Alnylam prepares for U.K. Phase I and plans for the future

Alnylam Pharmaceuticals ($ALNY) is preparing to move ALN-TTRsc, its lead product using the GalNAc-siRNA delivery system, into clinical trials. This will begin with a Phase I study in the U.K., where the subcutaneous RNAi therapeutic will be assessed in up to 40 healthy volunteers.

ALN-TTRsc is in development for the treatment of transthyretin (TTR)-mediated amyloidosis (ATTR) and is delivered to liver cells through uptake by the asialoglycoprotein receptor. It works by rapid and sustained knockout of the mutant TTR protein. The trial will focus on safety and tolerability, but will also look at the serum TTR levels to get first hints of any clinical activity, and should begin early this year, provided the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) approves the clinical trial application (CTA). Data is expected midyear.

"This CTA filing for ALN-TTRsc marks our first for an RNAi therapeutic that utilizes our proprietary GalNAc conjugate delivery platform enabling subcutaneous dose administration," says Akshay Vaishnaw, executive vice president and chief medical officer at Alnylam.

Providing the results are positive, Alnylam plans to follow the Phase I trial up with a Phase II study in ATTR patients with familial amyloidotic cardiomyopathy (FAC), planned for late this year, and a Phase III trial in 2014.

Alnylam has a busy couple of years planned through 2014 as it moves forward its "Alnylam 5x15" product strategy. This aims to have 5 programs in clinical development by the end of 2015.

Still in the TTR arena, the company plans to start a pivotal Phase III trial of its intravenous ATTR RNAi therapeutic, ALN-TTR02 by late this year. This therapeutic is currently in a Phase II trial to assess the safety and tolerability of multiple doses, and data is expected midyear. This will be followed by an open-label extension study. Alnylam will market ALN-TTR02 worldwide outside Japan and other Asian countries, where it has a deal with Genzyme.

Alnylam has added the RNAi therapeutic ALN-AT3 to the "5x15" clinical pipeline. It plans to begin Phase I late this year, with data due next year. This treatment for hemophilia and other rare bleeding disorders targets antithrombin, and also uses the GalNAc-conjugate delivery system.

The RNAi therapeutic ALN-AS1 program, which targets aminolevulinate synthase 1 (ALAS-1) and is in development to treat the rare genetic disorder acute intermittent porphyria, has also been added to the "5x15" project. Alnylam plans to select a lead GalNAc conjugate by late this year and begin clinical trials next year.

- read the press release on Alnylam's 2012/2013 plans
- see the press release on the clinical trial application