including 6 patients receiving placebo and 24 patients treated with three doses of 100 mg once daily (n=8), 400 mg once daily (n=8), or 400 mg twice daily (n=8) of ACH-2684. No serious adverse events (SAE) were reported and there were no patient discontinuations during treatment. The mean maximum GT 1 HCV RNA decline during therapy for the 100 mg QD, 400 mg QD, and 400 mg BID groups were 3.36 log10, 3.73 log10, and 4.16 log10, respectively, compared to a 0.68 log10 decline for patients receiving placebo. There were no viral breakthroughs observed during ACH-2684 monotherapy. Additional assessments of GT 3 activity are currently under development.

Safety data from the SAD and HCV-infected segments of the trial demonstrated ACH-2684 was well tolerated at all doses evaluated up to and including the maximum total daily dose of 1400 mg. 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. Dosing in the 14-day MAD segment is being initiated during the second quarter with longer term safety data expected to be available in the third quarter of 2012.

About ACH-2684

ACH-2684 is a next-generation HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-2684 is a macro-cyclic, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-2684 demonstrated pico-molar potency, excellent pharmacokinetic properties and safety profile at high drug exposures. ACH-2684 also exhibits rapid and extensive partitioning to the liver, as well as high liver/plasma ratios in preclinical studies. ACH-2684 has shown pico-molar potency against NS3 protease that is specific to HCV. It has preclinical activity against the 6 known genotypes of HCV and exhibits equipotent activity against HCV genotypes 1a and 1b at an IC50 of approximately 100 pico-molar. The drug candidate was discovered internally and is being advanced by Achillion.

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 potency, safety, tolerability, effectiveness and other characteristics of Achillion's ACH-2684, ACH-1625 and ACH-3102; Achillion's expectations regarding timing for the commencement, completion and reporting of results of clinical trials of drug candidates including ACH-2684, ACH-1625 and ACH-3102; and Achillion's ability to advance a potentially best-in-class all-oral, interferon-free combination of ACH-1625 and ACH-3102 and ACH-2684 in combination with ACH-3102 or other direct acting antiviral agents. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage nonclinical studies and clinical trials of ACH-2684, ACH-1625 and ACH-3102; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and its subsequent SEC filings.

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

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

SOURCE: Achillion Pharmaceuticals, Inc.



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

BMS Phase II DAA-only Proof of Principle regimen published in the New England Journal Of Medicine...

Apologies for the lack of activity, just back from a great, relaxing vacation in Kauai. Once the plane landed at LAX, I was immediately stressed-out again. It's amazing how fast the return to status quo occurs post-vacation. 


On to the big news regarding the synergistic combination of BMS's investigational NS5A inhibitor, Daclatasvir and NS3 protease inhibitor, Asunaprevir both with and without the addition of pegylated interferon and ribavirin. This is old news by now to the HCV infomaniacs who frequent this blog and others, but is notable in that BMS is the first to have their proof of principle phase II data using just a combination of two DAA agents (no ribavirin or pegylated interferon in the mix) to achieve an SVR12 of 36% in null responder patients, 100% SVR12 in this same population with the addition of ribavirin and pegylated interferon. To put into perspective how powerful these two agents appear to be, keep in mind that a casual comparison to Telaprevir plus P/R  in a similar patient population generated an SVR of ~ 33% (never a good idea to causally compare anything, let alone two separate clinical trials, but it gives us a ballpark estimate for general potency). One hopes that the addition of a third drug in the Daclatasvir and Asunaprevir combination targeting an additional part of the HCV life cycle could raise the SVR12 rate significantly above 36%.  For the time being, however, it looks like pegylated interferon and ribavirin  in combination with these two powerful DAA drugs are essential components in preventing resistance in this patient population. This fact also further bodes well for BMS in that, unless I lost track somewhere, they are also the owners of PEG-lamda which potentially has a leg-up in terms of efficacy and tolerability over the current pegylated interferons currently on the market.  I haven't heard much about their plans for PEG-lamda development lately. Feel free to correct or update me if I missed something. 


press release

Jan. 18, 2012, 5:01 p.m. EST

First Hepatitis C Treatment Data Demonstrating Proof of Principle with Direct-Acting Antiviral-only Therapy Published

Study also Demonstrated 100% Sustained Virologic Response 12-Weeks Post Treatment with Quadruple Therapy
 

PRINCETON, N.J., Jan 18, 2012 (BUSINESS WIRE) -- --Phase II Investigational Data Published Today in the New England Journal of Medicine

Bristol-Myers Squibb Company today announced the full results, published in the New England Journal of Medicine, from a Phase II clinical trial in patients with hepatitis C virus (HCV) genotype 1 who had not responded to prior therapy with PEG-interferon alfa and ribavirin ('null responders'(1)). The study demonstrated that its primary endpoint of the achievement of sustained virologic response 12-weeks post-treatment (SVR12) is possible with a direct-acting antiviral (DAA)-only combination containing daclatasvir and asunaprevir (4/11 patients, including two of two patients infected with HCV genotype 1b). This study was the first study to demonstrate the possibility that hepatitis C can be cured (defined as sustained virologic response 48 weeks post-treatment or SVR48) without the use of interferon. The study also demonstrated that 100 percent (10/10) of these difficult-to-treat patients dosed with quadruple therapy containing daclatasvir and asunaprevir in combination with PEG-Interferon alfa and ribavirin achieved SVR12.

In this study there were no serious adverse events on treatment or discontinuations due to adverse events. Diarrhea was the most common adverse event in both groups (73% and 70%).

