FDA issues CRL for Biomarin hemophilia gene therapy

In August 2020, the FDA issued a complete response letter (CRL) to Biomarin for Roctavian. The CRL asked for two years of follow-up data on the Phase 3 trial participants. Since this information will not be available until November 2021, the next FDA review date will most likely not occur until 2022.

Drug name: Roctavian (valoctocogene roxaparvovec)
Manufacturer: BioMarin
Condition: Severe hemophilia A

Condition overview

Hemophilia is a genetic bleeding disorder that prevents the blood from clotting normally. People with hemophilia may have spontaneous bleeding and/or they may start bleeding following injuries or surgery. There are different types of hemophilia, the most common are hemophilia A and B. The number of people with hemophilia A in the United States is estimated to be about 13,600 individuals.1 The severity of the disease is determined by the amount of Factor VIII (FVIII) protein found in the patient’s blood, which can be measured in a lab.

Current treatment

Most often, the patient’s factor protein is replaced through infusions of clotting factor concentrates. Given regularly, these infusions can help prevent severe bleeding from happening.

Today, the factor product category includes more than two dozen agents, with more in the pipeline. Over time, about 15 to 30 percent of people with hemophilia develop an antibody (inhibitor) that stops clotting factors from working properly. That makes it harder to treat excessive bleeding. These people need special treatment for their hemophilia until their bodies stop making the inhibitors. Physicians might prescribe high-dose clotting-factor concentrates, bypassing agents or immune-tolerance induction therapy.

Another commonly used therapy for hemophilia is Hemlibra® (emicizumab-kxwh), a bispecific factor IXa- and factor X-directed antibody indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A with or without factor VIII inhibitors.

Total cost of care per member may be $350,000 to $700,000 per year, and sometimes even more.

Roctavian overview

Roctavian is a one-time IV-administered gene therapy targeted for adults with severe hemophilia A, who have no history of factor VIII inhibitor, no active infections/immunosuppression and no comorbidities. According to BioMarin, this narrows the list of potential patients down to approximately 1,700.1

BioMarin’s CEO has been quoted in the media as saying he expects the treatment to be priced between $2 and $3 million.2 Based on the 50 percent drop in mean FVIII levels during year three compared to year one, long-term durability for the new therapy is currently unknown.3,4

Several other hemophilia gene therapies are in the pipeline.

A Citi Research survey of 60 U.S. hematologists showed they expect to switch 29 percent of Hemlibra® patients, and 34 percent of recombinant factor replacement patients over to gene therapy within a year after Roctavian becomes available. In three years, the numbers could expand to 38 percent from Hemlibra and 45 percent from factor product.5

PDUFA date: Late 2022
Benefit: Medical benefit

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References

1. American Thrombosis and Hemostasis Network letter to the Institute for Clinical and Economic Review on February 12, 2020. Accessed on July 22, 2010: https://icer-review.org/wp-content/uploads/2019/12/ICER_Hemophilia-A_Draft-Scope_Public-Comments_022520.pdf

2. JPM: Watch out, Roche. BioMarin’s gene therapy might bleed off the hemophilia A market. Accessed in January 2020 at: https://www.fiercepharma.com/marketing/watch-out-roche-biomarin-s-gene-therapy-might-bleed-out-hemophilia-a-market

3. Biomarin.com Morgan Stanley 17th annual global healthcare conference. Accessed in January 2020 at: https://investors.biomarin.com/events-presentations?item=63

4. Pasi KJ, Rangarajan MB, Mitchell N, et al. Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A. NEJM 2020; 382: 29-40.

5. JPM: Watch out, Roche. BioMarin’s gene therapy might bleed off the hemophilia A market. Accessed in January 2020 at: https://www.fiercepharma.com/marketing/watch-out-roche-biomarin-s-gene-therapy-might-bleed-out-hemophilia-a-market

Drug names are the property of their respective owners.