Achillion announces positive POC data for ACH-3102...

Posted 9-27-12 on the Achillion website. Achillion announces positive proof-of-concept data with it's second generation pan-genotypic NS5A inhibitor, ACH-3102. A single-dose of ACH-3102 in GT1a resulted in a mean maximum 3.74 log10 reduction in HCV RNA (range 2.9 - 4.6 log10). In addition, ACH-3102 looks to have a unique resistance profile and generally is well-tolerated.  Two patients in the proof-of-concept trial were found to have baseline resistance mutations common to the first generation HCV NS5A inhibitor class - the L31M (patient had a maximum HCV RNA decline of 3.4 log10 with the 300mg dose) and Y93C mutation  (patient had a maximum HCV RNA decline of 4.6 log10 with the 300mg dose). Data in two patients with resistance mutations with a single-dose of ACH-3102 can't nearly be labeled as definitive, but it has positive implications in terms of sequential therapy.  That Gilead's co-formulated GS-7977/GS-5885 tablet will likely be on the market well before ACH-3102, 'first rescue' for GS-7977/GS-5885 failures would potentially be an attractive niche for ACH-3102. 

The company also expects results from it's Phase II trial looking at the interferon-free, all-oral regimen of ACH-3102 + RBV for 12  weeks in GT1b patients to be available in the 4th quarter of this year. 



September 27, 2012
Achillion Announces Positive Proof-of-Concept Data With ACH-3102

-Second-Generation Pan-Genotypic NS5A Inhibitor Achieves Potent Antiviral Activity
of Mean Maximum 3.74 Log10 Reduction Following a Single Dose -

- Initiated Enrollment in a Phase 2 Clinical Trial Evaluating ACH-3102 Plus Ribavirin for the Treatment of HCV Genotype 1b-

- Hosting Analyst Day Today With Live Webcast Beginning at 1:00 p.m. ET -

NEW HAVEN, Conn., Sept. 27, 2012 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced positive proof-of-concept results with ACH-3102, a second-generation pan-genotypic NS5A inhibitor being developed for the treatment of chronic hepatitis C viral infections (HCV). Administration of a single-dose of ACH-3102 to genotype (GT) 1a HCV-infected subjects resulted in a mean maximum 3.74 log10 reduction in HCV RNA (range 2.9 — 4.6 log10). Significant reductions in HCV RNA were achieved in subjects with resistant variants at baseline, including L31M and Y93C variants.

Based on these data, combined with safety and tolerability results from the Phase 1a trial in healthy subjects evaluating up to 14 days of ACH-3102, Achillion has initiated a pilot Phase 2 clinical trial evaluating ACH-3102 in combination with ribavirin for the treatment of patients with chronic GT 1b HCV.

"We believe these proof-of-concept results demonstrate the differentiation of ACH-3102 from first-generation NS5A inhibitors. The potency of ACH-3102 was successfully shown against genotype 1a, historically the hardest to treat HCV subtype," commented Michael Kishbauch, President and Chief Executive Officer of Achillion. "Furthermore, we believe the enhanced resistance profile of ACH-3102 observed in vitro has been validated in the clinic with robust antiviral activity against baseline mutations such as L31M. These results support our belief that this second-generation pan-genotypic NS5A inhibitor has the potential to become a cornerstone compound."

ACH-3102: Phase 1 Program

In May 2012, Achillion initiated a Phase 1a clinical trial evaluating the safety and tolerability of single and multiple ascending doses of ACH-3102 in healthy volunteers. To date, 42 healthy volunteers have received a single dose of ACH-3102, ranging from 25 mg to 1,000 mg. An additional 32 healthy volunteers have received 14 days of ACH-3102 once-daily evaluating various dosing regimens. Preliminary data from the single and multiple ascending dose groups demonstrated that ACH-3102 was well tolerated at all doses evaluated. There were no serious adverse events and 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.

In August 2012, Achillion initiated a Phase 1b clinical trial enrolling a total of 14 patients infected with GT 1a chronic HCV, of which 2 received placebo and 12 received a single dose of 50 mg, 150 mg or 300 mg ACH-3102. No serious adverse events were reported and there were no patient discontinuations.

