R&D Highlights

Alnylam announces today updates to the statistical analysis plan for the HELIOS-B Phase 3 study of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy. These will include updates to the primary and secondary endpoint structure, as well as study exposure. Topline results are expected to be available in late June or early July. Details will be discussed on the conference call this morning.

Published results from Phase 3 APOLLO-B study of patisiran in the New England Journal of Medicine.

Presented positive initial Phase 1 results with ALN-TTRsc04 demonstrating rapid knockdown achieved by a single dose with mean serum TTR reduction up to 97%, with durability supporting potential for annual dosing and an encouraging safety profile.

Presented positive results from the KARDIA-1 Phase 2 dose-ranging study of zilebesiran, an investigational RNAi therapeutic in development to treat hypertension patients at high cardiovascular risk, during the American Heart Association (AHA) Scientific Sessions.

Announces today that the U.S. Food and Drug Administration (FDA) has provided clearance to initiate the multiple-dose part (Part B) of the ongoing Phase 1 study of ALN-APP, an investigational RNAi therapeutic targeting amyloid precursor protein (APP) in development for the treatment of Alzheimer's disease and cerebral amyloid angiopathy. The FDA has confirmed that multiple-dosing in the Phase 1 study may proceed at doses up to 180 mg given every six months, which covers all dose regimens planned to be explored in Part B. A partial clinical hold remains for higher or more frequent dosing regimens.

• Reported updated positive interim results for the ongoing single ascending dose portion of the Phase 1 study of ALN-APP in patients with early-onset Alzheimer's disease at the 2023 Alzheimer's Association International Conference and at the 16th Clinical Trials in Alzheimer's Disease conference.

Presented positive initial Phase 1 results with ALN-KHK demonstrating robust target engagement and an encouraging safety profile, supporting continued development as a novel treatment for type 2 diabetes mellitus.

Filed an Investigational New Drug (IND) application for ALN-BCAT, an investigational RNAi therapeutic targeting β-catenin in development for the treatment of hepatocellular carcinoma.

Sanofi presented positive results from the ATLAS-OLE Phase 3 extension study of fitusiran, demonstrating a substantially improved safety profile and consistent bleed protection in people with hemophilia A or B, with or without inhibitors. Specifically, the risk of thrombosis was reduced, with rates comparable to those reported in the general hemophilia population.

• Sanofi expects to submit a New Drug Application (NDA) to the FDA in 2024.