EMA OKs Biomarin’s New Application to Approve Roctavian

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Roctavian in Europe


The European Medicines Agency (EMA) has validated BioMarin Pharmaceutical’s new application seeking approval of its investigational one-time gene therapy Roctavian (valoctocogene roxaparvovec) for severe hemophilia A.

The application was resubmitted to EMA following a request for longer follow-up data from the Phase 3 GENEr8-1 clinical trial (NCT03370913), which is investigating the efficacy of the gene therapy in 134 patients. The same had been requested by the U.S. Food and Drug Administration (FDA)  due to concerns regarding the therapy’s durability.

The application’s review, which was given accelerated assessment, will be conducted by the Committee for Medicinal Products for Human Use (CHMP) and the Committee for Advanced Therapies (CAT), two arms of the EMA.

A decision is expected by June 2022. If accepted, Roctavian will be the first gene therapy approved in Europe for hemophilia A.

“We look forward to working with the agency as it evaluates the robust data set in this application, which we believe address the requests made during the prior MAA [marketing authorization application] review,” Hank Fuchs, MD, said in a press release. Fuchs is president of worldwide research and development at BioMarin.

“We believe that this gene therapy has the potential to fulfill the unmet medical needs in the community,” Fuchs added.

Roctavian, administered as a single into-the-vein injection, uses a harmless adeno-associated virus to deliver a shorter, but functional, copy of F8 — the gene that provides instructions to make factor VIII (FVIII) — to cells in the liver. The liver is the major organ responsible for producing the body’s clotting factors. FVIII is the blood-clotting protein missing in hemophilia A patients.

This gene therapy aims to boost FVIII production and reduce, or possibly

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eliminate, the need for preventive FVIII replacement therapy, a standard treatment used to avoid spontaneous bleeds in these patients.

BioMarin’s resubmission includes safety and effectiveness data from at least one year of follow-up from the 134 patients enrolled in the GENEr8-1 trial.

It also includes three– and four-year follow-up data from patients given two doses of the therapy — 4e13 vector genomes per kilogram (vg/kg) and 6e13 vg/kg — in an ongoing Phase 1/2 dose escalation study (NCT02576795). 

Previously reported top-line, one-year data from GENEr8-1 showed the investigational gene therapy led to a significant increase in the levels of FVIII, meeting the trial’s main goal. The study also achieved key secondary goals, with Roctavian effectively lowering bleeding rates and the need for replacement therapy.

“This pivotal study demonstrated superiority of valoctocogene roxaparvovec compared to the standard of care, prophylactic Factor VIII replacement,” said Fuchs.

Similar reductions in bleeding rates and use of preventive replacement therapies also were observed in patients who received the experimental therapy in the dose escalation Phase 1/2 study.

“The extensive data set for valoctocogene roxaparvovec is supported by decades of scientific and clinical research in the field of gene therapy.  We continue to contribute to the body of scientific knowledge and will be sharing results from our Phase 1/2 and Phase 3 studies with the community at the International Society on Thrombosis and Haemostasis (ISTH) 2021 Congress next week,” Fuchs said.

The ISTH Congress begins Saturday and runs through Wednesday, It is a global virtual event with interactive components being hosted from Philadelphia, Pennsylvania.