April 21, 2012

Celebrate the Hep C Wins, for Now

By Brian Orelli, The Motley Fool

Posted 8:36AM 04/21/12 Posted under: Investing

The data dump at this week's European Association for the Study of Liver Disease for hepatitis C drugs is nothing short of amazing. Early data suggests the drugs are working really well without the need for Merck's (NYS: MRK) PegIntron or Roche's Pegasys, which have to be injected and have unpleasant side effects.

  • Gilead Sciences' (NAS: GILD) GS-7977 plus ribavirin looked good in multiple studies. Between 59% and 88% of patients had early cure rates. Good thing, since it paid $11 billion for Pharmasset, mainly for this drug.
  • GS-7977 worked even better in combination with Bristol-Myers Squibb's (NYS: BMY) daclatasvir, with early cure rates between 91% and 100%, depending on the strain of virus.
  • Daclatasvir plus another Bristol drug, asunaprevir, hit a 77% cure rate, but that isn't too shabby, since it was in difficult-to-treat patients and was measured 24 weeks after treatment. The early cure rates -- measured four weeks after treatment -- in the GS-7977 trials are preliminary and will probably come down a little.
  • Don't forget about Abbott Labs (NYS: ABT) . The company doesn't get as much press -- not making acquisitions will do that -- but combining two of its drugs with ribavirin resulted in an 82% cure rate 36 weeks after treatment. Another combination looked even better, with cure rates between 93% and 95%, although that was only after 12 weeks of treatment.

No doubt, those are rule-breaking results. Add a few more drugs to the cocktail, and we might have long-term cure rates approaching 100%.

But investors should keep in mind that these are only phase 2 studies. The drugs still have to go through the final stage of clinical trials before they can go in front of the FDA. With hepatitis C drugs, efficacy data typically translates well from phase 2 to phase 3. The bigger risk is that side effects might crop up when the drugs are tested in a larger population. Data from one of the Abbott trials, for instance, was based on a whopping 11 patients.

The trials will also take some time to complete. Vertex Pharmaceuticals (NAS: VRTX) presented phase 2 data for Incivek as early as late 2006 and didn't get the hepatitis C drug approved until last May. It probably won't take quite that long for this generation of drugs, but the drugs are still years away from an approval.

Enjoy the data party; just realize revenue from the drugs is a way away and still not guaranteed.

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NJ Poison Control Issues Advisory on Hepatitis Prevention

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A hotline is available for information and support regarding HIV/AIDS and STD's. 6:00 am

Editor's Note: The following information is a release from New Jersey Poison Information and Education System at UMDNJ.

Being infected with HIV and the hepatitis C virus (HCV) is cause for great concern. Although HIV and HCV share similar modes of transmission (i.e. injection drug use, organ transplants, blood transfusions, unprotected sexual encounters, and neonatal transmission), HCV is mainly transmitted through direct blood contact. Because this virus is spread through exposure to infected blood, injection drug users (IDUs) are at serious risk for coinfection. According to Centers for Disease Control and Prevention (CDC), it is estimated that 50% to 90% of injection drug users with HIV are also infected with HCV.

The hepatitis C virus (HCV) is the most common cause for liver disease (Hepatitis) in this country. Liver disease has become a leading cause of illness and death among people living with HIV; HCV infection is much more serious in HIV-infected persons. Studies have shown that coinfection resulted in more rapid progression to HCV-related liver disease and increased risk for HCV-related cirrhosis and liver cancer. It can also impact the course and management of HIV infection.

The CDC recommends the following to prevent HCV infection:

  • Stop injecting drugs
  • Do not share personal hygiene items that can be contaminated with blood like toothbrushes, razors, etc.
  • Body piercing and/or tattooing may put you at risk for infection with any bloodborne pathogen if dirty needles or other instruments are used
  • Practice safe sex

The New Jersey AIDS/HIV/STD Hotline highly recommends that everyone be tested for the hepatitis C virus, including HIV-infected persons. Treatment is available for those diagnosed with hepatitis C and may be life saving if done early. The hotline is available to answer questions concerning HIV/AIDS, STDs or Hepatitis. Call for free educational materials. All calls are free and confidential.

The following services are available 24 hours a day/7 days a week:

  • Referrals
  • HIV, STD and Hepatitis Prevention Information
  • Counseling and Treatment Locations
  • Treatment Information

To Reach the New Jersey AIDS/HIV/STD Hotline, call 1-800-624-2377

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Presido

PRESS RELEASE

April 21, 2012, 2:00 a.m. EDT

Pre-Clinical Profile to be Presented at the 47th European Association for the Study of the Liver (EASL) Meeting

SAN FRANCISCO, Apr 21, 2012 (BUSINESS WIRE) -- Presidio Pharmaceuticals, Inc. announced today that PPI-383, a novel non-nucleoside polymerase inhibitor to treat hepatitis C virus (HCV), has been nominated for clinical development and will be profiled by Richard Colonno, Ph.D., Chief Scientific Officer, in poster 1173 at the 47th Annual EASL meeting being held in Barcelona, Spain on April 21st, 2012.

