BioMarin's hemophilia gene therapy may face further delays over fresh FDA requests

Despite getting the green light in Europe this summer, BioMarin’s hopes for bringing its hemophilia gene therapy to the U.S. remain as distant as ever, with the FDA now requesting a look at its manufacturing site and long-term phase 3 data.

Back in May, the company revealed that the FDA had asked additional questions about the one-and-done therapy, called valoctocogene roxaparvovec or Roctavian, pushing back an anticipated approval decision date to September. BioMarin resubmitted its application last month, prompting the agency to request an inspection of the company’s gene therapy manufacturing facility in Novato, California, as well as an upcoming three-year data analysis from the phase 3 GENEr8-1 trial.

While the company had been banking on an updated decision date of March 31, 2023, the FDA has said submitting the new information may count as a major amendment to the application. This would push back the decision date by a further three months, said BioMarin, although the company noted the FDA would evaluate the new data before making that call.

The FDA had previously communicated plans to hold an advisory committee meeting at some point. BioMarin said it looked “forward to the opportunity to discuss the recently requested 3-year data analysis with the advisory committee.”

"We appreciate the level of engagement from FDA this early in their BLA review cycle and are pleased to share that the inspection of our gene therapy manufacturing facility has now been scheduled,” Hank Fuchs, M.D., president of worldwide research and development at BioMarin, said in the release.

“Additionally, with their request related to the upcoming three-year data analysis from our phase 3 GENEr8-1 study, FDA stated that these data are expected to provide longer-term efficacy and safety information and would thus be useful to people with hemophilia A and healthcare providers in making better and more informed decisions when considering valoctocogene roxaparvovec as a treatment choice should it be approved."

Fuchs added that the company had been encouraged by the bleed control results, shared in January, from the first cohort of patients who had reached three years of observation in the phase 3 study. The company expects to share the full three-year results from all 134 participants in early 2023, he said.

The FDA’s request marks the latest hurdle in a strung-out regulatory process for ValRox after it was initially rejected in August 2020 over durability concerns. At the time, the agency recommended that BioMarin compile two years of safety and efficacy data from the phase 3 trial, data that became available in November 2021. In January 2022, BioMarin reported that bleeding events remained rare two years post-treatment among trial participants, teeing up a second go at approval. 

The U.S. holdups are especially noticeable for a drug that snagged a European approval back in August. However, BioMarin isn’t the only company that’s run into trouble getting its hemophilia drug to market. Pfizer and its partner Sangamo Therapeutics had an FDA hold slapped on their hemophilia A gene therapy for four months before it was lifted, although the company didn’t restart dosing until last month, while CSL Behring’s hemophilia B gene therapy similarly faced a hold and subsequent lift—with the med since securing an FDA priority review.