• BioMarin Pharmaceutical plans on submitting its hemophilia A gene therapy to U.S. and European regulators sometime in the fourth quarter, which could bring approval decisions as early as mid-2020.
• Supporting the submissions for valrox are an ongoing Phase 1/2 study as well as an interim analysis of a Phase 3 investigation. In a Monday presentation, three-year data from the earlier trial showed almost all patients who got a one-time dose of valrox continue to not need infusions of blood clotting protein. BioMarin said the results represent a 96% reduction in patients’ mean annualized bleed rates.
• Fourth quarter filings would affirm BioMarin’s leading position over rival companies developing hemophilia A gene therapies. The next closest is Spark Therapeutics, which has also advanced its SPK-8011 into late-stage testing. Sangamo and Pfizer are further behind, but just last week announced positive data for the high dose of their treatment, SB-525.

Hemophilia has become one of the most competitive battlegrounds in the emerging field of gene therapy. While BioMarin remains the frontrunner to market, a key question moving forward is whether valrox (valoctocogene roxaparvovec) primes the well for additional therapies — or dries it up.

BioMarin intends to first get an accelerated approval of valrox, and then later secure a full approval based on results from the ongoing Phase 3 study. Henry Fuchs, head of the company’s R&D, said in June he hoped the full approval would “become a barrier to entry” for others trying to go down the accelerated path, as it could require them “to do a larger and longer study to get on the market.”

Yet an approval of any sort may create competitive challenges.

SVB Leerink analyst Mani Foroohar argued in an interview with BioPharma Dive earlier this year that enrolling clinical trials for rare disease gene therapies will become more difficult once patients have an approved option.

That doesn’t seem to be deterring companies like Pfizer and Sangamo — which, while behind, have signaled they intend to also pursue accelerated approval for their candidate.

Paul Matteis at Stifel wrote in a July 7 investor note about how such a move “appears firmly within the cards following the well-lit path blazed by BioMarin.”

Boosting Pfizer and Sangamo further are interim Phase 1/2 data that showed patients who received the highest dose of SB-525 were sustaining normal levels of Factor VIII clotting protein. While more data are needed to confirm these responses, Matteis argued that SB-525 appears to be an “authentic competitor” to valrox, particularly in light of the latter therapy’s “so-so” interim Phase 3 data presented thus far.

Valrox’s lead, however, does carry clear advantages.

Cantor Fitzgerald recently surveyed 25 doctors who treated about 3,000 hemophilia A patients in the U.S. and Europe. Results found that, on average, 28% intend to prescribe valrox to eligible patients within two years of its launch, and 39% said they would within five years.