EMA Also Pushes Back Decision on Roctavian as Hemophilia A Gene Therapy

The European Medicines Agency (EMA) is asking for a full year’s worth of data from a Phase 3 trial of Roctavian as it considers approving this potential gene therapy for adults with severe hemophilia A, its developer, BioMarin, reported.

The request by the regulatory agency for the European Union pushes to at least 2021 its decision regarding Roctavian, whose marketing authorization application had been accepted and placed under accelerated review.

A similar request from the U.S. Food and Drug Administration, for complete, two-year follow-up results on the 134 patients in the GENEr8-1 trial (NCT03370913), was given to BioMarin on Aug. 18, just days before the FDA was expected to announce its decision.

“At the end of the day, health authorities want a larger data set given the highly innovative nature of gene therapy in hemophilia A,” Jean-Jacques Bienaimé, BioMarin’s chairman and CEO, said in a recent Baird web presentation.

“We are in a very fortunate position to be two months from completion of our global, one-year Phase 3 study,” Bienaimé added. “We now plan to share top-line, one-year Phase 3 data from this study in early 2021.”

BioMarin’s applications for Roctavian were supported by 26-week interim data on 16 patients in the GENEr8-1 trial and  three-year data from the Phase 1/2 trial (NCT02576795), called Study 270–201, in 15 patients.

The company decided to file approval requests based on preliminary Phase 3 results, Bienaimé said, after both the EMA and FDA gave Roctavian “accelerated” status — called a PRIME designation in Europe, and breakthrough therapy in the U.S.

BioMarin will work closely with the EMA on its updated filing, and Bienaimé noted that European officials already inspected and certified its manufacturing facility for Roctavian.

While one-year Phase 3 data is expected to be available around March, making an EMA decision possible next year, BioMarin does not anticipate finishing a two-year analysis until November 2021.

However, in upcoming discussions with the U.S. agency, it hopes to “harmonize” the data set “recommended” by the FDA and that sought by the EMA, said Hank Fuchs, president of worldwide research and development at BioMarin.

Roctavian’s possible approval by the EMA ahead of the FDA “might cause the U.S. regulators to think,” Fuchs added.

Roctavian is a gene therapy aimed at reducing, if not eliminating, the need for repeated factor VIII infusions by restoring production of the missing blood clotting protein in people with hemophilia A. It uses a harmless version of an adeno-associated virus (AAV), called AAV5, to deliver a shorter but functional copy of F8 — the gene that provides instructions to make factor VIII (FVIII) — to liver cells.

“While we’re a little disappointed with this delay, we believe that the package at launch will be even stronger with the full data results,” Bienaimé said. “And it will better position us commercially in Europe and allow us to obtain potentially better pricing and reimbursement … than if we were approved based on only 16 patients-worth of data six months after treatment.”

The company, he said, has confidence in both Roctavian’s effectiveness and its “approvability.”

Added Fuchs, noting that post-treatment changes in annualized bleeding rates is a trial goal, and “when we have that outcome, we’re no longer talking about ‘reasonably likely to predict a clinical benefit,’ we’re talking about demonstrated clinical benefit.”