Weekly Dose of Hemophilia Factor VIII Therapy Delivers Significant Bleed Protection

Hemophilia, a genetic bleeding disorder caused by low levels of factor VIII or factor IX, is associated with a substantial burden to patients and the health care system, prompting the need for new treatment options.¹

The number of people living with hemophilia in the United States is estimated between 22,000 and 33,000, according to data from federally funded hemophilia treatment centers. It affects primarily men with approximately 1 in 5000 males diagnosed at birth, about 400 annually.¹ 

The most common two types are hemophilia A, caused by a lack of clotting factor VIII, and the rarer hemophilia B, caused by a lack or decrease of clotting factor IX.¹ Hemophilia A is 4 times as common as B, and affects all races and ethnic groups.² 

Hemophilia A can additionally be categorized by severity based on the levels of defective factor III in their blood.

• Mild: 6% up to 49% of factor VIII
• Moderate: 1% up to 5% of factor VIII
• Severe: <1% of factor VIII

The annual cost of treatment of hemophilia A ranges from $59,101 for those with mild disease to $301,392 for patients with severe disease receiving prophylaxis, according to estimates in 2018. Factor replacement products represent up to 94% of total cost for severe disease.⁴ One study estimated that the overall cost per patient with hemophilia and complications associated with the development of inhibitors at $1 million annually. Indirect costs are also substantial and include individuals’ and caregivers’ lost productivity, caregivers’ unpaid costs, and individuals’ hemophilia-related disability.⁵

Treatment Landscape

“The main medication to treat hemophilia A is concentrated FVIII product, called clotting factor or simply factor,” states the National Hemophilia Foundation. “There are two types of clotting factor: plasma-derived and recombinant. Plasma-derived factor is made from human plasma. Recombinant factor products are developed in a lab through the use of DNA technology. While plasma-derived factor VIII products are still available, approximately 75% of the hemophilia community takes a recombinant FVIII product.”

One of the primary challenges associated with effectively treating and managing hemophilia is the rate of needed infusions or treatment to avoid severe bleeding episodes.

Latest Approval

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl, previously efanesoctocog alfa (Altuviiio, Sanofi), a first-in-class, high-sustained factor VIII replacement therapy was granted FDA approval for patients with hemophilia A in February 2023.^6-8 

Approval was based on results from the phase 3 XTEND-1 study in which once-weekly Altuviiio prophylaxis demonstrated significant bleeding protection among patients aged 12 years or older.⁷ 

Patients were divided into 2 groups with group A receiving once-weekly prophylaxis with Altuviiio (50 IU per kilogram of body weight) for 52 weeks and group B patients received on-demand treatment with Altuviiio for 26 weeks, followed by once-weekly prophylaxis with Altuviiio for 26 weeks.⁷

“Once-weekly Altuviiio prophylaxis met the primary endpoint, providing significant bleed protection for people with severe hemophilia A with a mean annualized bleeding rate (ABR) of 0.70 (95% CI: 0.5-1.0) and a median ABR of 0.0 (Q1, Q3: 0.0, 1.0),” stated Sanofi in a press release.⁸ “Altuviiio met the key secondary endpoint with a significant reduction of 77% in ABR versus prior factor prophylaxis based on an intra-patient comparison (95% CI:58%-87%).”

Additional trials are being conducted to better understand severe cases, pediatric outcomes, and the long-term safety and efficacy; however, this approval is a significant step forward in improving therapy options for patients.  

“This approval marks an important clinical advancement for the hemophilia community because we have an option that can achieve higher levels of factor activity with a single simplified weekly dose,” said Lynn Malec, MD, medical director, Comprehensive Center for Bleeding Disorders, associate investigator, The Versiti Blood Research Institute, and associate professor of medicine and pediatrics at The Medical College of Wisconsin, in a Sanofi Press release. “By maintaining high levels of factor activity throughout the week, patients can be confident in the bleed protection Altuviiio offers.”

References:

1. Centers for Disease Control and Prevention. Hemophilia. Reviewed February 28, 2023. Accessed March 6, 2023. https://www.cdc.gov/ncbddd/hemophilia/index.html 
2. National Hemophilia Foundation. Hemophilia A: an overview of symptoms, genetics, and treatments to help you understand hemophilia A.  Accessed March 25, 2023. https://www.hemophilia.org/bleeding-disorders-a-z/types/hemophilia-a
3. Rosenberg J. Hemophilia: treatment landscape, costs, and disease management. April 26, 2018. Accessed March 28, 2023. https://www.ajmc.com/conferences/amcp-2018/hemophilia-treatment-landscape-costs-and-disease-management-
4. Dalton DR. Hemophilia in the managed care setting. Am J Manag Care. 2015;21(6):S123-S130.
5. Asimopoulos M. FDA approves factor viii replacement therapy for hemophilia A. March 9, 2023. Accesed March 25, 2023. https://www.hmpgloballearningnetwork.com/site/frmc/news/fda-approves-factor-viii-replacement-therapy-hemophilia
6. NEJM publishes once-weekly efanesoctocog alfa Phase 3 data demonstrating its potential to transform the treatment landscape for people with hemophilia A. Press release. Sanofi. January 25, 2023. Accessed March 26, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-01-25-22-30-00-2595681
7. von Drygalski A, Chowdary P, Kulkarni R, et al. Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A. https://www.nejm.org/doi/full/10.1056/NEJMoa2209226
8. FDA approves once-weekly ALTUVIIIO™, a new class of factor VIII therapy for hemophilia A that offers significant bleed protection. Press release. Sanofi. February 23, 2023. Accessed March 26, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-02-23-21-00-00-2614759