The mean maximum HCV RNA decline for each dose group is provided below:


      Mean maximal   Range decline
  Dose   decline HCV RVA HCV RNA
Genotype (mg) N (log10) (log10)
  50 4 3.78 3.35 — 4.16
1a 150 4 3.52 2.91 — 3.98
  300 4 3.93 3.40 — 4.60
  Placebo 2 0.72 --

An assessment of clinical virology was conducted on baseline samples from all 12 patients receiving a single-dose of ACH-3102. Sequencing revealed one patient had a baseline L31M mutation (300 mg dose group, maximum HCV RNA decline of 3.4 log10) and another patient had a baseline Y93C mutation (300 dose group, maximum HCV RNA decline of 4.6 log10). These mutations have been previously reported to convey a high level of resistance to first-generation NS5A inhibitors which was not observed following exposure to ACH-3102.

ACH-3102: All-oral, interferon-free pilot Phase 2 12-week trial of ACH-3102 and ribavirin for the treatment of HCV GT 1b

Achillion has initiated patient enrollment in an open-label Phase 2 pilot trial evaluating 12-weeks of once-daily ACH-3102 in combination with ribavirin for the treatment of HCV GT 1b. This study will initially enroll up to 16 treatment-naïve patients with GT 1b IL28B CC HCV. Patients will receive 225 mg of ACH-3102 on day 1 followed by 75 mg of ACH-3102 once daily on subsequent days in combination with twice daily ribavirin. The primary objective of the trial is to determine the safety and sustained virologic response 12 weeks after the completion of treatment (SVR12) with secondary endpoints assessing safety, pharmacokinetics, pharmacodynamics, and virologic endpoints including rapid virologic response (RVR) and extended RVR (eRVR). Achillion expects to report initial RVR results from this study during the fourth quarter of 2012.

Mr. Kishbauch further commented, "With the initiation of this all-oral 12-week study evaluating ACH-3102 and ribavirin for the treatment of HCV genotype 1b, we have rapidly advanced our portfolio and believe the attributes of ACH-3102, as well as sovaprevir, our Phase 2 protease inhibitor, have the potential to provide optimized compounds for the broad treatment of HCV."

Analyst Day Webcast

Achillion is hosting its inaugural Analyst Day and simultaneous webcast on Thursday, September 27, 2012 at 1:00 p.m. Eastern Time. To access a copy of the presentation and the live audio webcast of the event, please visit www.achillion.com. Please connect to Achillion's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary. A replay of the webcast will be available on www.achillion.com beginning approximately 2 hours after the conclusion of the event.

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 favorable activity and potential benefits of ACH-3102 and sovaprevir, and expectations about milestone achievement including the potential to report RVR results during the fourth quarter of 2012. 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 the positive results found in nonclinical studies and earlier stage clinical studies of sovaprevir, ACH-2684, and ACH-3102; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and its subsequent SEC filings.

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

CONTACT: Company Contact:

         Glenn Schulman

         Achillion Pharmaceuticals, Inc.

         Tel. (203) 624-7000

         gschulman@achillion.com



         Media:

         Christin Culotta Miller

         Ogilvy PR

         Tel. (646) 229-5178

         christin.miller@ogilvypr.com

       

         Investors:

         Mary Kay Fenton

         Achillion Pharmaceuticals, Inc.

         Tel. (203) 624-7000

         mfenton@achillion.com



         Investors:

         Seth Lewis

         The Trout Group, LLC

         Tel. (646) 378-2952

         slewis@troutgroup.com

Vertex Pharmaceuticals / Alios BioPharma HCV nuc update...

Posted on 9-25-12 on ClinicaSpace.com. Vertex Pharmaceuticals will continue to develop one nucleotide inhibtior in it's collaboration with Alios BioPharm, ALS-2200 (also known as VX-135), while ending development of ALS-2158 due to lack of efficacy. Vertex is planning on moving ALS-2200 to an all-oral, interferon-free combination Phase II trial in genotype 1 patients later this year. 

Vertex Pharmaceuticals Incorporated (VRTX) Ends Work on One Hepatitis C Drug, Continues Another; Stock Down

9/25/2012 7:41:57 AM

CAMBRIDGE, Mass., Sep 25, 2012 (BUSINESS WIRE) -- --- ALS-2200: Data from additional cohort of seven-day viral kinetic study with ALS-2200 (200 mg, QD) in combination with ribavirin show median 4.18 log10 reduction in HCV RNA with 5 of 8 people below the limit of quantification; treatment was well-tolerated -

Vertex Pharmaceuticals Incorporated and its collaborator Alios BioPharma, Inc. today announced results from a viral kinetic study of the adenosine nucleotide analogue pro-drug ALS-2158 for the treatment of hepatitis C. Data showed that seven days of dosing with up to 900 mg of ALS-2158 was well-tolerated in people with genotype 1 chronic hepatitis C, but that there was insufficient antiviral activity to warrant proceeding with further clinical development. The companies also announced new data from an additional cohort of an ongoing viral kinetic study of the uridine nucleotide analogue pro-drug ALS-2200 in combination with ribavirin. There was a median 4.18 log10 reduction from baseline in HCV RNA after seven days of dosing with a once-daily 200 mg dose of ALS-2200 in combination with ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment (n=8). Five patients achieved HCV RNA levels below the limit of quantification

Similar to previously announced data from the monotherapy cohort, ALS-2200 was well-tolerated, no patients discontinued due to adverse events and there were no serious adverse events. Data from the ALS-2200 study will be presented in an oral presentation at The Liver Meeting(R), the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, November 9 to 13, 2012.

