Gene therapy for hemophilia A patients in the U.S. will have to wait. The FDA needs more time to review data from BioMarin Pharmaceuticals, and the agency told the company it won’t be able to issue a regulatory decision by the end of March.
The new date for a decision is June 30, which comes nearly three years after the FDA initially rejected BioMarin’s application for its gene therapy, Roctavian. Since then, the company has accrued more data from patients followed for a longer period of time.
Hemophilia A is an inherited disorder in which patients lack sufficient amounts of a clotting protein called factor VIII. Standard of care includes regular infusions of factor VIII therapies. Roctavian, a functioning version of the gene that produces factor VIII, is intended to be a one-time treatment.
BioMarin has run what it says is the longest and largest clinical trial for a gene therapy for hemophilia. The Phase 3 study enrolled 134 patients with severe hemophilia A, all but two of whom continued in the study through year three. At the start of 2023, the biotech reported preliminary three-year results showing that the therapy reduced annualized bleeding rates by an average of 80% from baseline. The data also showed the therapy reduced the use of factor VIII therapy by 94% in year three compared to baseline.
The FDA accepted BioMarin’s resubmitted Roctavian application last October, setting a March 31 target date for a regulatory decision. In January, the biotech said it would share with the agency the latest cut of clinical data, acknowledging that these results could extend Roctavian’s review time. After Monday’s market close, BioMarin said the FDA determined that the three-year data analysis was a major amendment to the biologics license application, and the review timeline would be extended by three months.
Last August, the European Commission awarded Roctavian conditional marketing authorization based on two-year clinical data for the therapy. In a research note sent to investors Tuesday, William Blair analyst Tim Lugo wrote that the FDA delay was expected, due to the additional data submitted by the company. But he added that he expects an affirmative FDA decision for the gene therapy, followed by a product launch in the third quarter of this year.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
“We believe that the two-year data from the GENEr8-1 study were clearly positive, supporting the European approval of the product,” Lugo said. “Three-year data continue to support the profile of Roctavian and support approval of the product in the United States, in our view.”
Roctavian would compete against factor VIII therapies, including Sanofi’s new factor VIII fusion protein, Altuviiio, approved by the FDA late last month, as well as non-factor therapies such as Roche’s blockbuster bispecific antibody drug, Hemlibra. Meanwhile, a hemophilia A gene therapy from Roche subsidiary Spark Therapeutics is in Phase 3 testing. Hemgenix, a CSL Behring treatment for the rarer hemophilia B, last fall became the first approved gene therapy for either form of hemophilia.
Despite the competition in hemophilia A, Lugo sees plenty of opportunity for Roctavian. He said this gene therapy along with the recently launched Voxzogo, approved to treat dwarfism from achondroplasia, are the two largest potential products in BioMarin’s history, giving the biotech the opportunity to more than double its revenue in the next few years. BioMarin’s 2022 annual report shows product revenue of more than $2 billion, up 14.5% from the prior year.
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