FDA approves ALTUVIIIO label update (Dec 2025) adding factor VIII inhibitor risk from post-marketing data. Details on warnings, trials, and clinician advice for hemophilia A prophylaxis
Written By: Pharmacally Medical News Desk
Recently, the U.S. Food and Drug Administration (FDA) approved a labelling supplement for ALTUVIIIO (Efanesoctocog alfa), requiring updates to two key sections: Warnings and Precautions (Section 5) and Adverse Reactions (Section 6). The decision is based on post-marketing safety data, particularly reports of factor VIII inhibitor development.
ALTUVIIIO is a once-weekly recombinant factor VIII therapy approved in 2023 for prophylaxis, on-demand bleeding control, and perioperative management in hemophilia A. It was designed to maintain sustained factor VIII levels and reduce bleeding frequency while offering convenient dosing. Since approval, the product has remained under continuous safety surveillance through routine pharmacovigilance activities.
What Changed in the Label
Stronger language on inhibitor development (Section 5)
The revised label emphasizes that neutralizing antibodies (inhibitors) have been reported after approval. It advises:
- Regular monitoring for inhibitors
- Investigating unexpected bleeding or inadequate factor VIII levels
- Testing when treatment response appears reduced
This ensures clinicians remain alert to immunogenicity risks seen in wider real-world use.
Post-marketing reporting added to Section 6
The Adverse Reactions section now formally lists factor VIII inhibitor development as a post-marketing event. Including this in the label increases transparency and clinical awareness without changing indications or dosing guidance.
Sanofi/Bioverativ Response
Bioverativ (a Sanofi company) responded to the FDA letter by submitting revised labeling text, integrating the agency’s agreed language into both the Warnings and Adverse Reactions sections. The company also committed to updating the structured electronic labeling and ensuring that patient materials reflect the new information. In addition, Bioverativ confirmed that future advertising and promotional content will align with the updated safety wording. Overall, the exchange reflects a cooperative regulatory process focused on ongoing safety refinement, rather than a corrective or punitive action.
In clinical trials (XTEND-1, XTEND-Kids), no inhibitors were detected. However, as use expanded, spontaneous post-marketing safety reports described cases of inhibitor development, consistent with what is already known for all factor VIII replacements.
Clinically, inhibitor formation remains a well-recognized risk across factor VIII replacement therapies, including extended-half-life (EHL) products, even though the frequency is relatively low in previously treated patients. Inhibitors antibodies that neutralize infused factor VIII can make replacement therapy ineffective and are one of the most significant complications in hemophilia A management, occurring in up to about 30 percent of patients overall and a smaller percentage in those with prior exposure to factor VIII products.
Although many EHL products have improved bleeding outcomes by reducing infusion frequency and maintaining higher trough levels compared with standard-half-life therapies, studies have reported cases of inhibitor emergence with some EHL factor VIII products in clinical development and practice settings. Including inhibitor risk in ALTUVIIIO’s updated label aligns it with this broader body of experience indicating that immunogenic responses, while uncommon, can occur with factor VIII products in the real world, reinforcing the importance of monitoring and early detection.
Guidance for Clinicians and Patients
Clinicians should continue routine bleeding prophylaxis according to current recommendations and maintain vigilance for inhibitor development. Testing for inhibitors is advised when bleeding control worsens or when expected plasma factor VIII levels are not achieved. Any suspected safety events should be documented and reported through appropriate pharmacovigilance channels, as early recognition allows timely treatment adjustments and helps prevent prolonged bleeding complications.
Patients should be encouraged to report unusual bleeding, lack of response to treatment, or any worsening symptoms without delay. The FDA’s updated labeling for ALTUVIIIO reflects evolving real-world experience showing that inhibitor development can occur, although it remains uncommon. Including this information in the label strengthens awareness for both prescribers and patients. Sanofi/Bioverativ worked with the FDA to implement these revisions promptly.
Reference
Supplement Approval, US FDA, 29 December 2025, https://www.fda.gov/media/190431/download?attachment
ALTUVIIIO, updated highlights of prescribing information, https://www.fda.gov/media/165594/download
Lynn Malec et al, Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A, N Engl J Med 2024;391:235-246, DOI: 10.1056/NEJMoa2312611
ALTUVIIIO is the first FVIII replacement therapy to overcome the half-life limitations imposed by VWF, https://www.sanofimarketaccess.com/products/specialty-care/altuviiio/clinical-evidence
Kim JY, You CW. The prevalence and risk factors of inhibitor development of FVIII in previously treated patients with hemophilia A. Blood Res. 2019 Sep;54(3):204-209. doi: 10.5045/br.2019.54.3.204. Epub 2019 Sep 25. PMID: 31730688; PMCID: PMC6779946.
Tiede A, Half‐life extended factor VIII for the treatment of hemophilia A, Journal of Thrombosis and Haemostasis, Volume 13, Supplement 1, 2015, Pages S176-S179, https://doi.org/10.1111/jth.12929.
