January 13, 2014

Liver International

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Review Article

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Gloria Searson1, Ellen S. Engelson2,  Damaris Carriero1,3, Donald P. Kotler1,2,*

DOI: 10.1111/liv.12467

This article is protected by copyright. All rights reserved.

Publication History
Accepted manuscript online: 13 JAN 2014 01:05AM EST
Manuscript Accepted: 6 JAN 2014
Manuscript Revised: 25 DEC 2013
Manuscript Received: 27 JUN 2013

Keywords: effectiveness research;  health disparities;  substance abuse; alcoholism;  chronic liver disease

Abstract

Hepatitis C infection is an important problem in inner city neighborhoods, which suffer from multiple health disparities. Important factors in this population include alcoholism and substance abuse, mental illness, and homelessness, which may be combined with mistrust, poor health literacy, limited access to health care, and outright discrimination. Systemic barriers to effective care include a lack of capacity to provide comprehensive care, insufficient insurance coverage, poor coordination among caregivers and between caregivers and hospitals, as well as third party payers. These barriers affect real world treatment effectiveness as opposed to treatment efficacy, the latter reflecting the world of clinical trials. The components of effectiveness include efficacious medications, appropriate diagnosis and evaluation, recommendation for therapy, access to therapy, acceptance of the diagnosis and its implications by the patient and adherence to the recommended therapy. Very little attention has been given to assisting the patient to accept the diagnosis and adhere to therapy, i.e., care coordination. For this reason, care coordination is an area in which greater availability could lead to greater acceptance/adherence and greater treatment effectiveness.

This article is protected by copyright. All rights reserved.

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ACH

Jan. 13, 2014

NEW HAVEN, Conn., Jan. 13, 2014 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today reported progress on the Company's portfolio of proprietary compounds for the treatment of chronic hepatitis C (HCV) and outlined its 2014 milestones.

"We believe that we have the broad portfolio of HCV compounds necessary to succeed in achieving our primary goal of developing commercially competitive short duration therapies for the treatment of HCV that are once-daily and ribavirin-free. With the emerging safety and in vitro data on ACH-3422, a uridine nucleotide inhibitor of NS5B polymerase, and the 12-week clinical activity reported with ACH-3102, our Phase 2, pan-genotypic, second-generation NS5A inhibitor, we believe that our HCV compounds are well-positioned to achieve positive results in the clinical studies we plan to initiate throughout 2014," commented Dr. Milind Deshpande, President and Chief Executive Officer of Achillion. "With our 2013 year-end cash balance projected to exceed $150 million, we believe we have sufficient capital to fund our operations into 2016 and achieve a number of value-creating milestones throughout this year with our HCV assets."

2014 Milestones

  • ACH-3422: HCV Nucleotide NS5B Polymerase Inhibitor

-  To date, all of the Company's preclinical studies support the advancement of ACH-3422 into clinical trials. Achillion expects to initiate a Phase 1 first-in-human trial ex-US during the second quarter of 2014, subject to regulatory approval, followed by a Phase 1 proof-of-concept trial in mid-2014. Achillion anticipates reporting initial results from HCV-infected patients in the third quarter of 2014.

  • ACH-3102 + sofosbuvir

-  Achillion plans to initiate a pilot Phase 2 study early in the second quarter of 2014 evaluating the combination of ACH-3102, a second-generation NS5A inhibitor in Phase 2, with sofosbuvir in treatment-naive HCV patients over treatment durations of 8 weeks or less. The study aims to optimize the use of ACH-3102 in nucleotide-based regimens and to expedite the development of the combination of ACH-3102 and ACH-3422. 

  • ACH-3422 + ACH-3102 ± NS3/4A protease inhibitor

- Achillion anticipates the initiation of an all-oral Phase 2 combination study evaluating ACH-3422 by year-end 2014, and anticipates the initiation of a Phase 2 combination study evaluating ACH-3422 and ACH-3102, with and without an Achillion NS3/4A protease inhibitor, in treatment-naive HCV patients over treatment durations of 8 weeks or less in early 2015.

  • ACH-3102 + ACH-2684

- Achillion intends to evaluate the combination of its NS5A inhibitor ACH-3102, and next-generation NS3/4A protease inhibitor, ACH-2684, in a Phase 1 drug-drug interaction study that is expected to begin in the first quarter of 2014.

- The Company also plans to initiate a proof-of-concept study evaluating this combination in genotype 1b HCV-infected patients over a treatment duration of 8 weeks in mid-2014 to enable future combination studies.

Sovaprevir: NS3/4A Protease Inhibitor

- Achillion is preparing a complete response package on the previously disclosed sovaprevir clinical hold and anticipates a response from the FDA by the end of the first half of 2014.

- In the ongoing Phase 2 -007 trial evaluating 12-week treatment with sovaprevir, ACH-3102, and ribavirin in combination, to date all patients with chronic genotype 1b HCV infection have maintained 100% virologic response despite the presence of multiple resistant mutations at baseline in the NS5A protein. As anticipated by the viral breakthroughs previously reported in genotype 1a patients, the combination of sovaprevir and ACH-3102 is not being pursued as a treatment for chronic genotype 1a HCV infection. Achillion intends to submit these study results for presentation at a scientific conference in 2014.

