Sirna says it will advance Sirna-AV34 to clinical testing for hepatitis C

By E. Janene Geiss

Philadelphia, Dec. 21 - Sirna Therapeutics, Inc. said Wednesday that it has selected Sirna-AV34, a systemically delivered, chemically modified short interfering RNA (siRNA) compound as its candidate for advancement to human clinical testing against hepatitis C virus.

Sirna said it completed its preclinical evaluation of the efficacy of Sirna-AV34 and has begun cGMP manufacturing for its phase 1 clinical studies, according to a company news release.

Sirna said it expects to start IND-enabling toxicology studies in the first quarter of 2006 followed by the filing of an Investigational New Drug Application with the Food and Drug Administration by the fourth quarter of 2006.

Sirna-AV34 is a systemically delivered, nanoparticle-based therapeutic targeting the hepatitis C virus, officials said.

The compound consists of multiple individual, chemically modified, siRNA sequences that target highly conserved sequences in the hepatitis C viral genome.

Sirna-AV34 is designed to inhibit viral replication and dramatically reduce the selection of drug resistant mutant variants. The design principles used in Sirna-AV34 were validated by demonstrating reduction in escape mutation frequency in the hepatitis C virus sub-genomic replicon system in vitro.

No existing therapeutic approach has the potential to broadly inhibit hepatitis C viral replication while reducing the probability of drug resistant variants, officials said.

"The selection of Sirna-AV34 as our clinical candidate reflects two major accomplishments of our research team. The first is the design, chemical modification and synthesis of a stable and potent siRNA compound, which is effective broadly against the hepatitis C virus. The second is the development of a proprietary nanoparticle delivery technology capable of efficient and specific delivery of the siRNA compound to hepatocytes. These two achievements have provided us with a unique opportunity to bring this groundbreaking therapy to the clinic," senior vice president and chief scientific officer Barry Polisky said in the release.

Sirna said it has completed its preclinical evaluation including demonstration of systemic efficacy in both rodent and primate animals.

As previously reported in a rodent with hepatitis B virus used as a surrogate for hepatitis C virus, Sirna demonstrated that a chemically optimized and encapsulated siRNA had significant antiviral activity and prolonged duration of effect in vivo, officials said.

Recent data from a primate with hepatitis C replication demonstrated that Sirna's systemically delivered siRNA compound dramatically suppressed hepatitis C viral titers via an RNA interference mechanism, officials said.

Sirna-AV34 will be manufactured at Sirna's cGMP facilities in Boulder, Colo., for both phase 1 enabling toxicology studies and phase 1 human clinical testing.

Sirna is a San Francisco clinical-stage biotechnology company developing RNAi-based therapies for age-related macular degeneration, hepatitis B and C, dermatology, asthma, Huntington's disease, diabetes and oncology.

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