PPI-383 is a potent, pan-genotypic inhibitor of HCV discovered at Presidio, which exhibits a favorable pharmacokinetic and safety profile in multiple animal species following oral dosing. PPI-383 binds to the Palm II pocket of the HCV polymerase (NS5B) and possesses excellent biochemical and pharmaceutical properties critical to successful drug development, including a potential for once-daily oral dosing and minimal potential for drug-drug interactions. PPI-383 is currently undergoing further preclinical evaluation to support initiation of clinical studies alone and in combination with PPI-668 next year.

PPI-383, identified through an extensive medicinal chemistry effort, exhibits EC50s of 8.3 and 2.2 nM in HCV 1a and 1b replicon assays, respectively. PPI-383 is also active against other major HCV genotypes (2a, 3a and 4a) in stable replicon cell assays (EC50s of 4.4-11.7 nM). "The selection of PPI-383 underscores Presidio's continued commitment to generate best-in-class compounds for treating HCV," commented Dr. Colonno, who added, "It is an excellent complement to our lead NS5A inhibitor, PPI-668, currently completing Phase 1b clinical studies. We intend to develop oral, combination regimens that possess potent, pan-genotypic activity." The distinct mechanism of action of PPI-383 will potentially allow its use in combination regimens with all other classes of HCV inhibitors.

Poster 1173, entitled "Identification and Characterization of PPI-383, a Next Generation HCV NS5B Non-Nucleoside Inhibitor with Potent Activity Against all Major HCV Genotypes" will be presented by Dr. Colonno on Saturday, April 21st, 2012 at the Centre Convencions Internacional Barcelona (CCIB) from 8:00 AM to 5:00 PM.

About HCV

Chronic hepatitis C is a persistent, potentially progressive inflammatory liver disease caused by chronic infection with the hepatitis C virus (HCV). Worldwide, there are an estimated 130 to 170 million persons with chronic HCV infection, with over 350,000 deaths occurring each year.

The current standard treatment for hepatitis C in the United States, for patients with HCV genotype-1 infection, is combined administration of pegylated-interferon-alfa, ribavirin, and an HCV protease inhibitor. This multi-drug treatment is characterized by incomplete efficacy for HCV genotype-1 patients, variations in efficacy according to patients' underlying human genetic factors, no established efficacy for patients infected with other HCV genotypes, severe side effects in some patients, and dosing inconveniences. In countries where the current HCV protease inhibitors are not yet regulatory-approved, standard treatment is only pegylated-interferon-alfa plus ribavirin, which is less effective.

There is a continuing need for all oral, more consistently effective and better tolerated antiviral combinations for HCV infection, regardless of HCV genotype, patient genetic factors, or disease stage.

About Presidio

Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics. For more information, please visit our website at: www.presidiopharma.com .

SOURCE: Presidio Pharmaceuticals, Inc.

Source

ACH

April 21, 2012

 

Posters Detailing ACH-1625, ACH-3102 and ACH-2928 Presented at the International Liver Congress(TM) 2012

NEW HAVEN, Conn., April 21, 2012 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN), a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today announced that in the second segment of its Phase 2a trial of ACH-1625, 94 to 100 percent of patients with treatment naïve genotype 1 chronic hepatitis C virus (HCV) achieved a complete early virologic response (cEVR) after 12 weeks of treatment with ACH-1625 in combination with pegylated interferon alfa-2a and ribavirin (P/R). ACH-1625 in combination with P/R for up to 12 weeks was safe and well tolerated and produced high viral response rates regardless of dose level or IL28B genotype status.

Results from this trial were presented during the 47th Annual Meeting of the European Association for the Study of the Liver (EASL) International Liver Congress 2012 in Barcelona, Spain from April 18 — 22, 2012. Additional posters detailing Achillion's NS5A inhibitor program, including ACH-2928 and ACH-3102, were also presented during EASL

Michael D. Kishbauch, President and Chief Executive Officer of Achillion commented, "We are extremely pleased with the safety and efficacy that ACH-1625 has achieved in this Phase 2 clinical trial as well as the impressive resistance profile this compound has shown to date. As we finalize this Phase 2 trial and report on SVR later this year, we are now focused on initiating our all-oral program for the treatment of HCV. With the recent submission of an IND for ACH-3102, our second-generation NS5A inhibitor, we look forward to initiating its Phase 1 program this quarter and rapidly advancing toward a therapeutic, interferon-free combination trial evaluating ACH-1625 plus ACH-3102 during the fourth quarter of this year."

