BioMarin plans to resubmit the biologics license application for val-rox to the FDA by the end of September 2022.
Roctavian (valoctocogene roxaparvovec), BioMarin’s gene therapy for treating severe hemophilia A, has been approved in the EU with conditional marketing authorization.
The conditional authorization is for adult patients without a history of factor VIII (FVIII) inhibitors and without detectable antibodies to adeno-associated virus (AAV) serotype 5. The European Commission (EC) also decided to maintain Roctavian’s orphan drug designation and granted a 10-year period of market exclusivity.
"This approval in the EU represents a medical breakthrough in the treatment of patients with severe hemophilia A that expands the conversation between a patient and physician on treatment choices to now include a one-time infusion that protects from bleeds for several years," Johannes Oldenburg, MD, Director, Institute of Experimental Haematology and Transfusion Medicine and Haemophilia Centre, University Clinic, Bonn, Germany, said in a statement.1 "It is exciting to imagine the possibilities of this approved gene therapy, which has demonstrated a substantial and sustained reduction in bleeding for patients, who potentially could be freed from the burden of regular infusions."
The approval was based off positive data from the phase 3 GENEr8-1 study (NCT03370913 which were published in the New England Journal of Medicine. Investigators found that val-rox restored endogenous FVIII production and significantly reduced bleeding and use of enzyme replacement therapy in 132 human immunodeficiency virus–negative participants with hemophilia A.2
These patients had a mean chromogenic substrate FVIII activity level of 42.9 IU per deciliter (standard deviation [SD], 45.5) during weeks 49 through 52 and a median chromogenic substrate FVIII activity level of 23.9 IU per deciliter (interquartile range [IQR], 11.9-62.3). The mean change in FVIII 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 had a manageablesafety profile, with all participants experiencing at least 1 mild adverse event (AE) and 5 participants experiencing treatment-related serious AEs.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) previously gave a positive opinion to the therapy in June 2022 while the filing of BioMarin’s BLA was delayed again due to the FDA’s request for additional durability and safety data.3,4 The BLA was first rejected in August 2020 with requests for 2-year follow-up data. With the EC’s approval, BioMarin has reiterated their intent to resubmit the BLA by the end of September 2022 and believes that an extra 3 months of review in addition to the standard 6 months of review will be needed due to the large amount of data.
"Roctavian approval in Europe is a historic milestone in medicine and is built upon almost four decades of scientific discovery, innovation, and perseverance. We thank the European Commission for recognizing Roctavian's value as the first gene therapy for hemophilia A, a feat that we believe will transform how healthcare professionals and the patient community think about caring for bleeding disorders," Jean-Jacques Bienaimé, chairman and chief executive officer, BioMarin, added to the statement.1 "We are grateful to the patients, investigators and community, who dedicated their time and effort to this achievement and whose aspirations provided the driving force behind making this one-time therapy a reality."