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

Seeking Alpha.com: Will Medgenics Become The Next Hepatitis C Take Over Candidate?

Posted on 3/12/12 on Seeking Alpha.com. The following comments by the Viral Matters editor: Seeking Alpha contributor Ray Dirks speculates that Medgenics - with it's proprietary EPODURE (for anemia) and INFRADURE (for interferon) biopump devices - would be an attractive candidate for take over. EPODURE might be a go, but the market for INFRADUR could be severely limited to disease states outside of HCV if 'interferon free' therapy becomes a reality.  As it is only in preclinical trials, INFRADUR has plenty of time to see where the 2nd and 3rd generation of anti-HCV Direct Acting Antivirals take us

Will Medgenics Become The Next Hepatitis-C Take Over Candidate?

By Ray Dirks - Seeking Alpha

Interest in the hepatitis-C space has been hot since the euphoria of Big Pharma's acquisition of Inhibitex (INHX) and others began to spread further in early January. Smaller biotechs are being snapped up by larger pharmaceutical companies driven by the need to pump up their product pipelines.

Last November, Gilead Sciences (GILD) bought Princeton, NJ-based Pharmasset for $11 billion for the next generation of hepatitis-C treatments. Vertex Pharmaceuticals, working with Merck, is offering a pill for hepatitis-C, but it has to be taken three times a day though stands the chance to make $2 billion in a couple of years, when approved.

Then there was the Bristol-Myers Squibb (BMY) acquisition of Inhibitex for $2.5 billion and Roche's (RHHBY.PK) purchase of Anadys Pharmaceuticals for $230 million. Let's not forget that Novartis (NVS) and Enanta Pharmaceuticals are in collaboration to develop and sell a brand-new hepatitis-C inhibitor for nearly $500 million.

When one looks at Medgenics (MDGN), at a market cap of only $46 million, we have have to wonder how a company with an innovative approach to treating hepatitis-C would not be of interest to a bigger pharmaceutical partner or buyer. The firm has a very unique way to treat the disease which may not have been recognized by investors yet, but we're betting that will soon change.

Last month when shares were trading at around the $3.50 level, we made a case for the disruptive technology being developed by Medgenics, focusing on the value it has for the $90 billion protein therapy market that is projected to grow to over $130 million over the next several years. Shares nearly doubled after that report and have since seen a healthy pull back.

We've looked specifically at Medgenic's EPODURE product, a proprietary biopump that produces erythropoietin within the patient's own body, now in Phase I/II clinical trials to treat anemia in chronic kidney disease. The anemia market is dominated by Amgen's Epogen that carries with it a high price tag and serious side effects.

Now we'd like to draw attention to another of Medgenic's products in development, using its biopump technology - INFRADURE, that produces interferon-alpha and is currently in the preclinical stage for the treatment of hepatitis-C. In the U.S., hepatitis-C ranks second only to alcoholism as a cause of liver disease and is the leading reason for liver transplants. The Center for Disease Control and Prevention estimates that 3.2 million people in the U.S. have chronic hepatitis-C (far out-passing HIV) and costs due to treating the disease now exceed $600 million each year, with a projection of growing to $11 billion in 2019.

Interferon, or the more popular form, peginterferon-alpha, is usually used in combination with ribavirin, another antiviral medication. Treatment is expensive, around $20,000 per year for a 48-week injected dose, which puts it out of reach in developing countries where it is badly needed. Further, only 50% of patients benefit. There is clearly a medical call for a cheaper and more effective drug.

Medgenic's INFRADURE provides an answer. Like EPODURE and other products under development, INFRADURE uses Medgenic's biopump platform technology where the patient's own tissue, taken during a biopsy, is processed then inserted into the biopump to continuously produce and deliver interferon-alpha, a natural protein produced by the body. Also like EPODURE, this approach would eliminate weekly and expensive injections, particularly since Hepatitis-C progresses very slowly.

