Alnylam adds two RNAi programs to its hepatitis pipeline

Alnylam ($ALNY) this week announced the addition of RNA interference therapies for the hepatitis delta virus and chronic liver infections to its clinical pipeline at the American Association for the Study of Liver Diseases meeting in Boston. The company also said it remains on track to select a candidate for its hepatitis B program by the end of the year and hopes to file an investigational new drug application with the FDA in late 2015.

Alnylam is the market leader in RNAi-based therapies. RNAi accomplishes gene silencing using novel drug delivery techniques involving small interfering RNA (or siRNA) by cleaving messenger RNA within cells' cytoplasm, preventing gene transcription from taking place. The naturally occurring paradigm's discovery in 1998 earned scientists Andrew Fire and Craig Mello a Nobel Prize in 2006.

"We believe that multiple opportunities exist for RNAi therapeutics for hepatic infectious diseases, and our initial focus on HBV will now be expanded to include programs for HDV and liver-specific immune checkpoint blockade by targeting hepatocyte-expressed PD-L1. In both cases, our approach will employ our Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, enabling subcutaneous dose administration with high potency and long durability, and a wide therapeutic index," said Alnylam vice president and entrepreneur-in-residence Laura Sepp-Lorenzino in a statement.

HDV is an RNA-based virus that is acquired concurrently with or subsequently to HBV and afflicts 15 to 20 million people an year. The disease exacerbates HBV in patients with both viruses, Alnylam says, or about 5% of the 400 million people with that disease.

"Since no effective antiviral therapy is currently available for treatment of type D hepatitis, liver transplantation may be considered for cases of fulminant acute and end-stage chronic hepatitis D," adds the World Health Organization website.

The other new addition to its pipeline targets the surface protein receptor PD-L1. It is over-expressed during HBV and hepatitis C infections, potentially weakening the body's immune response to the conditions, Alnylam says.

Meanwhile the more advanced HBV program aims to decrease the expression of tolerogenic hepatitis surface antigen, according to the the release. At the May 12-15 TIDES meeting of oligonucleotide and peptide professionals in Providence, RI, the company released data from its preclinical research on chronically infected chimpanzees showing significant decreases in viral HBV DNA levels.

With the exception of hepatitis B, the company is focusing on rare diseases, with a focus on the liver, the organ that is most amenable to RNAi delivery. But Chief Business Officer Laurence Reid said in October that the company is also looking to enter bigger markets via partnerships.

Also this week, fellow RNAi specialist Arrowhead ($ARWR) released new data from the Phase IIa study of its hepatitis B treatment, which showed a reduction of the disease's surface antigens.

There are no commercially available RNAi therapies yet, but market research firm Allied Market Research forecasts that RNA-based therapies will generate $1.2 billion in revenue by 2020, a compounded annual growth rate of 28.4%.

- read the release