"Our goal is to develop all-oral regimens that are well-tolerated and provide a high rate of viral cure in a broad population of people with chronic hepatitis C," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "We're making good progress and expect to begin all-oral Phase 2 combination studies by the end of this year."

Pending discussions with regulatory agencies, Vertex is planning one Phase 2 study to evaluate ALS-2200 (VX-135) in combination with ribavirin, and one to evaluate ALS-2200 (VX-135) in combination with INCIVEK(R) (telaprevir), the company's approved protease inhibitor for people with genotype 1 chronic hepatitis C. These studies will evaluate 12 total weeks of treatment with a primary endpoint of SVR12 (sustained viral response:undetectable hepatitis C virus 12 weeks after the end of treatment) in people with genotype 1 chronic hepatitis C.

About ALS-2200

ALS-2200 is a uridine nucleotide analogue pro-drug that appears to have a high barrier to drug resistance based on in vitro studies. It is designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. In vitro studies of the compound showed antiviral activity across all genotypes, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.

Vertex gained worldwide rights to ALS-2200 through an exclusive licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that will focus on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.

About INCIVEK

INCIVEK(R) (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication.

INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for use in combination with pegylated-interferon and ribavirin for adults with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously with interferon-based treatment but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).

Vertex developed telaprevir in collaboration with Janssen and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO(R) in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and is known as Telavic(R).

IMPORTANT SAFETY INFORMATION

Indication

INCIVEK(R) (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.

Important Safety Information

INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines. Hormonal forms of birth control, including birth control pills, vaginal rings, implants or injections, may not work during treatment with INCIVEK.

INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

INCIVEK can cause serious side effects including skin reactions, rash and anemia that can be severe. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com .

About Hepatitis C

Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.(1) Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.(1) Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.(1)

Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.(2) However, approximately 60 percent of people do not achieve SVR,(3,4,5)or viral cure,(6) after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.(7,8)

More than 170 million people worldwide are chronically infected with hepatitis C.(6) In the United States, up to 5 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.(9,10)Hepatitis C is four times more prevalent in the United States compared to HIV.(10) The majority of people with hepatitis C in the United States were born between 1945 and 1965, accounting 82 percent of people with the disease.(11)Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.(12,13)By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.(10)

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and for three years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences.

Vertex's press releases are available at www.vrtx.com .

About Alios BioPharma

Alios BioPharma is a biotechnology company located in South San Francisco, California, that is developing novel medicines aimed at the treatment of viral diseases. Alios has an innovative team of highly experienced scientists and clinical researchers who are developing direct acting antiviral agents against several human viral pathogens of public health importance including HCV, RSV, Influenza and other chronic, acute and emerging viral diseases. The overall goal for the Alios therapeutic platform is to maximize patient benefits in areas of high unmet medical need through optimization of potency, safety and tolerability.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Kauffman's statements in the third paragraph of this press release and statements regarding (i) data supporting the advancement of ALS-2200 into Phase 2 all-oral studies this year and (ii) Vertex's plans regarding the design of these Phase 2 studies. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the initiation of Phase 2 studies of ALS-2200 may be delayed or prevented, outcomes from any future studies of ALS-2200 may not be favorable and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com . Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

References:

(1) Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June 2010. Accessed September 21, 2012.

(2) Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.

(3) Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.

(4) Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.

(5) McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.

(6) Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

(7) Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

(8) Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

(9) Chak, E, et. al. Hepatitis C Virus Infection In USA: An Estimate of True Prevalence. Liver Intl. 2011;1096 -1098.

(10) Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx Updated January 11, 2010. Accessed September 21, 2012.

(11) Smith, BD, et al. Hepatitis C Virus Antibody Prevalence, Correlates and Predictors among Persons Born from 1945 through 1965, United States, 1999-2008. AASLD 2011 Annual Meeting.

(12) Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

(13) S.D. Holmberg, K.N. Ly., et.al. The Growing Burden of Mortality Associated with Viral Hepatitis in the United States, 1999-2007. AASLD 2011 Annual Meeting.

