Vertex Pharmaceuticals Incorporated, a company discovers, develops and commercializes innovative therapies, and its collaborator Alios BioPharma, Inc., a biotechnology company developing novel medicines aimed for viral diseases, have reported positive results from a viral kinetic study of the nucleotide analogue ALS-2200 for the treatment of hepatitis C.

There was a median 4.54 log10 reduction in hepatitis C virus (HCV) RNA in people with genotype 1 chronic hepatitis C who were new to treatment (n=8) after seven days of dosing with 200 mg of ALS-2200 once daily. ALS-2200 was well-tolerated in this study, and no patients discontinued due to adverse events. Based on these data, Vertex plans to begin phase II studies this year of 12-week all-oral regimens including ALS-2200 in people with genotype 1 hepatitis C, pending discussions with regulatory agencies.

Patients with hepatitis C dosed with ALS-2200 in this study had a dose-dependent, consistent and rapid decline in HCV RNA. After three days of dosing, a median 3.85 log10 decline was observed among patients in the 200 mg dose group. In this dose group, a median 4.54 log10 decline was observed after seven days of dosing, which was maintained for up to two days after the completion of dosing. Four of eight patients in this dose group achieved HCV RNA levels below the limit of quantification ( < LOQ = < 25 IU/mL). There were no serious adverse events observed in people dosed with ALS-2200 in the study. Data from this study have been submitted to a medical meeting for presentation in the second half of this year.

Based on these data, Vertex expects to conduct a study to evaluate ALS-2200 in combination with Incivek (telaprevir), the company's approved protease inhibitor for people with genotype 1 hepatitis C, and a study of ALS-2200 in combination with ribavirin. 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 hepatitis C.

"We're encouraged by the substantial, rapid and consistent viral decline and initial safety results from this study, which make ALS-2200 a very promising part of Vertex's hepatitis C pipeline," said Robert Kauffman, MD, PhD, senior vice president and chief medical officer at Vertex. "ALS-2200, with its high level of antiviral activity, gives us flexibility to explore several combinations of all-oral treatment regimens for hepatitis C. We're moving quickly to begin the first Phase 2 trials this year."

"The rapid advancement of ALS-2200 through this first viral kinetic study underscores the strength of our collaboration with Vertex and our shared commitment to develop new medicines for hepatitis C," said Lawrence M Blatt, PhD, founder, president and CEO of Alios BioPharma. "We look forward to continued collaboration with Vertex and to the start of multiple phase II studies of ALS-2200 later this year."

This double-blind, placebo-controlled, phase I trial was designed to evaluate the safety and tolerability of single ascending doses of ALS-2200 in healthy volunteers and of multiple ascending doses in people with genotype 1 chronic hepatitis C. A secondary objective was to evaluate the effects on viral kinetics of ALS-2200 during seven days of dosing in people with hepatitis C. The first part of the trial enrolled healthy volunteers to evaluate pharmacokinetics of single ascending doses of ALS-2200. The second part of the study enrolled people with hepatitis C to evaluate the antiviral activity of multiple ascending doses of ALS-2200. Of the patients with hepatitis C in the ALS-2200 treatment groups, two were genotype 1a, 29 were genotype 1b and one patient's genotype 1 subtype was not able to be determined.

Vertex and Alios are also conducting a phase I seven-day viral kinetic study of a second nucleotide analogue, ALS-2158. Data from this study are expected in the next few months.

ALS-2200 and ALS-2158 are nucleotide analogues that appear to have a high barrier to drug resistance based on in vitro studies. Both compounds are designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Each compound is structurally distinct (adenosine and uridine) and has a different mechanism of action. In vitro studies of both compounds 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 and ALS-2158 through an exclusive worldwide 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 programme.

Incivek (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 US 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 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.