The U.S. Food and Drug Administration (FDA) has approved BioMarin’s gene therapy [valoctocogene roxaparvovec-rvox (Roctavian)] to treat adults with severe hemophilia A.
This is an adeno-associated virus vector (AAV)–based gene therapy and will be a one-time infusion that delivers a functional gene designed to allow the patient to produce FVIII on their own, thereby reducing the need for ongoing prophylaxis.
Hemophilia A is a rare bleeding disorder that reduces a person’s ability to properly develop blood clots and is due to a lack of functioning FVIII. Hemophilia A occurs mostly in males. People with hemophilia can experience bleeding episodes that can cause pain, irreversible joint damage and life-threatening hemorrhages. Persons with severe hemophilia A account for approximately 50% of the hemophilia A population. These individuals are treated, at least until today, with a prophylactic regimen of intravenous factor VIII infusions administered 2-3 times per week or a bispecific monoclonal antibody (emicizumab) 1-4 times per month.
The gene therapy approval is largely based on the Phase 3 GENEr8-1 study. In that study, 112 patients with severe hemophilia A had a mean annualized bleeding rate (ABR) reduction of 52%. Reductions in spontaneous bleeds and joint bleeds were also reported. According to BioMarin, many of these patients have now been followed for over three years and they continue to do well. At the recent International Society on Thrombosis and Haemostasis (ISTH) meeting, study participants had an 82.9% reduction in treated bleeds and a 96.8% reduction in FVIII usage overall (compared to baseline levels).
The most common adverse reactions with the gene therapy were nausea, fatigue, headache, infusion-related reactions, vomiting, and abdominal pain.
The most common laboratory abnormalities were alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CPK), factor VIII activity levels, gamma-glutamyl transferase (GGT) and bilirubin > upper levels of normal (ULN). The majority of patients in the clinical trial required corticosteroids for ALT elevation (median duration of corticosteroid use was 35 weeks).
It is estimated that there are approximately 6,500 adults living with severe hemophilia A in the U.S. BioMarin expects approximately 2,500 of those adults to be eligible to receive the gene therapy.
According to several news organizations the Washington Post, the price for this one time infusion will be $2.9 million.
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