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Val-Rox Approval Favored in Europe, Stalled in US

BioMarin received a positive CHMP opinion after the FDA delayed val-rox's BLA filing for the second time.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) has given a positive opinion to BioMarin’s valoctocogene roxaparvovec (val-rox; Roctavian) gene therapy for the potential treatment of hemophilia A.1

"Today's positive CHMP opinion for Roctavian addresses the unmet medical needs in severe hemophilia A by providing a treatment option that has been shown in clinical studies can maintain effective levels of endogenously produced coagulation Factor VIII over multiple years with a single intravenous administration. Currently available treatment options require long-term, chronic use with a high degree of compliance to a prescribed schedule to be effective," Hank Fuchs, MD, president, worldwide research and development, BioMarin, said in a statement.1

A final decision on val-rox's approval is expected from the European Commission in the third quarter of 2022. Meanwhile, in the US, the filing of BioMarin’s biologic license application was delayed again in June 2022 with the FDA requesting additional durability and safety data on the gene therapy.2 The BLA was previously rejected in August 2020 with requests for 2-year follow-up data.

BioMarin is working to collect the new data from ongoing trials, including GENEr8-1 (NCT03370913), GENEr8-3 (NCT04323098), and the non-clinical study GENEr8, and plans to resubmit the BLA by the end of September 2022 instead of June.

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"The positive CHMP opinion offers hope for a new treatment option for people with severe hemophilia A, who have been bound to lifelong treatment and still experience serious health complications, such as breakthrough bleeding, pain, and joint damage, as well as having to constantly consider their condition in all aspects of their lives," Johannes Oldenburg, MD, PhD, director, Institute of Experimental Haematology and Transfusion Medicine and Haemophilia Centre, University Clinic, Bonn, Germany, added to the statement.1 "The robust data set from the clinical trial program underscores the potential impact of gene therapy for patients, including a substantial and sustained reduction in bleeding that would have previously required Factor VIII infusions."

In March 2022, BioMarin announced the publication of results from the GENEr8-1 study in the New England Journal of Medicine that demonstrated val-rox's ability to restore endogenous factor VIII production and significantly reduce bleeding and use of enzyme replacement therapy in patients with hemophilia A.3

Investigators found that 132 human immunodeficiency virus–negative participants in GENEr8-1 had mean chromogenic substrate factor VIII activity levels during weeks 49 through 52 were 42.9 IU per deciliter (standard deviation [SD], 45.5) and median chromogenic substrate factor VIII activity levels were 23.9 IU per deciliter (interquartile range [IQR], 11.9-62.3). The mean change in factor VIII activity from baseline was 41.9 IU per deciliter (95% CI, 34.1-49.7; P <.001) and median change was 22.9 IU per deciliter (IQR, 10.9-61.3). Val-rox's safety profile was manageable, with all participants experiencing at least 1 mild adverse event (AE) and 5 participants experiencing treatment-related serious AEs.

REFERENCES
1. BioMarin receives positive CHMP opinion in Europe for valoctocogene roxaparvovec gene therapy to treat adults with severe hemophilia A. News release. BioMarin. June 24, 2022. https://investors.biomarin.com/2022-06-24-BioMarin-Receives-Positive-CHMP-Opinion-in-Europe-for-Valoctocogene-Roxaparvovec-Gene-Therapy-to-Treat-Adults-with-Severe-Hemophilia-A
2. BioMarin delays hemophilia a therapy valoctocogene roxaparvovec filing as FDA calls for more data. News release. BioMarin. May 31, 2022. https://www.biospace.com/article/fda-needs-more-data-for-biomarin-s-hemophilia-a-therapy/
3. Ozelo MC, Mahlangu J, Pasi J, et al. Valoctocogene roxaparvovec gene therapy for hemophilia A. New Eng J Med. 2022; 386: 1013-1025. doi: 10.1056/NEJMoa2113708