ACH-1625: Phase 2 protease inhibitor for the treatment of HCV

In Segment 2 of this Phase 2a trial, a total of 58 subjects with HCV were enrolled, randomized and stratified by IL28B genotype, including CT and TT, which is a marker of a patient's responsiveness to interferon, to receive one of three doses of once-daily ACH-1625 (200 mg, 400 mg or 800 mg) in combination with P/R for 12 weeks of therapy.

Of the patients enrolled, 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. No viral breakthroughs were observed during treatment. Results demonstrated rapid virological response (RVR) at week 4, cEVR and end of treatment (EOT) responses for patients returning for EOT visit to date as follows:

 

ACH-1625
200 mg 400 mg 800 mg
Segment 2: 12-week treatment duration assessments n=19 n=20 n=19
RVR (HCV RNA < 25 IU/mL week 4), % (n) 79% (15/19) 89% (16/18) ** 90% (17/19)
cEVR (undetectable week 12), 100% (18/18) * 94% (15/16) ** 100% (19/19)
% (n)
EOT Response (undetectable) *** % (n) 86% (6/7) 69% (9/13) 100% (10/10)
Reasons for discontinuation include: *200 mg 1 patient withdrew for unrelated AEs at Week 5. **400 mg 1 patient withdrew consent at Week 9, 1 patient moved at Week 2, each were undetectable at the time of withdrawal; 2 patients withdrew for unrelated AEs, one before Week 4 and one before Week 12. ***EOT denominator includes only patients who returned for their end of treatment visit

Safety results from both segments of the trial were similar to those observed and previously reported during clinical trials of ACH-1625. Most reported adverse events (AEs) in patients receiving ACH-1625 were classified as mild to moderate and were transient. The most common AEs were consistent with pegylated interferon alfa-2a and ribavirin treatment. During 12 weeks of co-administration of ACH-1625 plus P/R, there was one reported serious adverse event (SAE) that was deemed unrelated to ACH-1625. There was no difference noted between dose groups for either the incidence or severity of observed adverse events.

"We were pleased to note that across the dose groups and regardless of IL28B status, nearly all patients treated through 12 weeks achieved cEVR. The clinical potency, unique pharmacokinetic profile, and barrier to resistance for ACH-1625 appear to provide very effective antiviral coverage for all of these genotype 1 patients," commented Dr. Elizabeth A. Olek, Chief Medical Officer of Achillion. "With the continued on-treatment viral suppression and impressive initial end of treatment response rates, we look forward to reporting out the sustained viral response rates for these patients later in the year."

In a separate poster presentation, the clinical virology of NS3 variants from patients enrolled in Segment 1 of the Phase 2a clinical trial evaluating multiple ascending doses of ACH-1625 in combination with P/R was presented. Sequencing of baseline to post-treatment samples revealed that there were no mutations at loci 155, 156, or 168 of NS3 protease, which represent common mutations that may confer resistance to protease inhibitors. To date, no viral breakthrough has been observed during monotherapy with ACH-1625 or with ACH-1625-based treatment regimens suggesting that the potency of ACH-1625 is sufficient to inhibit the growth of the most frequently observed resistant mutants.

Additional NS5A Inhibitor Posters Presented at EASL

- Preclinical characteristics of ACH-3102: A novel HCV NS5A inhibitor with improved potency against genotype 1a virus and variants resistance to 1st generation of NS5A inhibitors (abstract A845. Y. Zhao, et al.)

- Novel NS5A inhibitor ACH-2928 phase 1 results in HCV GT-1 patients (abstract 1211. B. Vince, et al.)

About ACH-1625

ACH-1625 is a Phase 2 pan-genotypic HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. ACH-1625 has demonstrated rapid and extensive partitioning to the liver, as well as high liver/plasma ratios. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50 of approximately 1nM. ACH-1625 has shown clinical antiviral activity against genotypes 1 and 3. Fast Track status was granted to ACH-1625 in 2012 for the treatment of chronic HCV.

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 nearly 4 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 hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000 begin_of_the_skype_highlighting 1-203-624-7000 end_of_the_skype_highlighting.

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 ACH-1625; and Achillion's expectations regarding timing for the completion and reporting of additional results of Phase 2 clinical trials of ACH-1625 and the commencement of a Phase 1 clinical trials of ACH-1625 plus ACH-3102. 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 clinical trials of ACH-1625 and its other product candidates; 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; 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) 752-5510

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

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