Two drugs are on the market to treat hepatitis-C: Pegasys, made by Genentech and PEG-Intron, made by Schering-Plough. Both are meant for weekly injections. Both are very similar and meant to be used in combination with ribavirin. Side effects for this combination are startling, the most reported ones being mental illness, thoughts of hurting or killing yourself or others, unusual thoughts or behaviors, the compulsion to use street drugs if they had been used in the past, alcohol abuse, and aggressiveness. Heart disease and autoimmune disorders are also common. Pegasys and PEG-Intron used with ribavirin causes birth defects or death in an unborn baby.

For example,the FDA's review of Schering Plough's application for PEG-Intron included a number of patients that either committed or attempted suicide, murdered others, relapsed to drug or alcohol addiction, and underwent severe depression. As we mentioned, heart attacks and heart valve disease also appeared, as well as lupus, extremely low red blood cell count, kidney failure, partial blindness, and hearing loss.

INFRADURE will go into human clinical trials in the first half of this year. Based on laboratory and animal data that reported up to six months of consistent delivery of interferon-alpha, Phase I clinical trial results should show efficacy based on results seen with EPODURE.

We draw your attention to the value of Medgenic's platform technology. Besides anemia and hepatitis-C, Medgenic's product is being designed for use in hemophilia, multiple sclerosis, arthritis, obesity and diabetes.

We advise our readers to watch this company going forward as we continue to expect even more bullish developments and positive news flow going forward.

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

Barclays analyst on GILEAD and IDENIX....

Original article posted on StreetInsider.com 2/10/12 - This is an article a good friend pointed out to me earlier today. If a combo of one nucleoside inhibitor and ribavirin can become a dominant therapy type for HCV - a virus notorious for excessively high, error-prone replication and an uncanny ability to evade the host immune system - then I'm in.  To my mind however, that's either excessively positive thinking or a typo.


Barclays on U.S. Pharma: A New Era for Hep C Therapy - Starts Coverage on GILD & IDIX

Analyst, C. Anthony Butler, said, "The race towards developing the second-generation of direct antivirals (DAAs) may be a dead-heat. By the end of this decade, we believe two dominant therapy types will emerge for hepatitis C (HCV) patients: 1) a combination of a nucleotide polymerase inhibitor (Nuc) and ribavirin; and 2) a cocktail of a nucleotide polymerase inhibitor and one or two DAAs of other mechanisms."

"GILD has leapfrogged competitors through the bold acquisition of Pharmasset, and its stock move (+32.7% YTD vs NASDAQ +11.8%) reflects the market sentiment that GILD is leading the HCV race. We estimate that GILD could capture ~40% of the US HCV market by 2020 and US sales would peak at $2.8B in 2017."

"IDIX needs to find a home for its Nuc IDX184 in order to remain a contender."

Currently, shares of IDIX are trading down 1.25% and shares of GILD are flat on the session.

Top Hepatitis C Virus Biotech Picks By The World's Largest Fund Managers

Recently posted on the Seeking Alpha.com financial website on who fund managers like in the HCV drug development space. In general, fund managers are bullish like Idenix, Dynavax and Peregrine but the currently bears run wild for Vertex, Achillion and Merck. Good quick rundown of what each company specializes in and where they're HCV compounds are in terms of development and partnerships. 

The announcement by Bristol-Myers Squibb (BMY), just over two weeks ago, on January 7th, of an agreement to buy Inhibitex (INHX) for $2.5 billion at a massive buyout premium of over 160%, has ignited a rally among biotech companies that are currently active in developing products targeting hepatitis C virus (HCV). In this article, we examine based on our research of their latest available Q3 institutional 13-F filings, the investment activities of the world's largest funds or mega funds among a dozen pharmaceutical and biotech companies that are active in the HCV space.

These mega fund managers hold between $100 billion and over a trillion dollars in assets, such as Fidelity Investments, Goldman Sachs, and Vanguard Group, and together they control almost a third of the assets invested in the U.S. equity markets, but number just over 30 out of the tens of thousands of funds that invest in the U.S. equity markets. Individually, and collectively, they pack enough firepower to move stocks based on their trading activities.

