BioMarin Receives Positive European CHMP Opinion for Gene Therapy to Treat Adults with Severe Hemophilia A

The Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending conditional marketing authorization for BioMarin Pharmaceutical’s investigational gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A.

Photo: Hank Fuchs, president of Worldwide Research and Development at BioMarin

A final approval decision, typically consistent with the CHMP recommendation, is expected from the European Commission in the third quarter of 2022.

The one-time infusion is planned to be marketed under the brand name Roctavian for the treatment of severe hemophilia A (congenital factor VIII deficiency) in adult patients without a history of Factor VIII inhibitors and without detectable antibodies to adeno-associated virus serotype 5 (AAV5). Roctavian is the first gene therapy to be recommended for approval in Europe for hemophilia A.

“Today’s positive CHMP opinion for Roctavian addresses the unmet medical needs in severe hemophilia A by providing a treatment option that has been shown in clinical studies can maintain effective levels of endogenously produced coagulation Factor VIII over multiple years with a single intravenous administration,” said Hank Fuchs, president of Worldwide Research and Development at BioMarin. “Currently available treatment options require long-term, chronic use with a high degree of compliance to a prescribed schedule to be effective.”

Hemophilia A is an X-linked genetic disorder caused by missing or defective Factor VIII, a clotting protein. People living with hemophilia A lack sufficient functioning Factor VIII protein to help their blood clot and are at risk for painful and/or potentially life-threatening bleeds from even modest injuries. About half of the people with hemophilia A have the severe form of the disease and often experience painful, spontaneous bleeds into their muscles or joints.

The standard of care for patients with severe hemophilia A is chronic lifelong injectable therapy to maintain enough clotting factor in the bloodstream to prevent bleeds. BioMarin’s investigational valoctocogene roxaparvovec gene therapy works by delivering a functional gene that is designed to enable the body to produce FVIII on its own with the goal of reducing the need for ongoing prophylaxis.

It is estimated that more than 20,000 adults across Europe, Middle East, and Africa are affected by severe hemophilia A. BioMarin anticipates additional patient access through named patient sales based on an EMA approval in countries in the Middle East and Africa and expects additional market registrations to be facilitated by an anticipated EMA license.

The CHMP based its positive opinion on the totality of data from the valoctocogene roxaparvovec clinical development program, the most extensively studied gene therapy for hemophilia A, including two-year outcomes from the global GENEr8-1 Phase 3 study, supported by five and four years of follow-up from the 6e13 vg/kg and 4e13 vg/kg dose cohorts respectively, in the ongoing phase 1/2 dose escalation study. BioMarin has committed to continue working with the broader community to monitor the long-term effects of treatment. Overall, single 6e13 vg/kg dose of valoctocogene roxaparvovec has been well tolerated with no delayed-onset treatment related adverse events.

The conditional marketing authorization (CMA) recognizes that benefit to public health of the immediate availability on the market outweighs the uncertainties inherent to the fact that the science is still new, as is the case with any gene therapy, and the fact that additional data are still required. Once EMA has granted a CMA, BioMarin will provide further data from ongoing studies within defined timelines to confirm that the benefits continue to outweigh the risks, building on what already constitutes the largest clinical data package for gene therapy in hemophilia A. Conversion to a standard marketing authorization will be contingent on the provision of additional data from currently ongoing Roctavian clinical studies, including longer-term follow up of patients enrolled in the pivotal trial GENEr8-1, as well as a study of corticosteroids for which enrollment is now complete.  The final summary of product characteristics will be available when the product is approved by the European Commission.

The CHMP opinion differed from that of U.S. Food and Drug Administration, which issued a Complete Response Letter in August 2020 with the recommendation that the company submit two years of follow-up safety and efficacy data on all study participants.

BioMarin has multiple clinical studies underway in its comprehensive gene therapy program for the treatment of hemophilia A. In addition to the global phase 3 study GENEr8-1 and the ongoing phase 1/2 dose escalation study, the company is also conducting a phase 3B, single arm, open-label study to evaluate the efficacy and safety of valoctocogene roxaparvovec at a dose of 6e13 vg/kg with prophylactic corticosteroids in people with hemophilia A (Study 270-303). In addition, the company is running a phase 1/2 Study with the 6e13 vg/kg dose of valoctocogene roxaparvovec in people with hemophilia A with pre-existing AAV5 antibodies (Study 270-203), as well as another phase 1/2 Study with the 6e13 vg/kg dose of valoctocogene roxaparvovec in people with hemophilia A with active or prior FVIII inhibitors (Study 270-205).

Author: Rare Daily Staff