"We are very pleased with the overall progress across our broad HCV portfolio. We believe that the clinical strategy outlined for 2014 will enable us to move toward delivering commercially competitive treatment regimens for HCV," commented Dr. David Apelian, M.D., Ph.D., Chief Medical Officer at Achillion. "Furthermore, with Achillion's broad portfolio of assets, we believe that the addition of an NS5B nucleotide inhibitor, such as ACH-3422, could achieve very competitive cure rates across broad patient populations with a treatment regimen of 8 weeks or less."

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. 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.

Cautionary Note Regarding 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 potential benefits and prospects for Achillion's portfolio of HCV compounds; expectations regarding clinical study results in 2014; Achillion's projected year-end cash balance, its expectations as to the period in which such cash will be available to fund its operations, and the prospects for such cash enabling it to achieve milestones; the Company's 2014 milestone goals, including with respect to advancing compounds into and through clinical development and obtaining data readouts from trials of its compounds; and its plans and timing with respect to the FDA clinical hold on sovaprevir. Achillion may use words such as "expect," "anticipate," "project," "intend," "plan," "aim," "believe," "seek," "estimate," and "may" and similar expressions to identify such forward-looking statements. Among the important 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: demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; advance the preclinical and clinical development its drug candidates, including ACH-3422, ACH-3102 and ACH-2684, under the timelines it projects in current and future clinical trials; satisfactorily respond to the clinical hold placed on sovaprevir by the FDA; obtain and maintain necessary regulatory approvals; obtain and maintain 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; manage litigation; raise the substantial additional capital needed to achieve its business objectives; and successfully execute on its business strategies. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2013 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 duty to update any forward-looking statement, except as required by applicable law.

Company Contact:

         Glenn Schulman

         Achillion Pharmaceuticals, Inc.

         Tel. (203) 624-7000

         gschulman@achillion.com 

         Media:

         Emily Johnson

         Ogilvy PR

         Tel. (212) 880-5316

         emily.johnson@ogilvy.com

         Investors:

         Mary Kay Fenton

         Achillion Pharmaceuticals, Inc.

         Tel. (203) 624-7000

         mfenton@achillion.com

         Investors:

         Lee Stern

         The Trout Group, LLC

         Tel. (646) 378-2922

         lstern@troutgroup.com

Contact

 

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logga-top-enkel-se

Stockholm, Sweden—Medivir AB (OMX: MVIR), announces that Idenix Pharmaceuticals, Inc. today released interim data from the ongoing phase II HELIX-1 clinical trial evaluating an all-oral, direct-acting antiviral (DAA) HCV combination regimen of samatasvir (IDX719), Idenix’s once-daily pan-genotypic NS5A inhibitor, and simeprevir , a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, and ribavirin.

The combination regimen of the study was well-tolerated. In the treatment-naïve, non-cirrhotic, genotype 1b or 4 HCV-infected patients receiving 50 mg of samatasvir and 150 mg of simeprevir plus ribavirin for 12 weeks, 85 percent (n=17/20) of the patients achieved SVR4 (undetectable HCV RNA four weeks after end of treatment). The 50 mg dose of samatasvir is the selected dose in the ongoing 3-DAA HELIX-2 clinical trial. The HELIX-1 study results are expected to be presented at a scientific meeting in 2014.

HELIX-1 study design
The HELIX-1 trial is the first study in HCV-infected patients to commence under a non-exclusive collaboration agreement between Idenix and Janssen which was established in January 2013. The HELIX-1 trial is a phase II 12-week, randomized, parallel group study evaluating the antiviral activity, safety and tolerability of samatasvir and simeprevir in treatment-naïve, non-cirrhotic, genotype 1b or 4 HCV-infected patients.

Patients in part A of the study (n=63) were enrolled in one of three treatment groups receiving 50, 100, or 150 mg samatasvir once-daily for 12 weeks in combination with 150 mg of simeprevir plus a weight-based dose of ribavirin. In part B of the ongoing HELIX-1 study, exploratory cohorts of patients have been added to evaluate the safety and antiviral activity of a 25 mg dose of samatasvir in genotype 1b-infected patients and of a 100 mg dose of samatasvir in genotype 6-infected patients.

A second phase II trial (HELIX-2) was initiated in December 2013 evaluating samatasvir, simeprevir and TMC647055, a once-daily non-nucleoside polymerase inhibitor plus a low-dose ritonavir being developed by Janssen, with and without ribarivin in genotype 1-infected patients who are either treatment-naïve or have previously relapsed after treatment with pegylated interferon and ribavirin.

For additional information about the HELIX-1 study, please visit www.clinicaltrials.gov

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 13.15 p.m. CET on 13 January 2014.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in HCV genotype 1 and 4 infected subjects with compensated liver disease, including cirrhosis.

Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan (trade name Sovriad™) and in the USA (trade name Olysio™) and Canada (trade name Galexos™) in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 and genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.

About Samatasvir (IDX719)
Samatasvir is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, samatasvir has been safe and well-tolerated after single and multiple doses of up to 150 mg in healthy volunteers up to 14 days duration, and in HCV-infected patients up to 12 weeks duration. There have been no treatment-emergent serious adverse events reported in the program. Samatasvir has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log10 IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.

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, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

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

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