Investigational Hemophilia Gene Therapy Achieves Clinical Criteria for FDA Review


Valoctocogene roxaparvovec (BioMarin) met pre-specified criteria for Factor VIII activity levels treating severe hemophilia A in a phase 3 clinical trial.

BioMarin Pharmaceuticals’ investigational gene therapy valoctocogene roxaparvovec for adults with severe hemophilia A met pre-specified clinical criteria for regulatory review, bringing it a step closer to FDA submission, according to a press release.

To meet pre-specified criteria for Factor VIII activity levels, 8 patients in the 20-patient cohort of the phase 3 GENEr8-1 study achieved Factor VIII levels of 40 international units per deciliter (IU/dL), or more, at 23 to 26 weeks.

The phase 3 program for valoctocogene roxaparvovec includes 2 studies: GENEr8-1 and GENEr8-2. In GENEr8-1, 130 total participants are included to evaluate superiority of the gene therapy with the 6e13 vg/kg dose compared with the standard of care, prophylactic therapy. Enrollment completion in the newly amended GENEr8-1 study is expected in the third quarter of 2019, according to the release.

GENEr8-2, which includes the 4e13 vg/kg dose, remains unchanged with an N=40 and is expected to complete enrollment after GENEr8-1 in 2019.

In the GENEr8-1 study, the estimated median annual bleed rate (ABR) for the 16 patients who had reached week 26 by the April 30 cutoff since administration of valoctocogene roxaparvovec was 0 and the estimated mean ABR was 1.5, representing a reduction of 85% from baseline levels where all patients were on standard of care prophylaxis. Additionally, the study showed an 84% reduction in median annualized Factor VIII usage and a 94% reduction in mean FVIII usage annualized between weeks 5 and 26. In the 23 to 26 week time period, the mean Factor VIII level using the CS assay was 36 IU/dL and the median was 33 IU/dL.

Valoctocogene roxaparvovec was well-tolerated by 22 patients in the phase 3 cohort at the 6e13 vg/kg dose. No participants developed inhibitors to Factor VIII and no participants withdrew from the study.

“Reaching this pre-specified clinical endpoint is an important milestone that brings us 1 step closer to a potential regulatory submission in both the US and Europe for valoctocogene roxaparvovec to treat adults with severe hemophilia A,” Hank Fuchs, MD, president of the Worldwide Research and Development at BioMarin, said in a statement.

The company will now meet with the FDA and European Medicines Agency (EMA) to review the phase 3 data and other elements of a submission.

“Our discussions with the FDA and EMA underscore the high level of unmet need in the hemophilia community, and we look forward to continuing our productive dialogue on the submissions,” Dr Fuchs said.

Valoctocogene roxaparvovec has also received Breakthrough Therapy and Orphan Drug designations from the FDA for this indication, according to BioMarin. The company expects to announce the timing for its planned marketing applications in 3Q 2019.


BioMarin Announces that Phase 3 Cohort of Valoctocogene Roxaparvovec, Gene Therapy Study in Severe Hemophilia A Met Pre-Specified Criteria for Regulatory Submissions in the US and Europe [news release]. BioMarin. Accessed May 30, 2019.

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