Data from Phase 3 Studies of Gilead’s Sofosbuvir for Hepatitis C To Be Presented at 48th Annual EASL Meeting; Findings Published Online Today in The New England Journal of Medicine

AMSTERDAM--(BUSINESS WIRE)--Apr. 23, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that detailed results from four Phase 3 clinical trials (NEUTRINO, FISSION, POSITRON and FUSION) evaluating sofosbuvir, the company’s investigational once-daily nucleotide NS5B inhibitor for the treatment of chronic hepatitis C virus (HCV) infection, will be presented this week in oral sessions at the 48th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2013) in Amsterdam, The Netherlands. In addition, detailed results from the four clinical studies have also been published online in two papers, ahead of print, in The New England Journal of Medicine (NEJM).

In the four trials, sofosbuvir was administered to nearly 1,000 patients with chronic HCV infection as part of an all-oral 12-week or 16-week treatment regimen in combination with ribavirin (RBV) in genotypes 2 and 3, or with RBV and pegylated interferon (peg-IFN) for 12 weeks in genotypes 1, 4, 5 and 6. Overall SVR12 rates (sustained viral response 12 weeks after completing therapy) from 50 to 90 percent were observed. Patients who achieve SVR12 are considered cured of their HCV infection.

A description of the four Phase 3 studies and SVR12 results are summarized in the table below. Detailed results from the Phase 3 studies of sofosbuvir are available at www.nejm.org/online-first.

Sofosbuvir Phase 3 Studies
Study		Population		Treatment groups		SVR12 Rates
NEUTRINO		Genotype 1/4/5/6 treatment-naïve		Sofosbuvir + RBV + Peg-IFN for 12 weeks		90% (295/327)
FISSION		Genotype 2/3 treatment-naïve		Sofosbuvir + RBV for 12 weeks or		67% (107/253)
				Peg-IFN + RBV for 24 weeks		67% (162/243)
POSITRON		Genotype 2/3, IFN intolerant, ineligible or unwilling		Sofosbuvir + RBV for 12 weeks or		78% (161/207)
				Placebo for 12 weeks		0% (0/71)
FUSION		Genotype 2/3 treatment-experienced		Sofosbuvir + RBV for 12 weeks or		50% (50/100)
				Sofosbuvir + RBV for 16 weeks		73% (69/95)

“There remains an urgent unmet medical need for individuals diagnosed with chronic hepatitis C infection,” commented Ira Jacobson, MD, Chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, The Joan Sanford I. Weill Medical College of Cornell University, Attending Physician, New York-Presbyterian Hospital Cornell Campus. “The breadth of data from the Phase 3 program evaluating sofosbuvir will help physicians understand how to treat the disease in the future across various HCV genotypes and patient populations.”

“In these particular studies, sofosbuvir-based HCV therapy demonstrated high efficacy rates and a favorable safety profile while reducing the need for interferon injections to 12 weeks, or eliminating interferon completely from the regimen,” said Eric Lawitz, MD, President and Medical Director, The Texas Liver Institute, University of Texas Health Science Center, San Antonio. “Based on these findings, sofosbuvir, once approved, has the potential to play an important role in addressing the global hepatitis C epidemic.”

The NS5b region of the HCV viral genome for all patients who relapsed was sequenced and no S282T mutations were observed by population or deep sequencing (1 percent cutoff). There was no change in susceptibility to sofosbuvir or RBV observed by phenotypic analyses.

With the exception of one patient in FISSION who was non-compliant, relapse accounted for all virologic failures. Adverse events were generally mild and included fatigue, nausea, headache, insomnia, pruritis, anemia and dizziness. Less than 2 percent of patients in the sofosbuvir treatment groups discontinued due to adverse events.

On April 8, Gilead submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for sofosbuvir for the treatment of HCV infection. The data submitted in the NDA support the use of sofosbuvir and RBV as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with RBV and peg-IFN for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection.

Gilead plans to file for regulatory approval of sofosbuvir in other geographies, including the European Union, in the second quarter of 2013. The European Medicines Agency (EMA) has accepted Gilead’s request for accelerated assessment for sofosbuvir, a designation that is granted to new medicines of major public health interest. Accelerated assessment could shorten the EMA’s review time of sofosbuvir by two months. Granting of accelerated assessment does not guarantee a positive opinion from the CHMP or approval by the European Commission.

About Sofosbuvir

Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B protein, which plays an essential role in HCV replication. Sofosbuvir is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication. Sofosbuvir is intended to become a cornerstone of interferon-free, all-oral treatment regimens for HCV that achieve higher cure rates more rapidly and with fewer side effects than current therapeutic options. Sofosbuvir is an investigational product and its safety and efficacy have not yet been established.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

Forward-Looking Statement

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 factors, including the risk that FDA and other regulatory agencies may not approve sofosbuvir, and that any marketing approvals, if granted, may have significant limitations on its use. Additional clinical studies of sofosbuvir, including in combination with other compounds, may not produce favorable results. As a result, Gilead may not be able to successfully commercialize sofosbuvir, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2012, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at

1-800-GILEAD-5 or 1-650-574-3000 .

Source: Gilead Sciences, Inc.

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Also See: Rapid, Sustained Response With Sofosbuvir in Hepatitis C

Rapid, Sustained Response With Sofosbuvir in Hepatitis C

Medscape Medical News > Conference News

Pam Harrison

Apr 23, 2013

Treatment with sofosbuvir results in a rapid and sustained virologic response in patients with hepatitis C virus (HCV), report investigators.

The nucleotide analogue that inhibits HCV replication is showing promise when given together with ribavirin or in addition to pegylated interferon (peginterferon) alfa-2a for a variety of genotypes and in different patient populations, new studies show.

"Interferon is always a challenging therapy and depending on the genotype we're treating, patients are going to require 6 months to a year of treatment," Eric Lawitz, MD, from the University of Texas Health Science Center in San Antonio, told Medscape Medical News.