Taken together, these mega managers were bullish on the group, adding a net $427 million in Q3 to their prior $178.84 billion prior quarter holdings in the group. However, taking out the big pharmaceutical companies, mega funds still added a net $530 million in Q3 to their $47.46 billion prior quarter position among the biotech companies that are active in the HCV field. (for more general information on these mega funds, please look at the end of the article).

The following are the HCV group companies that mega fund managers are bullish about (see Table):

Idenix Pharmaceuticals (IDIX): IDIX engages in the discovery and development of drugs for the treatment of human viral and other infectious diseases, including a focus on hepatitis C virus, hepatitis B virus (HBV), human immunodeficiency virus (HIV) type-1, and acquired immune deficiency syndrome (AIDS). Mega funds added a net $45 million in Q3 to their $380 million prior quarter position, and together they hold 29.7% of the outstanding shares, higher than their 26.3% weighting in the group. The top mega fund buyers in Q3 was by Fidelity Investments ($50 million), and the top holders were Fidelity Investments ($131 million), T Rowe Price ($114 million) and Vanguard Group ($50 million).

IDIX shares have mounted a strong rally recently, up more than 100% in the past twelve trading days, benefiting from both the January 9th announcement of the acquisition of rival INHX by BMY that has ignited a rally in the group, as well as positive interim phase 2b clinical trial data on its HCV Nucleotide Inhibitor, IDIX 184, that was released the same day by the company.

Dynavax Technologies (DVAX): DVAX is a clinical-stage biotech company that is engaged in the discovery and development of novel products to prevent and treat infectious and inflammatory diseases. Its lead clinical stage product candidate is HEPLISAV™, a phase 3 investigational adult hepatitis B vaccine designed to provide protection with fewer doses than current licensed vaccines. In addition it has early stage product candidates, including a universal flu vaccine in phase 1, TLR inhibitor for lupus in phase 1, and then hepatitis B and hepatitis C therapies, also in phase 1 development.

Mega funds added a net $7 million in Q3 to their $102 million prior quarter position, and taken together they hold 25.8% of outstanding shares. The top mega fund buyers were Fidelity Investments ($3.3 million) and Bank of America Corp. ($1.6 million), and the top holder by far was also Fidelity Investments ($64 million). DVAX is currently engaged in preparing to submit its first Biologics License Application (BLA) for HEPLISAV™ Hepatitis B Vaccine to the FDA in the first quarter of 2012, followed soon by a submission of Marketing Authorization Application (MAA) for European approval.

Peregrine Pharmaceuticals (PPHM): PPHM is a clinical-stage biotech company developing and manufacturing innovative monoclonal antibody therapeutics to treat cancers and viral infections such as hepatitis C virus. In the hepatitis C space, the company is evaluating bavituximab combined with ribavirin in a randomized phase 2 trials in treatment native patients with genotype-1 HCV infection. Earlier, the company released preliminary phase 2 trial results from this study on December 29th last year that showed antiviral activity and a positive safety profile, with patients reporting fewer side effects than in the interferon-containing arm. Mega funds added a net $1 million in Q3 to their $8 million prior quarter position, and taken together mega funds hold 11.4% of the outstanding shares, with the top holders at the end of Q3 being Barclays Global Investors ($2.7 million) and Blackrock ($1.7 million).

The following are the HCV group companies that mega fund manager are most bearish about (see Table):

Vertex Pharmaceuticals (VRTX): VRTX engages in the discovery, development, and commercialization of small molecule drugs for the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases. It has two FDA-approved drugs, INCIVEKTM for treat chronic hepatitis C genotype-1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatments, and Lexiva for HIV that it co-discovered with GlaxoSmithKline (GSK).

