Loading ...

Editor's note: This story has been updated from the previous version.

The US Food and Drug Administration (FDA) has approved fitusiran (Qfitlia, Sanofi) for bleeding prophylaxis in patients aged 12 years or older with hemophilia A and B with or without factor VIII or IX inhibitors.

Fitusiran is a first-in-class small interfering RNA therapeutic that reduces antithrombin production in the liver by downgrading antithrombin gene expression, leading to an increase in thrombin, an enzyme critical for blood clotting.

The approval of fitusiran “is significant for patients with hemophilia because it can be administered less frequently than other existing options,” just once subcutaneously every 2 months, said Tanya Wroblewski, MD, an FDA deputy director, in an agency press release.

Approval was based on several trials in Sanofi’s ATLAS development program. The initial 80-mg monthly dose was abandoned in favor of bimonthly dosing based on antithrombin levels after the fixed dose caused excessive clotting in some patients.

Studies using adjustable dosing found a 71% reduction in the annualized bleeding rate (ABR) among patients without inhibitors treated with fitusiran prophylaxis instead of on-demand clotting factor concentrates (mean ABR, 9.0 vs 31.4) and a 73% reduction in the ABR among patients with inhibitors treated with fitusiran instead of on-demand bypassing agents (mean ABR, 5.1 vs 19.1), according to a Sanofi press release.

During an open-label extension study, the median observed ABR with fitusiran prophylaxis was 3.8 in patients without inhibitors and 1.9 in those with inhibitors.

Viral infection, nasopharyngitis, and bacterial infection were the most common adverse events.

Fitusiran labeling contains a boxed warning of both thrombotic events and gallbladder disease, including the risk for cholecystectomy. There’s also a warning for liver toxicity and the need to monitor liver tests at baseline and then monthly for at least 6 months after starting treatment or a dose increase.

The initial starting dose is 50 mg subcutaneous every 2 months, with dosage and frequency adjusted as needed to maintain antithrombin activity levels between 15% and 35% of normal using the Innovance Antithrombin assay (Siemens), which has been cleared by FDA for the purpose.

Fitusiran’s average annual wholesale acquisition cost will be $642,000, according to multiple news reports.

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 Medical News. Alex is also an MIT Knight Science Journalism fellow. Email:  aotto@mdedge.com