Valoctocogene Roxaparvovec MAA Granted Request for Accelerated Assessment

SAN RAFAEL, Calif., June 28, 2021 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) announced today that the company resubmitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for its investigational gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A. In May 2021, the EMA granted the Company's request for accelerated assessment.  Accelerated assessment potentially reduces the time frame for the EMA Committee for Medicinal Products for Human Use (CHMP) and Committee for Advanced Therapies (CAT) to review a MAA for an Advanced Therapy Medicinal Product (ATMP). A CHMP opinion is anticipated in the first half of 2022.  

The submission includes safety and efficacy data from the 134 subjects enrolled in the Phase 3 GENEr8-1 study, all of whom have been followed for at least one year after treatment with valoctocogene roxaparvovec, as well as four and three 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. 

"This is an important step to deliver the potential first gene therapy for people with hemophilia A.  The data package for this submission includes the largest Phase 3 study in any gene therapy for hemophilia A supported by up to four years of observation in a Phase 1/2 study," said Hank Fuchs, M.D., President, Worldwide Research and Development at BioMarin. "We look forward to the EMA reviewing the robust data set. We believe that valoctocogene roxaparvovec represents a scientific innovation that may become an important treatment choice for those people who have unmet medical needs."

"This submission is important for the bleeding disorders community given the need for continued scientific and medical innovation to provide a treatment option to address unmet needs for many people with hemophilia A," said Brian O Mahony FACSLM, Chief Executive, Irish Haemophilia Society. "We believe that therapeutic choices are critical for our community to provide access to alternative treatment approaches with the potential to address individual patient needs."

Applications are eligible for accelerated assessment if the CHMP and CAT decide the product is of major interest for public health, particularly from the point of view of therapeutic innovation. Evaluating a MAA under the EMA centralized procedure can take up to 210 days, not counting clock stops when applicants are requested to provide additional information. On request, the CHMP and CAT can reduce the time frame to 150 days if the applicant provides sufficient justification for an accelerated assessment, although an application initially designated for accelerated assessment can revert to the standard procedure during the review for a variety of reasons. The decision to grant accelerated assessment has no impact on the eventual CHMP and CAT opinion on whether a marketing authorization should be granted.

Regulatory Status

In the United States, BioMarin intends to submit two-year follow-up safety and efficacy data on all study participants from the Phase 3 GENEr8-1 study to support the benefit/risk assessment of valoctocogene roxaparvovec, as previously requested by the Food and Drug Administration (FDA). BioMarin is targeting a Biologics License Application (BLA) resubmission in the second quarter of 2022, assuming favorable study results, followed by an expected six-month review by the FDA.

The FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to valoctocogene roxaparvovec in March 2021. RMAT is an expedited program intended to facilitate development and review of regenerative medicine therapies, such as valoctocogene roxaparvovec, that are expected to address an unmet medical need in patients with serious conditions. The RMAT designation is complementary to Breakthrough Therapy Designation, which the Company received in 2017. 

In addition to the RMAT Designation and Breakthrough Therapy Designation, BioMarin's valoctocogene roxaparvovec also has received orphan drug designation from the FDA and EMA for the treatment of severe hemophilia A. The Orphan Drug Designation program is intended to advance the evaluation and development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. 

Robust Clinical Program

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 actively enrolling participants in 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. The Company is also 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, 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. 

About Hemophilia A

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. Additionally, people with the most severe form of hemophilia A (FVIII levels