"With sofosbuvir, patients with genotype 1 hepatitis C virus are only going to need 12 weeks of interferon, and in patients with genotype 2 and 3," Dr. Lawitz explained, "we can eliminate interferon completely so sofosbuvir offers a higher efficacy rate, a more favorable safety profile, and either a reduction in the time on interferon or its elimination entirely, which is a significant paradigm shift in the management of hepatitis C."

Results from several studies involving sofosbuvir will be presented this week at the International Liver Congress 2013 in Amsterdam, the Netherlands. The findings are published online April 23 in the New England Journal of Medicine in advance of the meeting.

NEUTRINO Trial

In the NEUTRINO open-label study, 327 patients infected with HCV genotypes 1, 4, 5, or 6 received sofosbuvir, ribavirin, and peginterferon alfa-2a for 12 weeks.

Sofosbuvir was given orally at a dose of 400 mg, once a day, along with ribavirin, also given orally in a dose based on weight. Patients who weighed less than 75 kg received 1000 mg/d, and heavier patients received 1200 mg/d. Patients received peginterferon alfa-2a subcutaneously once a week at a dose of 180 μg.

"Most of the patients who were included in the study had hepatitis C genotype1," the authors point out. Only 9% had genotype 4 and 2% had genotype 5 or 6.

In this single-group study, investigators report a sustained virologic response in 90% of patients (95% confidence interval [CI], 87% - 93%).

FISSION Trial

In the noninferiority study known as the FISSION trial, patients with hepatitis C genotype 2 or 3 were randomly assigned to 12 weeks of treatment with sofosbuvir plus ribavirin or to 24 weeks of treatment with peginterferon alfa-2a plus ribavirin. For the peginterferon-ribavirin group, the ribavirin dose was 800 mg/d given in 2 divided doses, in accordance with product labeling.

The sofosbuvir-based regimen was successful in 97% of patients with genotype 2 infection and 56% successful in those with genotype 3 infection compared with 78% and 63% in the standard peginterferon alfa-2a plus ribavirin group.

All patients receiving sofosbuvir in the 2 studies had rapid and substantial decreases in serum HCV RNA levels, the authors report. Further, the magnitude of the decrease during treatment was not substantially different between the various genotypes being treated, they point out.

By the second week after enrollment, 91% of sofosbuvir-treated patients with genotype 1, 4, 5, or 6 infection had an RNA level less than 25 IU/mL.

By week 4, this proportion had increased to almost 100%, and sustained virologic responses were maintained to study endpoint. Patients who achieve a sustained virologic response after 12 weeks of treatment are considered to be cured of hepatitis C.

Twenty-eight patients in the NEUTRINO study and 74 patients in the FISSION study who received treatment with sofosbuvir relapsed after achieving a virologic response at the end of treatment.

However, none of the RNA samples collected after therapy showed any sign of resistance-associated variants, confirming that sofosbuvir has a high barrier to resistance.

Adverse Events

Investigators report that discontinuation rates due to adverse effects were low among patients receiving sofosbuvir-containing regimens.

Among NEUTRINO patients, 2% of those receiving 12 weeks of sofosbuvir plus ribavirin with peginterferon discontinued treatment. In FISSION, just 1% of patients receiving 12 weeks of sofosbuvir plus ribavirin discontinued therapy. However, a higher rate — 11% — of patients who received 24 weeks of peginterferon plus ribavirin stopped treatment.

The most common adverse events in all groups were fatigue, headache, nausea, and insomnia. However, investigators report, influenza-like symptoms and fever, as well as depression, occurred much more frequently in patients receiving peginterferon than in those receiving sofosbuvir.

"These data demonstrate that sofosbuvir plus ribavirin will offer a significant improvement in therapy as the combination eliminates the need for interferon and it has the potential to halve treatment duration for patients with genotypes 2 and 3, which means patients could achieve cure in as little as 3 months," Dr. Lawitz said. "Should the FDA [US Food and Drug Administration] approve sofosbuvir for the treatment of hepatitis C, it could be used in all genotypes either with or without interferon and in treatment-naive, treatment-experienced and interferon-intolerant patients."

In a second paper published in the New England Journal of Medicine and scheduled to be presented at the International Liver Congress this week, researchers led by Ira Jacobson, MD, from Weill Cornell Medical College in New York unveil the findings from 2 new clinical trials of sofosbuvir.

POSITRON Trial

In 1 study, known as the POSITRON trial, patients who could not take peginterferon received sofosbuvir and ribavirin or placebo.

The primary endpoint for the trial was virologic response at 12 weeks. Investigators report that the rate of sustained virologic response was 78% (95% CI, 72% - 83%) among patients receiving sofosbuvir and ribavirin, compared with 0% among those receiving placebo (P < .001).

There was reportedly complete concordance (100%) between rates of sustained virologic response at 12 weeks and at 24 weeks among patients who received sofosbuvir and ribavirin; none of the 153 patients who could be evaluated had virologic relapse after week 12.

FUSION Trial

In the second study, known as the FUSION trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 or 16 weeks.

The rates of sustained virologic response achieved with sofosbuvir and ribavirin in the population of patients with prior treatment were superior to the historical control rate of 25%, with rates of 50% (95% CI, 40% - 60%) in the 12-week group and 73% (95% CI, 63% - 81%) in the 16-week group (P < .001).

The secondary analysis comparing rates of sustained virologic response between the groups showed that patients receiving 16 weeks of treatment had a significantly higher rate of sustained virologic response than patients receiving 12 weeks of treatment (difference, –23 percentage points; 95% CI, –35 to –11 percentage points; P < .001).

"In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection," report investigators. Among patients with genotype 3 infection, response rates were lower among those with cirrhosis.

The most common adverse events were again headache, fatigue, nausea, and insomnia, but the overall discontinuation rate was low at 1% to 2%.

In an accompanying editorial, Joost Drenth, MD, from Radboud University Nijmegen Medical Center in the Netherlands, cautioned that only 3 of 4 of the published sofosbuvir studies were randomized and only 1 was placebo-controlled

Dr. Drenth also suggested that there may be a worrisome loss of response to sofosbuvir over time that is not seen with interferon-based regimens. On the other hand, he pointed out, the NEUTRINO study involving patients with primarily genotype 1 infection, but also genotype 4, 5, and 6 HCV all responded to 12 weeks of treatment, with a collective rate of sustained virologic response of 90%.

