FDA Greenlights Gene Therapy Roctavian for Severe Hemophilia A

The Food and Drug Administration (FDA) has approved Roctavian™ (valoctocogene roxaparvovec-rvox) for the treatment of adults with severe hemophilia A (congenital factor VIII [FVIII] deficiency with FVIII activity < 1 IU/dL) without preexisting antibodies to adeno-associated virus serotype 5 (AAV5) detected by an FDA-approved test.

Administered as a single-dose infusion, Roctavian is the first gene therapy approved for severe hemophilia A. The approval was based on data from the phase 3 GENEr8-1 study (ClinicalTrials.gov Identifier: NCT03370913), which evaluated the efficacy and safety of Roctavian in 134 adult males with severe hemophilia A. All patients received a single administration of Roctavian via intravenous infusion and were followed for 3 years.

Of the 134 patients who received the gene therapy, 112 had baseline annualized bleeding rate (ABR) data collected prospectively during a period of at least 6 months on FVIII prophylaxis. These patients experienced a mean ABR reduction of 52% after receiving Roctavian compared with their baseline ABR while receiving routine FVIII prophylaxis (2.6 bleeds/year vs 5.4 bleeds/year, respectively; mean difference in ABR, -2.8 [95% CI, -4.3, -1.2 bleeds/year]). Findings showed that the study met the pre-specified non-inferiority margin (3.5 bleeds/year), indicating the effectiveness of Roctavian.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” said Dr Steven Pipe, professor of pediatrics and pathology at the University of Michigan and an investigator in the phase 3 study.  “The approval of Roctavian, as the first gene therapy for severe hemophilia A, has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

According to BioMarin, patients treated with Roctavian in the clinical trial will be followed for up to 15 years in an extension study. Those who receive treatment after approval will be followed in real-world studies for 15 years or more.

The most common adverse reactions reported with Roctavian were nausea, fatigue, headache, infusion-related reactions, vomiting, and abdominal pain. Labs reported to be above the upper limit of normal included alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine phosphokinase, FVIII activity levels, gamma-glutamyl transferase, and bilirubin.

Roctavian is supplied in a single-dose vial containing a preservative-free suspension for intravenous infusion (nominal concentration of 2 × 10¹³ vg valoctocogene roxaparvovec-rvox per mL); each vial contains an extractable volume of not less than 8mL.

When selecting patients for treatment with Roctavian, baseline testing, including testing for pre-existing antibodies to AAV5, FVIII inhibitor presence, and liver health assessments should be performed. Patients with a positive test for antibodies to AAV5 or FVIII inhibitor, or those with active acute or uncontrolled chronic infections, known significant hepatic fibrosis or cirrhosis, or mannitol hypersensitivity should not receive Roctavian.

The FDA has also approved a companion diagnostic, AAV5 DetectCDx^™, to aid in the selection of adult patients eligible for treatment with Roctavian.