SOURCE: Vertex Pharmaceuticals Incorporated

Medivir announces interferon-free phase IIa trial with HCV PI plus investigational non-nuc...

Press release  posted 9/20 on PR Newswire. Medivir announces a Phase IIa trial pairing it's HCV NS3/4A protease inhibitor simeprevir (TMC435) with Janssen's non-nuc TMC647055 and ritonovir (a potent CYP P450 inhibitor) with and without ribavirin in treatment naive, relapser genotype 1 patients as well as the difficult-to-treat genotype 1a null responder population. The latter population is incredibly important, as the efficacy with current anti-HCV regimens is notoriously low. The addition CYP P450 inhibitor ritonavir is used in regimens to block metabolism of the active molecule(s) leading me to believe that TMC435 may effect the drug levels of TMC647055, or both. Ritonavir, unfortunately, also limits concomitant meds also metabolized by CYP P450.  

A Phase IIa Interferon Free Combination Hepatitis C Trial of Simeprevir (TMC435) and TMC647055 Will Commence Shortly

STOCKHOLM, September 20, 2012 /PRNewswire/ --
Medivir AB (OMX: MVIR), announced today that simeprevir (TMC435) and TMC647055, a non-nucleoside inhibitor (NNI) will enter a phase IIa interferon free combination trial.

Simeprevir is a once daily potent HCV NS3/4A protease inhibitor in phase III clinical development for the treatment of chronic hepatitis C jointly developed by Medivir and Janssen Research & Development Ireland (Janssen). TMC647055 is a potent NNI (non-nucleoside inhibitor) of the HCV NS5B polymerase and is being developed by Janssen R&D.

"This study is in line with Medivir's and Janssen's strategy to evaluate different combination possibilities with simeprevir for interferon-free HCV treatments. This will broaden our understanding of simeprevir, which we believe has the necessary characteristics to potentially become a key component of future hepatitis C treatment regimens, including combination with interferon and ribavirin as well as interferon-free therapies," comments Charlotte Edenius, Medivir's EVP of Research and Development.

Study design
This will be an open label study in patients who are chronically infected with HCV genotype-1a or 1b to assess the efficacy, safety and tolerability of the combination. The primary endpoint in the study will be SVR12 (sustained virologic response 12 weeks after end of treatment). Simeprevir, TMC647055 and low-dose ritonavir will be co-administered once daily, with and without ribavirin.

Approximately 40 patients will be enrolled in this study, which is divided in two parts. The first part will include patients chronically infected with HCV genotype-1, who are either treatment-naive or have relapsed after prior pegylated interferon (PegIFN)/ribavirin treatment. The treatment will consist of simeprevir, TMC647055 and low-dose ritonavir, with and without ribavirin for 12 weeks.

The second part of the trial will investigate the same regimen in prior null responder patients chronically infected with HCV genotype 1a.

Additional information about this study will be posted on http://www.clinicaltrials.gov

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 Research & Development Ireland.
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: http://www.medivir.com
For more information about Medivir, please contact:

Medivir
Rein Piir, EVP Corporate Affairs & IR  
Direct: +46-8-440-6550 or:
Mobile: +46-708-537-292

M:Communications
Europe: Mary-Jane Elliott, Amber Bielecka, Hollie Vile  
medivir@mcomgroup.com
+44(0)20-7920-2330

SOURCE Medivir

PR Newswire (htt

Sofosbuvir (GS-7977) in HIV/HCV co-infected patients...

Posted 9/17/12 on Hep Mag.com. A small interferon-free Phase Ib 7-day trial of Sofosbuvir (GS-7977) plus ribavirin in 19 HIV/HCV co-infected patients yielded some impressive initial results in a population that is definitely in need of more anti-HCV options. Sofosbuvir showed no difference in viral kinetics vs non co-infected patients, no new safety signals, no HIV viral breakthrough and no added side-effects. Hopefully the larger Phase III trial in this population will be equally impressive in its results. 

