Fitusiran Approved for Hemophilia A, B

The US Food and Drug Administration has approved fitusiran for bleeding prophylaxis in hemophilia A and B with or without inhibitors.

Fitusiran is a first-in-class small interfering RNA therapeutic that reduces antithrombin production in the liver by downgrading antithrombin gene expression. Antithrombin is a protein that inhibits clot formation. 

The agent “has the potential to enable prophylaxis for people around the world living with hemophilia A or B with or without inhibitors by virtue of its low overall treatment burden, with as few as six small-volume subcutaneous injections per year that do not require refrigeration,” Sanofi said in a press release. 

Approval was based on several trials in the company’s ATLAS development program. 

In one trial, ATLAS-INH, 57 men with severe hemophilia A or B with inhibitors were randomized 2:1 to 80 mg fitusiran once monthly or to continue with on demand bypassing agents for 9 months. There was a 91% drop in the mean annualized bleeding rate with fitusiran, from 18.1 events in the on-demand group to 1.7 events. There were no treated bleeding events in two-thirds of fitusiran patents vs just 5% of patients in the on-demand group. 

A similar trial, ATLAS-A/B, included 120 male subjects with severe hemophilia A or B but without inhibitors. They were randomized 2:1 to either fitusiran 80 mg monthly or to continue with on-demand clotting factor concentrates, again for 9 months. The mean annualized bleeding rate was 3.1 events with fitusiran vs 31 events with continued clotting factors. There were no treated bleeding events in half of fitusiran subjects vs just 5% of patients in the on-demand group. 

Increased alanine aminotransferase was the most common adverse event with fitusiran, occurring in up to 32% of subjects. Less common side effects included cholelithiasis, cholecystitis, and thrombotic events. 

To minimize such risks, dosing is based on antithrombin levels instead of the 80 mg regimen used in the trials; the goal is to maintain antithrombin activity levels between 15%-30% of normal. 

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]