Novo Nordisk bleeding disorder injection gets USFDA nod
Plainsboro: Novo Nordisk has announced that the U.S. Food and Drug Administration (FDA) has approved Alhemo (concizumab-mtci) injection as a once-daily prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A or B with inhibitors. 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 a 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 2 clinical trial results, the FDA granted Breakthrough Therapy designation for Alhemo in hemophilia B with inhibitors.
Hemophilia is a rare bleeding disorder that affects approximately 800,000 people worldwide and 32,000 people in the US, that impairs the body's ability to make blood clots, a process needed to stop bleeding. It is caused by a mutation in a gene that provides instructions for making the clotting factor proteins needed to form a blood clot. This change can prevent the clotting protein from working properly or be missing altogether. There are different types of hemophilia, which are characterized by the type of clotting factor protein that is defective or missing. Hemophilia A is caused by low levels of clotting factor VIII (FVIII), while hemophilia B is caused by low levels of clotting factor IX (FIX). Hemophilia is often treated by replacing the missing clotting factor via intravenous infusions, also known as replacement therapy. However, sometimes the body can produce inhibitors as an immune response to the clotting factors in the therapy, which means replacement therapy does not work and limits overall treatment options.
"The approval of Alhemo signifies a remarkable achievement in prophylactic hemophilia treatment for individuals with inhibitors aged 12 years and older who, in some cases, currently have few options," said Anna Windle, SVP Clinical Development, Novo Nordisk. "As the first treatment of its kind for this population, Alhemo represents a significant step in helping to address the unmet needs of patients with hemophilia with inhibitors, highlighting Novo Nordisk's commitment to patient-centric innovations in rare diseases."
The primary objective from the pivotal Phase 3 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.
"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.