"Even with the recent approval of two protease inhibitors, treatment of hepatitis C patients who have not responded to PEG-interferon alfa and ribavirin has limited success. Because of this high unmet medical need, there is a necessity for new combination regimens that can increase response rates in null responders," said lead investigator Anna Lok, MD, FRCP, director of clinical hepatology and professor in the department of internal medicine at the University of Michigan Medical School in Ann Arbor. "The data seen in this study with Bristol-Myers Squibb's investigational DAAs daclatasvir and asunaprevir, either as DAA-only therapy or as part of quadruple therapy, are encouraging as we work to advance hepatitis C therapy for this difficult-to-treat patient population. This study also shows for the very first time that sustained viral responses can be achieved without the use of interferon and ribavirin."

Daclatasvir is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials and is currently in Phase III development. Asunaprevir is an investigational, oral, selective NS3 protease inhibitor.

Study Results

Viral Response: Dual DAA Therapy with daclatasvir and asunaprevir (Group A)

Eleven patients were randomized to receive dual DAA therapy for 24 weeks. Seven of the 11 patients (64%) in Group A achieved undetectable viral load by week four, and five patients remained undetectable at the end of treatment. Of these 11 patients, one patient relapsed at four (4) weeks post treatment while four patients (36%) had sustained virological response at 12 weeks post-treatment (SVR12). In follow-up to 48-weeks post treatment, no additional cases of viral relapses were observed.

Six patients, all with HCV genotype 1a, experienced viral breakthrough on dual DAA therapy, and analysis of HCV sequences following breakthrough confirmed resistance to both antivirals. With the addition of PEG-interferon alfa and ribavirin to their regimen (rescue therapy), four of the six patients achieved undetectable viral load. Two of these patients relapsed following the treatment period and two remained undetectable, one with 14 weeks and one with 42 weeks of post treatment follow-up. Two of the six patients did not achieve undetectable HCV RNA and treatment was discontinued.

Viral Response: Quadruple Therapy with daclatasvir, asunaprevir and PEG-Interferon alfa and ribavirin (Group B)

Ten patients were randomized to receive quadruple therapy for 24-weeks. Six of the 10 patients (60%) in Group B achieved undetectable HCV RNA by week four. Ten of the 10 patients (100%) were undetectable by the end of treatment, and all 10 achieved SVR12. No patients experienced viral relapse during 48 weeks of post-treatment observation.

Safety

In the study, there were no serious adverse events on treatment, no deaths, and no treatment discontinuations due to adverse events. Most adverse events were mild to moderate, and the most common AEs were diarrhea (group a:8/11)(group a:73%)(group b:7/10)(group b:70%), fatigue (group a:6/11)(group a:55%)(group b:7/10)(group b:70%), headache (group a:5/11)(group a:45%)(group b:5/10)(group b:50%), and nausea (group a:2/11)(group a:18%)(group b:5/10)(group b:50%).

Six patients (four from group A, including two receiving rescue therapy, and two from group B) experienced elevated liver enzymes [ALT >3x upper limit of normal (ULN)] which did not require treatment discontinuation or dose interruptions, and all patients stabilized or improved with continued therapy. Six patients, all of whom received PEG-interferon alfa and ribavirin, experienced Grade 3 or 4 neutropenia, a blood disorder characterized by an abnormally low number of white blood cells.

About the Study

This open-label, phase IIa study evaluated the antiviral activity and safety of the combination of daclatasvir and asunaprevir with and without PEG-Interferon alfa and ribavirin in 21 HCV genotype 1 null responders. Patients in the study were randomized to receive one of two treatment regimens for 24 weeks. The 11 patients in Group A received dual-DAA therapy with daclatasvir 60 mg once daily and asunaprevir 600 mg twice daily, both taken orally. The 10 patients in Group B received quadruple therapy with daclatasvir 60 mg once daily, asunaprevir 600 mg twice daily, PEG-interferon alfa 180 ug once weekly, and ribavirin 1000-1200 mg daily (according to body weight) in two divided doses. The primary study objective was to determine the proportion of patients achieving undetectable viral load (HCV RNA <10 IU/mL) 12 weeks post-treatment (SVR12). This dual-DAA combination is now in Phase III development.

About Bristol-Myers Squibb's Commitment to Liver Disease

Bristol-Myers Squibb is advancing a portfolio of compounds that aims to address unmet medical needs across the liver disease continuum, including hepatitis C, hepatitis B and liver cancer. The Company's hepatitis C pipeline includes a portfolio of compounds with different mechanisms of action, pursuing both biologics as well as small molecule antivirals. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies. Discovered by Bristol-Myers Squibb through a genomics approach, daclatasvir, also known as BMS-790052, is the first NS5A replication complex inhibitor to be investigated in hepatitis C clinical trials and is currently in Phase III development. Asunaprevir, also known as BMS-650032, is an NS3 protease inhibitor in Phase III development for hepatitis C.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C, with genotype 1 being the most prevalent genotype. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a potentially 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.

(1) Null responders -- patients whose virus did not respond to prior treatment with PEG-interferon alfa and ribavirin (HCV RNA decrease <2 log10 at 12 weeks).

SOURCE: Bristol-Myers Squibb Company

New CCO Module: Update of HCV Resistance from AASLD 2011

New Clinical Care Options CME Module now online: Update on HCV Resistance from AASLD 2011
Christoph Sarrazin, MD, reviews new data on resistance to direct-acting antiviral agents from the 2011 American Association for the Study of Liver Diseases conference. (Registration required)

Topics covered include:

New data on resistance to boceprevir and telaprevir
New data on resistance to second-wave and second-generation HCV protease inhibitors
Key findings on resistance to daclatasvir, an NS5A inhibitor
Current understanding of resistance to PSI-7977, a nucleotide polymerase inhibitor
New data on resistance to oral combination HCV therapies