FDA approves Alhemo for hemophilia A or B with inhibitors
1st subcutaneous injection of its kind for this patient population: Novo Nordisk
The U.S. Food and Drug Administration (FDA) has approved Novo Nordisk’s concizumab, which will be sold under the brand name Alhemo, as a daily treatment to prevent or reduce the frequency of bleeding episodes in certain adults and adolescents with hemophilia.
Eligible patients are those with hemophilia A or B, who are 12 and older, and have inhibitors, a type of neutralizing antibody against blood clotting proteins that can render standard preventive (prophylactic) treatments less effective.
“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,” Anna Windle, PhD, senior vice president of clinical development at Novo Nordisk, said in a company press release.
Alhemo has also been granted marketing authorization in Canada, Australia, Switzerland, Japan, and the European Union, although the specific patient groups eligible for treatment vary by country.
In contrast to many other prophylactic treatments that are given via infusions into the bloodstream (intravenous), Alhemo is given via under-the-skin (subcutaneous) injections, the first subcutaneous treatment of its kind to be approved for this patient population, Novo Nordisk noted.
Alhemo comes in prefilled, premixed injection pens at various concentrations
Alhemo can be administered by patients or caregivers after appropriate training. The treatment comes in prefilled, premixed injection pens at various concentrations and should be injected into the thigh or abdomen once daily.
“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,” Windle said.
People with hemophilia lack functional blood clotting proteins, making them susceptible to prolonged, excessive, and spontaneous bleeding episodes. In hemophilia A, the deficient blood clotting protein is factor VIII (FVIII), and in hemophilia B, it’s factor IX (FIX).
Factor replacement therapies are standard prophylactic treatments that provide patients with a version of the clotting protein they lack via regular intravenous infusions.
However, around 30% of people with severe hemophilia A and 5%-10% of those with severe hemophilia B develop inhibitors against FVIII or FIX, which can render factor replacement therapies less effective. Such patients may require nonfactor treatment options to prevent bleeds.
Inhibitors ‘most serious treatment-related complication’ in hemophilia
“The development of inhibitors remains the most serious treatment-related complication for people living with hemophilia,” said Amy Shapiro, MD, CEO and co-medical director at the Indiana Hemophilia & Thrombosis Center. “For patients with inhibitors, especially in hemophilia B, their hemophilia may remain poorly controlled and pose a life-threatening risk.”
Alhemo works by blocking a protein called tissue factor pathway inhibitor, which normally inhibits blood clotting by interfering with the production of a blood clotting enzyme called thrombin. In doing so, the treatment is expected to increase thrombin production and enhance blood clotting, thereby preventing bleeds in hemophilia patients regardless of the presence of inhibitors.
Novo Nordisk first applied to the FDA for Alhemo’s approval in 2023, but at the time, the regulatory body requested more information about the dosing and manufacturing of the treatment.
The FDA’s recent approval is based on data from the Phase 3 explorer7 trial (NCT04083781), where the treatment was found to reduce the rate of bleeds requiring treatment by 86% among hemophilia A and B patients with inhibitors relative to a group that received no prophylaxis treatment.
The median number of treated spontaneous and traumatic bleeds per year was zero for those given Alhemo, compared with 9.8 among those who were not on prophylaxis. Around two-thirds of patients (64%) on Alhemo experienced no spontaneous or traumatic bleeds that required treatment during the first six months, which was achieved by 11% of patients who were not on prophylaxis.
The most common side effects of Alhemo include injection site reactions and hives (urticaria). It shouldn’t be used by people with a history of serious allergic reactions to Alhemo or any of its ingredients.
“The approval of Alhemo … 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,” Shapiro said.
Another Phase 3 trial called explorer8 (NCT04082429) is testing Alhemo in patients with hemophilia A or B without inhibitors. Data from that study have indicated the preventive therapy similarly reduced bleeding episodes in that patient group relative to the group not on prophylaxis.
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