"Sofosbuvir has ungenotypic activity, whereas other drugs target only genotype 1," Dr. Drenth told Medscape Medical News. "We can also treat these patients for a shorter period of time with sofosbuvir and there is less need for interferon. So this is all positive news and data from the sofosbuvir trials suggest that a radical change in clinical practice is imminent."

Gilead Sciences recently submitted a New Drug Application to the FDA for approval of once-daily sofosbuvir for the treatment of hepatitis C. Gilead also plans to file for regulatory approval in other countries, including in the European Union, in the second quarter of 2013.

The studies were funded by Gilead Sciences. Dr. Lawitz reports he has received research grants from multiple pharmaceutical companies.

N Engl J Med. Published online April 23, 2013. Lawitz study full text Jacobson study full text Editorial

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ALS-2200 (VX-135) Viral Kinetic Study Shows Significant Reduction in HCV RNA in People with Genotype 1 Hepatitis C Virus Infection and Cirrhosis, and in People with Genotypes 2, 3 or 4 HCV Infection

April 23, 2013

- After seven days of once-daily dosing with 200 mg of ALS-2200, genotype 1 patients with cirrhosis had a median 4.08 log₁₀ reduction in HCV RNA; among people with genotypes 3 or 4, there was a median 4.65 log₁₀ reduction in HCV RNA -

- Data are consistent with previously reported ALS-2200 results in people with genotype 1 HCV infection -

- ALS-2200 was well-tolerated, with no discontinuations due to adverse events-

AMSTERDAM--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new data from a viral kinetic study of the uridine nucleotide analogue ALS-2200 (VX-135) in development for the treatment of hepatitis C. There was a median 4.08 log₁₀ reduction in hepatitis C virus (HCV) RNA after seven days of dosing with 200 mg once daily in treatment-naïve people with genotype 1 chronic HCV infection and compensated cirrhosis. Among treatment-naïve people with genotypes 3 or 4 chronic HCV infection, there was a median 4.65 log₁₀ reduction in HCV RNA after seven days of dosing with 200 mg once daily. Prior to a protocol amendment, one treatment-naïve person with genotype 2 HCV infection received 100 mg of ALS-2200 once daily for seven days, and had a 5.04 log₁₀ reduction in HCV RNA after seven days of dosing. ALS-2200 was well-tolerated in this study, there were no serious adverse events and no patients discontinued due to adverse events. These new data are consistent with previously reported data in people with genotype 1 chronic HCV infection, and will be presented the 48th Annual Meeting of the European Association for the Study of the Liver (EASL) in Amsterdam, Netherlands, April 24 to 28, 2013 (poster #866).

These data support Vertex's recently announced non-exclusive agreement with Bristol-Myers Squibb Company to conduct Phase 2 studies of once-daily all-oral treatment regimens containing VX-135 and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir for the treatment of hepatitis C. As part of the agreement, Vertex plans to conduct two Phase 2 studies of the combination, including an initial study in treatment-naïve people with genotype 1 HCV infection planned for the second quarter of 2013. Vertex plans to begin a subsequent study in treatment-naïve people infected with genotype 1, 2 or 3 HCV, including those with cirrhosis, in the second half of 2013, pending data from the initial study.

"The viral kinetic data announced to date show the potential for VX-135 to be the backbone of all-oral treatment regimens," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "The data suggest that VX-135 holds promise as a treatment option for people with genotypes 1 through 4 HCV infection, and for people with cirrhosis, who urgently need more effective and better tolerated treatments."

Results of seven-day viral kinetic evaluations of ALS-2200 in treatment-naïve people with chronic HCV infection are included in the following table:

Cohort			Median Baseline HCV RNA (Log10 IU/mL) (Min, Max)			Median Change From Baseline After 7 Days of Treatment (Log10 IU/mL) (Min, Max)			HCV RNA Levels Below the Lower Limit of Quantification* (LLOQ) n (%)
Placebo			6.30			0.05			0 (0)
Genotypes 1, 3 and 4			(5.70, 7.35)			(-0.47, 0.66)
(n=10)
200 mg monotherapy			6.18			-4.54			4 (50)
Genotype 1			(5.66, 6.72)			(-3.81, -5.08)
(n=8)
200 mg + ribavirin			6.21			-4.18			5 (63)
Genotype 1			(5.14, 7.41)			(-3.62, -5.20)
(n=8)
200 mg monotherapy			6.64			-4.65			5 (63)
Genotypes 3 and 4			(5.59, 6.93)			(-4.05, -5.30)
(n=8)**
Placebo			6.41			0.06			0 (0)
Genotype 1			(6.36, 6.47)			(0.03, 0.10)
Cirrhotic
(n = 2)
200 mg monotherapy			6.53			-4.08			1 (13)
Genotype 1			(6.08, 7.22)			(-2.91, -4.87)
Cirrhotic
(n = 8)
*Roche COBAS® Taqman® HCV Assay v2.0 (LLOQ = 25 IU/mL)
**Prior to a protocol amendment, one person with genotype 2 HCV infection received 100 mg of ALS-2200 once daily for seven days, and had a 5.04 log10 reduction in HCV RNA after seven days of dosing.

About VX-135 (ALS-2200)

Vertex has multiple ongoing and planned studies of VX-135 as part of all-oral treatment regimens, including a study in combination with ribavirin and studies with other direct-acting antivirals. Vertex plans to begin pivotal development of VX-135 as part of all-oral treatment regimens in 2014, pending data from these studies. The first Phase 2 data for VX-135 as part of an all-oral regimen are expected in the second half of 2013.

VX-135 is a uridine nucleotide analogue pro-drug designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. ALS-2200 has shown pangenotypic activity in vitro. 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 focuses on the discovery of additional nucleotide analogues that act on the hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.

