The FDA has approved fitusiran (Qfitlia) for routine prophylaxis to prevent or reduce bleeding episodes in adult and pediatric patients aged 12 years or older with hemophilia A or B, with or without factor VIII or IX inhibitors (neutralizing antibodies). Qfitlia is administered subcutaneously, starting once every two months.

Qfitlia (fitusiran) reduced annualized bleeding rates by 73% in patients with inhibitors and by 71% in those without inhibitors when using an antithrombin-guided dosing regimen. These results were observed in patients with hemophilia A or B enrolled in long-term extension studies after randomized clinical trials.

Hemophilia A and B are inherited bleeding disorders resulting from dysfunction or insufficient levels of clotting factor VIII or IX, respectively. Patients are at increased risk for spontaneous or prolonged bleeding events, which are commonly managed through episodic or prophylactic replacement therapy with factor products or bypassing agents. Qfitlia, a small interfering RNA therapy, does not replace clotting factor but reduces hepatic production of antithrombin, thereby increasing thrombin generation to enhance hemostasis.

Dosing and frequency are adjusted based on antithrombin activity, monitored via the INNOVANCE Antithrombin test (Siemens Healthcare Diagnostics GmbH), which received FDA clearance as a companion diagnostic. This test is used to monitor and inform dosing and frequency to achieve antithrombin activity in the target range, reducing bleeding and the risk of excessive blood clotting. The approved regimen uses an adjustable, antithrombin-guided dosing strategy.

Efficacy and safety were evaluated in two multicenter, randomized clinical trials enrolling 177 adult and pediatric male patients with hemophilia A or B. One trial enrolled patients with inhibitors previously treated with bypassing agents; the other enrolled patients without inhibitors treated with clotting factor concentrates. Participants initially received either fixed monthly doses of fitusiran or on-demand treatment for nine months. Due to thrombotic risk, the fixed-dose regimen was not approved. All participants subsequently entered a long-term extension study with antithrombin-based dosing.

Qfitlia carries a boxed warning for thrombotic events and gallbladder disease, including cases of cholecystectomy. Hepatotoxicity has also been reported, warranting liver function monitoring at baseline and monthly for at least six months after initiation or dose escalation. The most common side effects include viral infections, nasopharyngitis, and bacterial infections.

The FDA granted Qfitlia both Orphan Drug and Fast Track designations.

Reference:
U.S. Food and Drug Administration. FDA approves novel treatment for hemophilia A or B, with or without factor inhibitors: medication can be given up to once every 2 months [news release].