- BioMarin Pharmaceutical on Thursday expressed confidence in the approval chances of its hemophilia gene therapy Roctavian and a drug for a form of dwarfism recently submitted to the Food and Drug Administration, defending its plans to meet expectations for clinical trial data set by the agency.
- The path through regulatory review for both drugs — each crucial to BioMarin's future — is newly in question, following the FDA's unexpected rejection of Roctavian in August and recent reiteration to BioMarin of an advisory panel recommendation that could have bearing on the company's dwarfism drug.
- Wall Street analysts, asking questions of BioMarin leadership on a conference call Thursday, pressed the executives on their communications and relationship with the FDA. BioMarin R&D chief Henry Fuchs described the regulator as becoming more conservative.
Roctavian, which would have been the first gene therapy approved for hemophilia, was widely expected to secure the FDA's backing in August.
The surprise rejection, which hinged on differing results BioMarin obtained from an early and later-stage study of Roctavian, could set back the biotech's plans for a year or more. According to the company, the FDA wants to see at least two years of follow-up from the Phase 3 trial of Roctavian, much longer than what BioMarin had originally expected.
If that holds, BioMarin CEO Jean-Jacques Bienaimé said Thursday the company would be looking at a late 2022 launch for Roctavian. However, the study will return one-year results for all 134 participants by early next year, at which point some patients in the study would have longer follow-up, potentially out to 18 or 24 months.
Bienaimé indicated the company would then assess next steps for the program.
Trials have shown Roctavian, which delivers a functional gene that's mutated in patients with hemophilia A, can increase clotting protein levels in the blood, largely eliminating bleeding events and significantly reducing the need for regular treatment.
BioMarin had sought an accelerated approval for the therapy, relying on full results from a small study of about a dozen patients, coupled with an interim look at the first six months of the larger Phase 3 trial. The FDA ended up disagreeing, apparently concerned that patients in the Phase 3 study weren't faring as well as those in the earlier trial.
On the call Thursday, BioMarin executives expressed disappointment at the FDA's decision and fielded questions from analysts on why the company and agency ended up so far apart.
Fuchs, the R&D head, described the opposing views as a "different interpretation of the same set of facts," and hypothesized the agency had grown more conservative in its review of gene therapies.
"What we see across the board is that the agency has gotten very conservative in the last several months," said Fuchs. "They've had progressive leadership in the past. Oftentimes when the progressive leadership disappears, they retreat to conservative. And when stressed, they become conservative."
The FDA has approved two gene therapies for inherited diseases: Roche's Luxturna for a type of hereditary blindness and Novartis' Zolgensma for spinal muscular atrophy, a rare neuromuscular disorder.
Hemophilia, in contrast to those two diseases, is more common and has many available treatments that can keep the worst symptoms in check.
BioMarin is also awaiting the FDA's verdict on another drug, called vosorotide, for a form of dwarfism known as achondroplasia. The agency accepted the company's application for review earlier this month, but flagged recommendations from a 2018 advisory panel on achondroplasia treatment, which indicated a preference for two years of data from clinical trials.
BioMarin only has one year's worth of results from its Phase 3 trial, although it's accumulated much more data from a Phase 2 study. Still, company executives were confident the FDA would be convinced.
"We wouldn't have filed if we didn't think there was a substantial chance to get approved by the PDUFA date," said Fuchs.
For analysts on Wall Street, however, the feedback from the FDA appeared to introduce more uncertainty for a drug that's important to BioMarin's growth.
"2020 was meant to be a transformative year," wrote Joseph Schwartz, an analyst at SVB Leerink, in a Nov. 6 note to clients. "Instead, [BioMarin] is facing multiple challenges," with sales headwinds related to COVID-19 for its existing drugs adding to the regulatory uncertainty around Roctavian and vosorotide.