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 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.^3,4

More than 170 million people worldwide are chronically infected with hepatitis C.⁵ In the United States, up to 5 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.^6,7 Hepatitis C is four times more prevalent in the United States compared to HIV.⁷ The majority of people with hepatitis C in the United States were born between 1945 and 1965, accounting for 82 percent of people with the disease.⁸ Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.^9,10 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.¹¹

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.

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, the statements of Dr. Kauffman in the third paragraph of this press release, and statements regarding (i) the timing and structure of multiple Phase 2 studies exploring all-oral treatment regimens that include VX-135 in combination with ribavirin and/or other direct-acting antivirals, including daclatasvir; (ii) Vertex's plans to begin pivotal development of VX-135 as part of all-oral treatment regimens in 2014, pending data from this studies and (iii) the first Phase 2 data for VX-135 as part of an all-oral regimen being expected in the second half of 2013. 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 Phase 2 studies of VX-135 may be delayed or prevented, outcomes from any future studies of VX-135 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 March 29, 2013.

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 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).

⁴ 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.

⁵ Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

⁶ Chak, E, et. al. Hepatitis C Virus Infection In USA: An Estimate of True Prevalence. Liver Intl. 2011;1096 -1098.

⁷ 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 March 29, 2013.

⁸ 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.

⁹ 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.

¹⁰ Ly KN, et al. The Increasing Burden of Mortality From Viral Hepatitis in the United States Between 1999 and 2007. Ann Intern Med. 2012;156:271-278.

¹¹ Pyenson B, Fitch K, and Iwasaki K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. May 2009. Available at: http://www.vrtx.com/assets/pdfs/MillimanReport.pdf Accessed March 29, 2013.

Vertex Pharmaceuticals Incorporated
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Erin Emlock, 617-341-6992
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Nikki Levy, 617-341-6992
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New data from Simeprevir phase III studies Quest 1 and 2 in hepatitis C patients will be presented at EASL 23-28 April in Amsterdam

23-Apr-13 Stockholm, Sweden — Medivir AB (OMX: MVIR) today announces that data will be presented on the investigational protease inhibitor simeprevir (TMC435) for the treatment of genotype 1 hepatitis C patients.

These primary efficacy and safety results from two global phase III studies demonstrate that use of the investigational protease inhibitor simeprevir led to sustained virologic response 12 weeks after the end of treatment (SVR12) in 80 and 81 percent, respectively, of treatment-naïve genotype 1 chronic hepatitis C adult patients with compensated liver disease, when administered once daily with pegylated interferon and ribavirin. In both studies, 50 percent of patients receiving pegylated interferon and ribavirin alone achieved SVR12.

The data will be presented this week at The International Liver Congress 2013 of the European Association for the Study of the Liver (EASL) in Amsterdam, The Netherlands. The QUEST-1 and QUEST-2 data will also be discussed in an official EASL press conference on April 24 at 11:00 a.m. CEST.

"We are very happy about the robust high cure rates and the very good safety profile of simeprevir as demonstrated in the QUEST 1 and 2 studies both also including patients with severe liver disease and other characteristics that are predictors of more difficult to cure patients”, said Charlotte Edenius, EVP Development, Medivir AB. “ These data together with the data from a third phase III study in relapser patients (PROMISE study) form the basis for the regulatory filings which were recently submitted in both Japan and US while the EU submission is expected in the near future."

In QUEST-1 and QUEST-2, patients were randomized to receive simeprevir or placebo for 12 weeks plus pegylated interferon and ribavirin for 24 or 36 weeks. In findings related to a secondary endpoint, 85 (QUEST-1) and 91 percent (QUEST-2) of patients receiving simeprevir were able to shorten therapy with pegylated interferon and ribavirin to 24 weeks due to meeting response-guided therapy (RGT) criteria.

Of those patients meeting RGT criteria to stop treatment at 24 weeks, 91 percent (QUEST-1) and 86 percent of patients (QUEST-2) achieved SVR12.

“These data represent new and important improvements infor the future treatment of genotype 1 hepatitis C patients”, said Maris Hartmanis, Medivir’s CEO.

Patients enrolled in QUEST-1 and QUEST-2 were stratified by HCV genotype 1 subtype and IL28B genotype. In QUEST-1, among patients treated with simeprevir, SVR12 rates according to IL28B genotype were 94 percent (CC), 76 percent (CT), and 65 percent (TT). In QUEST-2, in the simeprevir arm, SVR12 rates according to IL28B genotype were 96 percent (CC), 80 percent (CT), and 58 percent (TT). Among patients with METAVIR scores F3 and F4, 70 percent of patients treated with simeprevir in QUEST-1 and 66 percent of patients treated with simeprevir in QUEST-2 achieved SVR12. Among patients with METAVIR scores F0 to F2, 83 percent of patients treated with simeprevir in QUEST-1 and 85 percent of patients treated with simeprevir in QUEST-2 achieved SVR12. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver and patients are scored on a four-point scale.

The most common adverse events seen in patients receiving simeprevir in QUEST-1 were fatigue (42 percent versus 41 percent for placebo), itch (26 percent versus 16 percent for placebo), and headache (33 percent versus 39 percent for placebo). The most common adverse events seen in patients receiving simeprevir in QUEST-2 were fatigue (37 percent versus 42 percent for placebo), itch (25 percent versus 25 percent for placebo), headache (39 percent versus 37 percent for placebo), fever (31 percent versus 40 percent for placebo), and influenza-like illness (26 percent versus 26 percent for placebo). In QUEST-1, in both the simeprevir and placebo arms, 3 percent of patients discontinued treatment due to an adverse event. In QUEST-2, 2 percent of patients in the simeprevir arm and 1 percent of patients in the placebo arm discontinued treatment due to an adverse event.

About QUEST-1 and QUEST-2

QUEST-1 and QUEST-2 are global, phase III, randomized, double-blind, placebo controlled clinical trials assessing the efficacy, safety and tolerability of simeprevir plus pegylated interferon and ribavirin versus pegylated interferon and ribavirin alone in treatment-naïve adult patients with genotype 1 chronic hepatitis C with compensated liver disease.

