FDA delayed approval of gene therapy drug

August 19, 2020

Why is Roctavian in the news?
It was expected to be the most expensive drug ever approved by the Food and Drug Administration (FDA), at an estimated price tag of as much as $3 million. However, Roctavian, the gene therapy for hemophilia A, failed to meet the FDA standards for approval on August 19, 2020.

Roctavian (valoctocogene roxaparvovec), developed by BioMarin Pharmaceuticals, is a one-time infusion that is expected to offer the ability of some patients with severe hemophilia A to go years without a need for treatment. Currently, hemophilia A patients are injecting treatments every couple of days.

Why was the anticipated FDA approval delayed?
It appears the FDA was concerned about the durability of the drug. A complete response letter (CRL) was issued by the FDA to BioMarin. In the letter, the FDA stated BioMarin must finish off the Phase 3 trial and submit two-year follow-up safety and efficacy data on all study participants. The last patient enrolled will not complete the two-year follow-up until November 2021, making mid-to-late 2022 the earliest the manufacturer could bring the drug to market.

Gene therapies are intended to fix the genetic defects that cause the disease(s) they treat through the use of new genetic material. Consequently, researchers look for diseases where gene therapies can offer a cure or make a significant medical difference. Genetic mutations in patients with hemophilia A inhibit the body’s ability to produce a protein needed to form blood clots. Roctavian contains a healthy copy of the affected gene, combined with other substances, to ensure the healthy gene is delivered to the right cells in order to restore the normal blood-clotting pathway in hemophilia A patients. Results showed substantial reduction in bleeding events and complete discontinuation and need for use of Factor VIII for prophylactic therapy, which could benefit many patients.

Gene therapies are typically once-per-lifetime drugs, and it is unlikely that Roctavian would be administered twice. A key unknown is if the beneficial effects wane over time, would patients have to return to previous therapies or wait for other hemophilia gene therapies to come to the market? This is one of the questions that may have led to the lack of approval.

What does this mean for payers and plan sponsors?
There are 20,000 patients with hemophilia in the U.S. BioMarin had expected drug approval would have offered therapy to an estimated 2,400 patients with hemophilia A in the U.S. Payers and plan sponsors will not have the worry of how to incur the extremely high cost of this gene therapy for now. Pharmaceutical Strategies Group will continue to monitor the status of Roctavian going forward.


1. https://www.cbsnews.com/news/fda-rejects-roctavian-anti-hemophilia-gene-therapy-biomarin-pharmaceutical/
2. https://hemophilianewstoday.com/2020/08/19/fda-delays-decision-roctavian-hemophilia-a-gene-therapy/
3. https://www.fiercebiotech.com/biotech/fda-gets-out-its-red-pen-again-rejecting-biomarin-s-gene-therapy-valrox-amid-durability
4. https://www.nytimes.com/2018/08/13/health/hemophilia-gene-therapy.html