It has five other drugs in clinical development, including VX-222 in phase 2 development for hepatitis C, VX-765 in phase 2 development for epilepsy, VX-509 in phase 2 development for immune-mediated inflammatory disease, and VX-770 and VX-809 in phase 3 and phase 2 development respectively for Cystic Fibrosis. Mega funds cut a net $110 million in Q3 form their $3.89 billion prior quarter position. The top sellers were Fidelity Investments ($91 million) and T Rowe Price ($34 million), and the top holders were Fidelity Investments ($966 million) and Capital World Investors ($653 million).

Achillion Pharmaceutical (ACHN): ACHN is a clinical-stage biotech focused on developing new treatments to patients with infectious diseases, including HCV and resistant bacterial infections. It currently has five compounds in various stages of clinical development targeting HCV, including one in phase 2, two in phase 1 and two others in pre-clinical development. Mega funds cut a net $6 million from their $280 million prior quarter position, with the top seller being Bank of New York Mellon Corp. ($18 million), and the top holder being Fidelity Investments ($111 million). ACHN shares rallied strongly after the announcement of the INHX acquisition by BMY, up over 50% in the five trading days after the January 7th announcement; while they have given back part of their gains, they are still up over 35% on the news.

Inhibitex Inc. and Bristol-Myers Squibb Co.: INHX, a developer of differentiated anti-infective products to prevent and treat serious viral and bacterial infections, including primarily shingles and chronic infections caused by hepatitis C virus, is under agreement to be acquired by BMY, a developer of branded pharmaceuticals for the treatment of cardiovascular, virological and other infectious diseases. Mega funds cut $28 million in Q3 from a $512 million prior quarter position in INHX, and they added a net $711 million to their $20.51 billion prior quarter position in BMY.

Other pharmaceutical and biotech companies that are players in the HCV space that mega funds are bearish on (see Table) include Gilead Sciences Inc. (GILD), that has multiple product candidates in phase 1 and phase 2 trials targeting hepatitis C, in which mega funds cut a net $306 million in Q3 from their $17.68 billion prior quarter position, and Abbott Laboratories (ABT), that has a product candidate in phase 2 clinical trials for HCV in collaboration with Enanta Pharmaceuticals, in which mega funds cut a net $16 million in Q3 from their $26.63 billion prior quarter position.

Also, additional HCV players that mega funds are bullish about include Merck & Co. (MRK), that has an FDA-approved product Victrelis for HCV in the market, and several in phase 2 and 3 development for hepatitis B and C, in which mega funds added a net $530 million to their $47.46 billion prior quarter position; and Pfizer Inc. (PFE), that has a compound in phase 2 development for HCV, in which mega funds added a net $60 million to their $54.03 billion prior quarter position. Furthermore, mega funds have a $1 million position, unchanged in Q3, in Inovio Pharmaceuticals (INO), that has compounds in phase 2 and preclinical development targeting HCV.

General Methodology and Background Information: The latest available institutional 13-F filings of over 30+ mega hedge fund and mutual fund managers were analyzed to determine their capital allocation among different industry groupings, and to determine their favorite picks and pans in each group. These mega fund managers number less than one percent of all funds and yet they control almost half of the U.S. equity discretionary fund assets. The argument is that mega institutional investors have the resources and the access to information, knowledge and expertise to conduct extensive due diligence in informing their investment decisions. When mega Institutional Investors invest and maybe even converge on a specific investment idea, the idea deserves consideration for further investigation. The savvy investor may then leverage this information either as a starting point to conduct his own due diligence.

Credit: Historical fundamentals including operating metrics and stock ownership information were derived using SEC filings data, I-Metrix® by Edgar Online®, Zacks Investment Research, Thomson Reuters and Briefing.com. The information and data is believed to be accurate, but no guarantees or representations are made.

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

Disclaimer: Material presented here is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. Further, these are our 'opinions' and we may be wrong. We may have positions in securities mentioned in this article. You should take this into consideration before acting on any advice given in this article. If this makes you uncomfortable, then do not listen to our thoughts and opinions. The contents of this article do not take into consideration your individual investment objectives so consult with your own financial adviser before making an investment decision. Investing includes certain risks including loss of principal.