In the QUEST-1 and QUEST-2 trials, 394 and 391 patients, respectively, were randomized to receive one 150 mg capsule of simeprevir or placebo once daily plus pegylated interferon and ribavirin for 12 weeks, followed by pegylated interferon and ribavirin alone for either 12 or 36 weeks based on RGT criteria. Patients in the simeprevir arm were considered to have met RGT criteria if their HCV RNA levels were

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

About Simeprevir

Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Janssen and Medivir AB for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease. Janssen recently announced the submission of new drug applications for simeprevir in Japan and the United States for the treatment of genotype 1 hepatitis C.

Global phase III studies of simeprevir include QUEST-1 and QUEST-2 in treatment-naïve patients, PROMISE in patients who have relapsed after prior interferon-based treatment and ATTAIN in null-responder patients. In parallel to these trials, phase III studies for simeprevir are ongoing in treatment-naïve and treatment-experienced HIV-HCV co-infected patients and HCV genotype 4 patients.

Simeprevir is also being studied in phase II interferon-free trials with and without ribavirin in combination with:

• · Janssen’s non-nucleoside inhibitor TMC647055 and ritonavir in treatment-naïve genotype 1a and 1b HCV patients;
• · Gilead Sciences, Inc.’s nucleotide inhibitor sofosbuvir (GS-7977) in treatment-naïve and previous null-responder genotype 1 HCV patients; and
• · Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir (BMS-790052) in treatment-naive and previous null-responder genotype 1 HCV patients.

In addition, Janssen has entered into a non-exclusive collaboration with Vertex Pharmaceuticals to evaluate in a phase II study the safety and efficacy of an all-oral regimen of simeprevir and Vertex’s investigational nucleotide analogue polymerase inhibitor VX-135 for the treatment of HCV. As a first step, Janssen Pharmaceutical Inc. will conduct a drug-drug interaction (DDI) study with simeprevir and VX-135.

Janssen also has plans to initiate a phase II trial of an investigational interferon-free regimen with simeprevir, TMC647055 and Idenix’s IDX719, a once-daily, pan-genotypic NS5A inhibitor, with and without ribavirin.

For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov.

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease and liver transplants, is a rapidly evolving treatment area with a clear need for innovative treatments. Approximately 150 million people are infected with hepatitis C worldwide, and 350,000 people per year die from the disease.
About Medivir AB

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 in late phase III clinical development for hepatitis C that is being developed in collaboration with Janssen R&D Ireland. 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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Enanta Announces New Data From Phase 2b Interferon-Free Combination Studies with Protease Inhibitor ABT-450 for Hepatitis C Treatment to be Presented at EASL

Poster Presentations to Include Enanta’s Cyclophilin Inhibitor Program and Additional ABT-450 Data -

WATERTOWN, Mass.–(BUSINESS WIRE)–Apr. 23, 2013– Enanta Pharmaceuticals, Inc., (NASDAQ: ENTA), a research and
development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field, announced today that new Phase 2b data related to ABT-450, Enanta’s lead HCV protease inhibitor identified in its ongoing collaboration with AbbVie, as well as new preclinical data on Enanta’s proprietary cyclophilin inhibitor, EDP-546, will be presented at the International Liver Congress, (ILC), which is the 48^th Annual Meeting of the European Association for the Study of the Liver (EASL) taking place in Amsterdam April 24-28, 2013.

Results from “Aviator,” AbbVie’s Phase 2b clinical trial of ABT-450 combined with two of AbbVie’s proprietary investigational direct-acting antivirals (DAAs), for the treatment of hepatitis C virus (HCV) infection, continue to demonstrate high sustained viral response (SVR) rates against genotype 1 HCV, across patient types. SVR rates of 96% to 99% after 12 weeks of treatment were achieved in patients new to treatment (naïve) and 93% in patients who had previously failed treatment with pegylated interferon and ribavirin (null responders). In addition, similarly high SVR rates over 90% observed after 24 weeks of treatment in the Phase 2b trial reinforce the adequacy of the 12-week treatment duration for the investigational interferon-free, triple DAA combination. The triple-DAA combination is currently being studied in Phase 3 clinical trials. Data from the “Aviator” study will be presented during the official ILC press conference in Amsterdam on Wednesday, April 24 at 11:00 am CEST and also in an oral presentation on Thursday, April 25.

About Study M11-652 (Aviator)

The objective of this Phase 2b study was to assess the safety, and efficacy of ABT-450/r (dosed 100/100 to 200/100mg once daily), ABT-267 (25mg once daily), ABT-333 (400mg twice daily) and ribavirin in non-cirrhotic, treatment-naïve patients and prior peg-interferon/ribavirin null responders administered for 8, 12 or 24 weeks. Enrollment was open to GT1-infected patients regardless of IL28B host genotype, and ribavirin dosing was weight-based.

A summary of key data from the trial is below:

For the 12-week triple-DAA regimen with ribavirin that is being studied in the Phase 3 trials, these Phase 2b Aviator data show:

• 99% of treatment-naïve patients achieved SVR₁₂, 96% achieved SVR₂₄ in this intent-to-treatanalysis

• 93% of prior null responders achieved SVR₁₂ and SVR₂₄

• The single relapse with this regimen occurred at post-treatment week two

With the triple-DAA plus ribavirin regimen, comparable SVR₂₄ response rates were also seen in treatment naïve patients and null responder patients across HCV subtype, IL28B genotype, baseline HCV-RNA levels and severity of fibrosis.

*The fibrosis analysis was post-hoc based on biopsy or non-invasive testing at screening.

The safety profile seen in this study is consistent with the initial presentation of results in November 2012. Of the 247 patients included in this analysis, four patients (1.6 percent) discontinued the study because of drug-related adverse events. Serious adverse events were noted in 4 patients (1.6 percent), with one (arthralgia) considered possibly drug-related. Other events reported in more than 10 percent of patients included headache, fatigue, nausea, insomnia, and diarrhea. Grade 3-4 laboratory abnormalities in total bilirubin (six patients) and ALT (one patient) were noted; all resolved with continued dosing.