Sofosbuvir (GS-7977) Shows Promise in HIV/Hep C-Coinfected People

Gilead Sciences' experimental NS5B polymerase inhibitor sofosbuvir (GS-7977) was just as likely to rapidly reduce hepatitis C virus (HCV) levels in people coinfected with HIV, compared with those living with HCV but not HIV, in a small seven-day study presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco. The clinical trial, which enrolled HCV/HIV-coinfected and HCV-monoinfected patients residing in Puerto Rico—75 percent of whom had difficult-to-treat genotype 1 HCV infection—also noted that side effects were no different or more severe among those with living with both viruses. After a week of sofosbuvir treatment, used without other hep C medications, HCV viral loads dropped by an average of 4 log (99.99 percent). Additionally, nearly 60 percent of patients achieved undetectable HCV viral loads during the study, with 15 percent maintaining undetectable levels seven days after treatment was discontinued. Sofosbuvir appeared to work equally well against the different HCV genotypes in the study and did not hinder the effectiveness of the antiretroviral regimens being used to suppress HIV. A Phase III clinical trial of sofosbuvir plus ribavirin enrolling people living with HCV and HIV began in July and is currently recruiting volunteers.

Journal of Medical Case Reports: Classic polyarteritis nodosa associated with hepatitis C virus infection: a case report

Interesting case report posted 9-14-12 on Journal of Medical Case Reports.com. Lately, there has been quite a bit of medical literature discussing the extrahepatic burden of disease associated with HCV. This is a case report of a patient diagnosed with HCV-related Polyarteritis Nodosa (often misdiagnosed as mixed cryoglobulinemia). Polyarteritis Nodosa is a Polyarteritis Nodosa is an inflammatory disease that damages arteries and the tissues the arteries feed also become damaged to to lack of oxygen and nourishment. Again, this points to the premise that although in most cases fibrosis progression is slow within the liver, that there are other extrahepatic risks associated with replicating HCV virus

Case report

Classic polyarteritis nodosa associated with hepatitis C virus infection: a case report
Damith Rodrigo, Ruwan Perera and Janaka de Silva

Journal of Medical Case Reports 2012, 6:305 doi:10.1186/1752-1947-6-305
Published: 14 September 2012

Abstract (provisional)

Introduction
Hepatitis C virus has been under-recognized as an etiologic factor for polyarteritis nodosa and the presence of hepatitis C antigenemia in patients with polyarteritis nodosa has been reported as insignificant. In the literature hepatitis C virus-associated polyarteritis nodosa is a rare and controversial entity.

Case presentation
A 34-year-old Sri Lankan Tamil man presented to our facility with a two-week history of slow-resolving pneumonia of the right mid and lower zones. On physical examination he had panniculitic type tender skin nodules with background livedo reticularis. A skin biopsy was suggestive of a small and medium vessel vasculitis compatible with polyarteritis nodosa. He was tested positive for hepatitis C antibodies. A serum cryoglobulin test was negative but perinuclear antineutrophilic cytoplasmic antibody test was positive. Serum complement levels were reduced. He was diagnosed as having classic polyarteritis nodosa associated with hepatitis C infection. He later developed left-sided radiculopathy involving both upper and lower limbs and an ischemic cardiac event. His hepatitis C infection was managed with polyethylene glycol-interferon 2alpha combined with oral ribavirin. Simultaneously, his classic polyarteritis nodosa was treated with prednisolone and cyclophosphamide. He made a good recovery.

Conclusions
Hepatitis C virus infection is capable of inducing a fulminant form of vasculitis in the form of polyarteritis nodosa. It may be easily confused early in its course with mixed cryoglobulinemia, which is commonly known to be associated with hepatitis C virus. Awareness of hepatitis C virus-related polyarteritis nodosa helps in diagnosing the condition early so combined immunosuppressive and antiviral treatment can be started as soon as possible.

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

JID: 'Chronic Hepatitis C Virus Infection Increases Mortality From Hepatic and Extrahepatic Diseases: A Community-Based Long-Term Prospective Study'

I reference this study entitled 'Chronic Hepatitis C Virus Infection Increases
Mortality From Hepatic and Extrahepatic Diseases: A Community-Based Long-Term
Prospective Study' from the "Journal of Infectious Diseases" all the time in conversation and seem to get a good discussion going. I'm hoping for the same outcome on the Internet, thus this post. This is a HUGE cohort study from China (n = 23,820). Grant it, the 'n' representative of the HCV seropositive population is rather small (1095) compared to the seronegative population (19,636), and the population is of Eastern descent, but even given the sampling and ethnic disparity, there are compelling conclusions here which bear further study. Most notably, that having replicating Hepatitis C virus results in not only greater hepatic-related mortality, but extra-hepatic as well. Replicating virus = inflammation of all types. This gives compelling fuel to treatment advocates arguments that, barring contraindications and other special cases, Hepatitis C-positive patients should be considered for treatment now vs 'warehousing' for drugs that might/might not make it to market in the future. Hopefully further prospective and retrospective data based on the conclusions here will shed more light on this controversial subject. 

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.