UPDATED: Alnylam's hepatitis B therapy shows promise in animal studies

RNAi specialist Alnylam ($ALNY) is adding a hepatitis B virus therapy to its pipeline of candidates that employ its enhanced stabilization chemistry-GalNAc-conjugate technology enabling subcutaneous dosing and plans to file an IND by the end of 2015.

GalNAc-siRNA conjugates are Alnylam's proprietary delivery platform that target liver hepatocyte cells for the delivery of RNA interference-based therapy via the asialoglycoprotein receptor. GalNAc is a sugar molecule that facilitates binding and uptake of the conjugated siRNA molecule by the hepatocytes. Alnylam focuses on the liver because that is where RNAi delivery is optimized.

Alnylam COO Barry Greene

"The siRNA gets basically chewed up when not protected," said Alnylam COO Barry Greene. It is the active ingredient and cleaves messenger RNA to silence gene expression. 

"We've now blocked the degradation of siRNA at the right spot and in the process of doing that we've improved the potency and durability," Greene said, adding that the enhanced stabilization chemistry technology is used in the company's other candidates as well, such as ALN-AT3 for the treatment of hemophilia and rare bleeding disorders.

Substantiating its IND timeline, the company released data from its preclinical research on chronically infected chimpanzees showing significant decreases in viral HBV DNA levels. It is presenting the data at the May 12-15 TIDES meeting of oligonucleotide and peptide professionals in Providence, RI.

"We are very encouraged by the data we are presenting for the first time today, which we believe constitute the most robust proof-of-concept preclinical data to date with an RNAi therapeutic for the treatment of HBV," said Alnylam Vice President Laura Sepp-Lorenzino, the project leader of the HBV program, in a statement. "We believe our ALN-HBV RNAi therapeutic represents a powerful mechanism for inhibiting all steps of the HBV life cycle: replication, assembly, secretion of virus and secretion of sub-viral antigens."

Worldwide, 400 million people suffer from chronic hepatitis B, according to Alnylam, which says the disease claims 1 million people annually. Moreover, the company says the cure rate using current therapies is less than 10%.

Alnylam acquired the HBV program from its January 2014 acquisition of Merck's ($MRK) RNAi assets, including its Sirna Therapeutics subsidiary, for $175 million plus milestone payments. Along with Merck, Novartis ($NVS) exited the arena this year, making investors nervous about RNAi products' prospects in general; they pushed Alnylam's stock price down 20% on the Novartis news.

Alnylam COO Barry Greene defended the company aggressively in an April interview with FierceDrugDelivery, saying Big Pharma has "never been able to innovate." Who's right? The verdict won't be delivered until at least 2017, when Alnylam's first product for the treatment of an orphan indication could hit the market if all goes as planned.

- read the release