“Results from treatment utilizing ABT-450 in combination with other antiviral agents in AbbVie’s portfolio continue to generate high SVR rates across multiple HCV patient types,” stated Jay R. Luly, Ph.D., President and Chief Executive Officer. “These results are especially promising for those who have failed previous therapy and for those with more advanced disease.”

The focus of ABT-450 development is to study the compound in combination with other antiviral agents in AbbVie’s portfolio. The three direct acting antivirals, or triple DAA cocktail, studied in the Phase 2b interferon-free Aviator trial included ritonavir-boosted protease inhibitor ABT-450/r, non-nucleoside polymerase inhibitor ABT-333, and NS5A inhibitor ABT-267.

Abstracts for the three presentations can be viewed at the EASL website at www.easl.eu

ABT-450 containing data presentations are as follows:

• Oral Presentation – Kris V. Kowdley, et al., Thursday, April
  25 from 1:30 – 3:30 p.m. CEST
  “Safety and Efficacy of Interferon-Free Regimens of ABT-450/r, ABT-267, ABT-333 ± ribavirin in Patients with Chronic HCV GT1 Infection: Results from the Aviator Study

• Poster # 1190 – Michael Epstein, et al., Saturday,
  April 27 from 12:30 – 1:30 p.m. CEST
  “Study of ABT-267
  2-Day Monotherapy Followed by 12-Week Combination Therapy in Treatment Naïve Patients with Chronic HCV Genotype 1 Infection”

Enanta’s proprietary cyclophilin inhibitor data presentation:

• Poster #1213 – C.M. Owens, et al., Saturday, April 27 from 9:00 a.m. – 6:00 p.m. CEST
  “Cyclophilin Inhibitor EDP-546 is a Potential Cornerstone Drug for Use in Combination with NS5A and Protease Inhibitors Due to Its High Barrier to Resistance”

“We continue to advance our lead cyclophilin candidates in preclinical studies and are continuing to generate and characterize a number of additional candidates,” commented Yat Sun Or, Ph.D., Senior Vice President and Chief Scientific Officer. “We expect to select a preclinical candidate to advance during 2013.”

About Hepatitis C Virus (HCV)

Hepatitis C is a liver disease affecting over 170 million people worldwide. The virus is typically spread through direct contact with the blood of an infected person. Hepatitis C increases a person’s risk of developing chronic liver disease, cirrhosis, liver cancer and death. There is an acute need for new HCV therapies that are safer and more effective for many variants of the virus.

Collaboration with AbbVie (formerly the research-based pharmaceutical business of Abbott Labs)

In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing drug combinations. Under the agreement, AbbVie is responsible for all development and commercialization activities for ABT-450, the program’s lead compound. Enanta received a $57 million upfront payment upon signing the collaboration agreement and is eligible to receive additional pre-commercial milestones, as well as double-digit royalties on any revenue allocable to the collaboration’s protease inhibitors.

Also, for any additional collaborative HCV protease inhibitor product candidate developed under the agreement, Enanta holds an option to fund 40 percent of U.S. development costs and U.S. commercialization efforts(sales and promotion costs) in exchange for 40 percent of any U.S. profits ultimately achieved after regulatory approval.

About Enanta

Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs in the infectious disease field. Enanta is discovering and developing novel inhibitors designed for use against the hepatitis C virus (HCV). These inhibitors include members of the direct acting antiviral (DAA) inhibitor classes – protease (partnered with AbbVie), NS5A (partnered with Novartis) and nucleotide polymerase – as well as a host-targeted
antiviral (HTA) inhibitor class targeted against cyclophilin. Additionally, Enanta has created a new class of antibiotics, called Bicyclolides, for the treatment of multi-drug resistant bacteria, with a current focus on developing an intravenous and oral treatment for hospital and community MRSA (methicillin-resistant Staphylococcus aureus) infections.

Forward Looking Statement

This press release contains forward-looking statements, including with respect to our expectation that we will select a preclinical cyclophilin inhibitor candidate to advance to clinical trials during 2013 and expectations regarding the successful completion of clinical development of ABT-450. Statements that are not historical facts are based on our management’s current expectations, estimates, forecasts and projections about our business and the industry in which we operate and our management’s beliefs and assumptions. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors that may affect actual results include our ability to successfully identify appropriate candidates for clinical development of our future product candidates, the development efforts of our collaborators, regulatory actions affecting clinical development and clinical development of competitive product candidates. Enanta cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this release, and Enanta undertakes no obligation to update or revise these statements, except as may be required by law.

Source: Enanta Pharmaceuticals, Inc.

Investor Contact
Enanta Pharmaceuticals, Inc.
Carol
Miceli, 617-607-0710
cmiceli@enanta.com
or
Media
Contact
MacDougall Biomedical Communications
Kari Watson
or Charles Liles, 781-235-3060
kwatson@macbiocom.com
or cliles@macbiocom.com

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Achillion Presents New Data on ACH-3102 to Treat Hepatitis C at the International Liver Congress

April 23, 2013

- Phase 1 Results Further Demonstrate Potency of ACH-3102 in Genotypes 1a and 1b and Against Resistant HCV-

- Study Shows ACH-3102 and Sovaprevir Can be Co-Administered Without Interaction -

- Total of Six Poster Presentations to be Made During EASL -

AMSTERDAM, The Netherlands, April 23, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN)today announced the presentation of new data demonstrating the efficacy, safety, tolerability, and combinability of ACH-3102, a second-generation, pan-genotypic NS5A inhibitor, at the 48^th Annual Meeting of the European Association for the Study of the Liver (EASL) during the International Liver Congress 2013. ACH-3102 and sovaprevir are currently in Phase II combination development for the treatment of patients with chronic Hepatitis C infection (HCV). During the upcoming poster presentations, data will be reported that demonstrates ACH-3102 achieves a reduction in HCV RNA despite the presence of resistant variants. In addition, ACH-3102 demonstrates no drug-drug interaction with sovaprevir, Achillion's second-generation protease inhibitor.

