Alnylam Pharmaceuticals, based in Cambridge, MA, has announced that it has initiated a Phase 1 study of ALN-AT3, an investigational therapy for the treatment of hemophilia and rare bleeding disorders.
The company is developing ALN-AT3, a subcutaneously administered (injection just under the skin) RNAi therapy that targets antithrombin (AT) as a way to treat hemophilia A or B, hemophilia A or B with inhibitors, and other rare bleeding disorders. AT is a small plasma protein molecule produced in the liver that inactivates factor Xa and thrombin, which are needed for blood clotting. It plays a key role in normal hemostasis.
ALN-AT3 incorporates Alnylam’s proprietary gene-silencing technology called RNA interference or RNAi. Discovered by scientists in the late 1990s, RNAi is a natural process in which cells turn off, or silence, the activity of specific genes. ALN-AT3 silences certain genes associated with AT generation, “switching off” the protein’s production.
The Phase 1 study will be conducted in the United Kingdom as a single- and multi-dose, dose-escalation study consisting of two parts. Part A will be a randomized, single-dose escalation study, enrolling up to 24 healthy volunteer subjects. It will evaluate the safety and tolerability of a single low dose of ALN-AT3, with the potential to show changes in AT plasma levels at sub-pharmacologic doses. Part B of the study will be an open-label, multi-dose escalation study enrolling up to 18 people with moderate to severe hemophilia A or B. It will evaluate the safety and tolerability of multiple doses of subcutaneously administered ALN-AT3 in hemophilia subjects.
“The unmet need for new therapeutic options to treat people with hemophilia remains very high, particularly in those patients that develop inhibitory antibodies to their replacement factor. Indeed, availability of a safe and effective subcutaneously administered therapeutic with a long duration of action would represent a marked improvement over currently available approaches for prophylaxis,” said Claude Negrier, MD, head of the Hematology Department and director of the Haemophilia Comprehensive Care Centre at Edouard Herriot University Hospital in Lyon, France “I look forward to the continued advancement of this innovative therapeutic candidate in clinical studies.”
Source: Alnylam press release dated January 22, 2014
