FDA approves Alhemo for hemophilia bleeding prevention

Alhemo is a tissue factor pathway inhibitor (TFPI) antagonist that is dosed in a prefilled, premixed pen for subcutaneous injection (60 mg/1.5 mL, 150 mg/1.5 mL, or 300 mg/3 mL) via a thin 32 gauge, 4 mm needle, which is provided separately. Currently, many treatments for hemophilia A or B with inhibitors are administered via intravenous infusions, and Alhemo is the first subcutaneous injection treatment of its kind for this population.

Alhemo is designed to block a protein called TFPI in the body that stops blood from clotting. By blocking TFPI, Alhemo improves the production of thrombin, a protein that helps to clot the blood and prevent bleeding, when the other clotting factors are missing or deficient in the presence of inhibitors.

An estimated 30% of patients living with severe hemophilia A and 5-10% of those with severe hemophilia B develop inhibitors, which makes treatment of hemophilia in some patients significantly more challenging. While treatments have improved the lives of many living with hemophilia, those with hemophilia B with inhibitors still experience a disease and treatment burden due to limited prophylactic treatment options to prevent bleeding. Because of the unmet medical needs in this population, and based on the Phase II clinical trial results, the FDA granted Breakthrough Therapy designation for Alhemo in hemophilia B with inhibitors. 

The primary objective from the pivotal Phase III explorer7 study compared the number of treated spontaneous and traumatic bleeding episodes, as measured by annual bleeding rate (ABR), showed an 86% reduction of ABR in patients randomized to receive Alhemo prophylaxis compared to no prophylaxis (ABR ratio of 0.14, 95% confidence interval [CI], 0.07 to 0.29, p-value <0.001). The estimated mean ABR was 1.7 for patients on Alhemo  prophylaxis compared to 11.8 for patients with no prophylaxis and the overall median ABR was zero for treated spontaneous and traumatic bleeds compared with 9.8 ABR in patients with no prophylaxis.  As a supportive secondary efficacy endpoint, 64% of the patients randomized to receive Alhemo  prophylaxis treatment experienced zero treated spontaneous and traumatic bleeds during the first 24 weeks of treatment vs. 11% with no prophylaxis.  In the explorer7 study, the most common adverse reactions reported in ≥5% of patients randomized to receive Alhemo  were injection site reactions (18%) and urticaria (6%). Serious adverse reactions were renal infarct and hypersensitivity reaction.

"The development of inhibitors remains the most serious treatment-related complication for people living with hemophilia. For patients with inhibitors, especially in hemophilia B, their hemophilia may remain poorly controlled and pose a life-threatening risk," said Amy Shapiro, MD, CEO and co-medical director at the Indiana Hemophilia & Thrombosis Center, Inc. "The approval of Alhemo – a first-of-its-kind, prophylaxis, subcutaneous injection pen for adults and children 12 years and older with hemophilia A and B with inhibitors – provides a much-needed alternative to the current standard of care in hemophilia B with inhibitors, while offering patients with hemophilia A with inhibitors more treatment options, ultimately providing more patients with inhibitors the opportunity to personalize their care and address current treatment gaps."

In addition to the U.S., Alhemo is currently approved in Australia, Japan, Switzerland and the EU, with specific indications varying by country.