Data highlights include:

Poster No. 876: A Second Generation NS5A Inhibitor, Demonstrates Potent Antiviral Activity in Patients with Genotype 1A HCV Infection Despite the Presence of Baseline NS5A-Resistant Variants. Friday, April 26, 2013: Poster Session — Category 08c: Viral Hepatitis C: Clinical (therapy).

• Treatment naïve patients with genotype 1 chronic HCV infection, patients received a single dose of ACH-3102 at various doses (Group 1: 50 mg, n=4; 150 mg, n=4; 300 mg, n=4 or placebo, n=2) or placebo and were evaluated for baseline NS5A-resistant viral variants, which was present in the majority of patients. Based on the robust anti-viral effect observed in Group 1, a lower dose (25 mg, n=6) of ACH-3102 or placebo (n=3) was studied in Group 2.
• All tested doses of ACH-3102 were safe and well-tolerated in subjects with chronic HCV Genotype 1 infection.
• Robust, rapid and sustained suppression of plasma HCV RNA levels was observed in all doses (mean reduction of 4.04 log₁₀, 3.78 log₁₀, 3.52 log₁₀, and 3.93 log₁₀ IU/mL for 25 mg, 50 mg, 150 mg and 300 mg doses, respectively, versus reduction of 0.68 log₁₀ IU/mL for placebo). Plasma HCV RNA levels sharply declined within the first two days post-treatment, and remained lower than baseline for at least 14 days.
• ACH-3102 retains potent anti-viral activity against both wild-type and NS5A-resistant viral variants, differentiating it from first-generation NS5A inhibitors.

Poster No. 1201: No Clinically Significant Pharmacokinetic Interaction between Sovaprevir and ACH-3102 in Healthy Volunteers. Saturday, April 27, 2013. Poster Session — Category 08d: Viral Hepatitis C: Clinical (new compounds, resistance).

• In a 24-patient healthy volunteer study, there was no clinically significant pharmacokinetic interaction between ACH-3102 and sovaprevir, Achillion's 2^nd generation NS3 Protease Inhibitor (PI), when co-administered with or without food.
• Co-administration of ACH-3102 and sovaprevir was deemed safe and well-tolerated and the results support a combination Phase 2 study which is currently underway

Poster No. 1199: Findings from Clinical Virology Studies on ACH-3102 are Consistent with Preclinical Observations on its Improved Potency Against Genotype-1A HCV and Resistant Variants. Saturday, April 27, 2013: Poster Session — Category 08d: Viral Hepatitis C: Clinical (new compounds, resistance).

• Single doses of ACH-3102 at 25 mg - 300 mg have previously shown robust antiviral activity in Genotype 1a patients, with reductions in HCV RNA observed in presence of baseline mutations associated with viral resistance to NS5A inhibitors.
• These results show that ACH-3102 administered in 50 mg, 150 mg, and 300 mg doses reduced viral load by 3.98-4.60 log₁₀ IU/mL in four patients with Y93C/D/H mutation, 3.35-4.02 log₁₀ IU/mL in four patients with M28T/V mutation, and 3.40 log₁₀ IU/mL in one patient with L31M mutation.
• Also in GT-1a patients, a comparison of 1-150 NS5A versus full-length NS5A showed less than five-fold differences in their susceptibility to ACH-3102, compared with up to a greater than 358-fold differences in susceptibility to daclatasvir.
• ACH-3102 retained potency (EC₅₀0.042 nM) in GT-1b patients with pooled NS5A mutations, all of whom carried the L31M and Y93H double mutation. In contrast, daclatasvir potency was reduced 2,200-fold (EC₅₀ 22 nM).

"The high barrier to resistance observed with ACH-3102 to date continues to confirm our view that ACH-3102 is unique from other NS5As and has the promise to be a cornerstone therapy in the treatment of Hepatitis C," said Milind Deshpande, Ph.D., President of Research and Development and Chief Scientific Officer of Achillion. "The unique characteristics of ACH-3102, combined with the unique profile of our 2nd generation PI, sovaprevir, which also has a higher barrier to resistance than typical PIs, make for what we believe is a high potential combo, competitive against both current and emerging combinations."

Additional Poster Presentations at EASL:

Friday, April 26, 2013: Poster Session — Category 08c: Viral Hepatitis C: Clinical (therapy).

• Lawitz E., et al. ACH-2684 Demonstrates Potent Viral Suppression in Genotype 1 Hepatitis C Patients with and without Cirrhosis: Safety, Pharmacokinetic, and Viral Kinetic Analysis. Pres. #847.
• Agarwal A., et al. Viral Kinetics Modeling to Predict cEVR and Aid in Dose Selection Decisions for Phase 2/3 Clinical Trials. Pres. #784.

Saturday, April 27, 2013: Poster Session — Category 08d: Viral Hepatitis C: Clinical (new compounds, resistance).

• Fabrycki J., et al. Findings from Clinical Virology Studies on Sovaprevir, a Phase 2 HCV NS3A Protease Inhibitor, Indicate a High Pharmacological Barrier to Viral Resistance. Pres. #1200.

About ACH-3102

The NS5A protein is a clinically validated target that serves multiple functions at various stages of the HCV life cycle including involvement in virion production, interaction with host proteins and association with interferon-resistance. ACH-3102, Achillion's second generation NS5A inhibitor, has demonstrated potent activity against all HCV genotypes in vitro and in preclinical studies achieved additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, interferon and ribavirin. In preclinical studies, ACH-3102 demonstrated excellent potency, in the pico-molar range, against wild type HCV RNA replication, as well as potency against resistant mutants that have been identified in clinical studies. ACH-3102 was deemed to be safe and well-tolerated in Phase 1 development and achieved mean maximal reductions in HCV RNA of 3.78 log₁₀ after a single dose. ACH-3102 has been granted fast track designation by the FDA and is currently being evaluated in Phase 2 for the treatment of HCV.

