BioMarin seeks haemophilia gene therapy approval after promising data


BioMarin is set to file for approval for its haemophilia gene therapy valoctocogene roxaparvovec, after it achieved pre-specified clinical criteria for regulatory review.

The company said that the data show that a single dose of valoctocogene roxaparvovec should stop the spontaneous bleeding of people with haemophilia A for at least eight years.

However the trial only tested a small group of patients who have at most been on the treatment for three years.

Data also suggest that the treatment’s ability to produce the blood-clotting protein Factor VIII declines after four months but then plateaus around the three-year mark.

This three-year data did not meet some analysts’ expectations, but others were more optimistic.

SVB Leerink analyst Joseph Schwartz said: “We believe plateauing of declining Factor VIII is reassuring and the data appears stronger than what we or investors largely assumed.”

In any case, BioMarin now intends to meet with the Food and Drug Administration (FDA) and European Medicines Agency (EMA) to review the phase 3 data and the other elements of a submission and intends to announce the timing for its planned marketing applications in Q3 2019.

The therapy has been granted Breakthrough Therapy Designation by the FDA and Priority Medicines (PRIME) status by the EMA.

As of May 28, 2019, eight patients in the 20-patient cohort of the Phase 3 GENEr8-1 study achieved Factor VIII levels of 40 international units per deciliter (IU/dL), or more, at 23 to 26 weeks, meeting the pre-specified criteria for Factor VIII activity levels.  

For the 16 patients who had reached week 26 by the April 30 cutoff since administration of valoctocogene roxaparvovec, the estimated median Annual Bleed Rate (ABR) was zero and the estimated mean ABR was 1.5, representing a reduction of 85% from baseline levels where all patients were on standard of care prophylaxis.

In addition, there was an 84% reduction in median annualised Factor VIII usage and a 94% reduction in mean FVIII usage annualised between week 5 and 26.  In the 23 to 26 week time period the mean Factor VIII level using the CS assay was 36 (SD=28) IU/dL and the median was 33 IU/dL.

Hemophilia A is usually treated with two to three self-injections a week – meaning a one-time gene therapy could be a game-changer for these patients.

Pfizer and Spark Therapeutics are among the other companies chasing one-time haemophilia treatments – although Spark’s therapy has been dogged by safety concerns.