More Hemophilia Treatment Choices Despite Gene Therapy Setbacks

Hemophilia, a rare X-linked, inherited bleeding disorder, affects over 1.1 million people worldwide. Approximately 90% of those people are male, and an estimated 33,000 live in the United States. The disease is classified into different subtypes. Hemophilia A and hemophilia B are the two most common. With hemophilia A, there is a missing or defective blood clotting factor VIII; with hemophilia B, it’s factor IX. Of the two, hemophilia A is more prevalent.

Currently approved treatments for hemophilia A include rebalancing agents, factor replacement therapy, a factor VIII mimetic antibody and gene therapy. The sky-high hopes for gene therapy have been brought down to earth by how they have fared in the market, where the combination of multimillion-dollar price tags and lingering uncertainties about effectiveness and durability have worked against them. Even so, another gene therapy may join the hemophilia armamentarium, and another factor VIII mimetic is in the offing.

Mim8 (denecimig)

Furthest along the pipeline is Mim8 (denecimig), an investigational factor VIII mimetic bispecific antibody being developed by Danish company Novo Nordisk. Mim8 is designed to bridge factors IXa and X, thereby replacing the action of factor VIII.

The phase 3 FRONTIER 5 trial demonstrated that directly switching to Mim8 from Hemlibra (emicizumab), a bispecific factor IXa- and factor IX-directed antibody, without a washout period was safe and effective.

The researchers conducting the open-label study enrolled 61 patients ages 12 years and older with hemophilia A who received Hemlibra prophylaxis treatment. The participants had the option to receive Mim8 once a month, once every two weeks, or once a week, with the first dose administered on the next planned Hemlibra dosing day. The participants achieved a steady-state Mim8 concentration by week 16. By week 26, they were completely weaned off Hemlibra. The results showed a sustained increase in thrombin levels without excessive thrombin response that could lead to thromboembolic events. Additionally, a large majority of participants preferred the Mim8 pen injection system over their previous
Hemlibra injections.

If approved, Mim8 would offer flexible dosing options and a seamless transition from the current standard treatment for patients with hemophilia A. The company plans to submit its application for approval in the U.S. and the EU later in 2025.

BBM-H803

Even after Pfizer abandoned Beqvez (fidanacogene elaparvovec), its genetherapy for hemophilia B, and BioMarin scaled back marketing and production efforts for Roctavian (valoctocogene roxaparvovec), a gene therapy approved for hemophilia A, Chinese biotech company Belief BioMed is moving forward in developing BBM-H803, an investigational gene therapy for hemophilia A.

BBM-H803 is designed to deliver a working copy of the F8 gene to liver cells that would then produce factor VIII. The candidate is in a phase 1/2 trial evaluating its efficacy, safety and tolerability in adults with severe hemophilia A. Primary outcomes include the incidence of dose-limiting toxicity events, serious side effects, and treatment-related adverse events over six weeks.

The study has an estimated primary completion date of June 30, 2026, and Belief BioMed plans to initiate simultaneous phase 3 trials later this year.