About Sovaprevir

Sovaprevir, previously referred to as ACH-1625, is a pan-genotypic HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. Sovaprevir is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, sovaprevir demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. Sovaprevir has rapid and extensive partitioning to the liver, as well as high liver/plasma ratios, and 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. Sovaprevir is currently in Phase 2 clinical development and has shown clinical antiviral activity against genotypes 1 and 3. Fast Track status was granted to sovaprevir 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 more than 5 million people in the United States, making HCV more than twice as widespread as HIV. Three-fourths of the global 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 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 expected potency, safety, tolerability, effectiveness, combinability and other characteristics of sovaprevir and ACH-3102; and Achillion's expectations regarding timing for the commencement, completion and reporting of results of its clinical trials of both ACH-3102 in combination with ribavirin and sovaprevir in combination with ACH-3102. We may use words such as "expect," "anticipate," "project," "intend," "plan," "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: replicate in later clinical trials positive results found in earlier stage clinical trials of sovaprevir, ACH-3102 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; 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, 2012 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.

Source

Achillion Announces Updated Phase 2 Results Including Early Sustained Virologic Response on ACH-3102 Plus Ribavirin in Genotype 1b Treatment-Naive Hepatitis C Patients

April 23, 2013

- ACH-3102 deemed safe and well-tolerated following 12 weeks of therapy -
- High barrier to resistance demonstrated with no on-treatment virologic breakthrough observed -
- Novel NS5A inhibitor study supports differentiated profile of ACH-3102 -

NEW HAVEN, Conn., April 23, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced updated interim safety and efficacy results, including early sustained virologic response (SVR4) data, from the pilot Phase 2 trial evaluating once-daily ACH-3102 plus ribavirin (RBV) in treatment-naïve patients with genotype 1b, IL28B CC subtype, chronic hepatitis C virus (HCV) infection. All of the 8 patients enrolled in the trial completed 12 weeks of treatment with no virologic breakthrough observed. ACH-3102 also demonstrated continued declines in HCV RNA in the presence of up to six baseline mutations that are known to confer a high level of resistance to 1^st generations NS5A inhibitors. ACH-3102 was deemed safe and well-tolerated with no significant adverse events reported. In all, 75% of patients (6 of 8) had HCV RNA < 25 IU/ml at the end of treatment and 63% (5 of 8) achieved early sustained virologic response 4 weeks (SVR4) after the completion of therapy.

Dr. Andrew Muir, Principal Investigator and Assistant Professor of Medicine and Director of Gastroenterology/Hepatology Research at Duke Clinical Research Institute commented, "The preliminary results from this novel study of a single DAA, an NS5A inhibitor, plus ribavirin demonstrates the safety, high barrier to resistance, and preliminary efficacy of ACH-3102. The profound activity of ACH-3102 as a single DAA, along with its safety profile and lack of virologic breakthrough to date makes this a very promising compound to study further in combination with other oral agents, including sovaprevir, for the treatment of HCV."

Overall, ACH-3102 was well-tolerated and demonstrated a safety profile consistent with that seen during Phase 1 trials in both healthy subjects and HCV-infected patients. No patients experienced virologic breakthrough while on treatment and no patients discontinued treatment due to an adverse event. Final study results are expected to be submitted for presentation at a medical conference later this year.

	Virologic End Points
Total 8 subjects enrolled	RVR	ETR	SVR4
	n = 8	n = 8	n = 8
# of subjects	6 / 8	6 / 8*	5 / 8 **
(%)	(75%)	(75%)	(63%)
RVR = Rapid Virologic Response, HCV RNA < LLOQ ( < 25 IU/mL) at week 4 of treatment
ETR = End of Treatment Response, HCV RNA < LLOQ ( < 25 IU/mL) at week 12 of treatment
* The 2 patients who did not achieve ETR were started on pegylated interferon, ribavirin and telaprevir at the end of the 12-week treatment period, and demonstrated undetectable viral levels beginning at week 13.
** 1 patient with virologic relapse at week 15.

"We believe that these interim results further strengthen our position that ACH-3102 is a differentiated NS5A inhibitor possessing attributes that make it a true second-generation compound," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "The safety and efficacy profile support our recently initiated Phase 2 -007 trial evaluating 12 weeks of our protease inhibitor, sovaprevir, in combination with ACH-3012 for the treatment of genotype 1 HCV. With that study now underway, we look forward to reporting interim results beginning in the third quarter of this year, and will continue to explore and execute opportunities to combine our agents with other compounds that could further shorten the treatment duration or provide additional flexibility for treatment regimens to broadly cure HCV."

About ACH-3102

The NS5A protein is a clinically validated target that serves multiple functions at various stages of the HCV life cycle including involvement in virion production, interaction with host proteins and association with interferon-resistance. ACH-3102, Achillion's second generation NS5A inhibitor, has demonstrated potent activity against all HCV genotypes in vitro and in preclinical studies achieved additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, interferon and ribavirin. In preclinical studies, ACH-3102 demonstrated excellent potency, in the pico-molar range, against wild type HCV RNA replication, as well as potency against resistant mutants that have been identified in clinical studies. ACH-3102 was deemed to be safe and well-tolerated in Phase 1 development and achieved mean maximal reductions in HCV RNA of 3.78 log₁₀ after a single dose. ACH-3102 has been granted fast track designation by the FDA and is currently being evaluated in Phase 2 for the treatment of 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 more than 5 million people in the United States, making HCV more than twice as widespread as HIV. Three-fourths of the global 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 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 expected potency, safety, tolerability, effectiveness and other characteristics of sovaprevir and ACH-3102; and Achillion's expectations regarding timing for the commencement, completion and reporting of results of its clinical trials of both ACH-3102 in combination with ribavirin and sovaprevir in combination with ACH-3102. We may use words such as "expect," "anticipate," "project," "intend," "plan," "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: replicate in later clinical trials positive results found in earlier stage clinical trials of sovaprevir, ACH-3102 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; 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, 2012 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.

Source