- An experimental gene therapy developed by BioMarin Pharmaceutical eliminated spontaneous bleeding and restored activity of a blood clotting protein to normal or near-normal levels in patients with hemophilia A through two years of treatment, according to an update from the company on Tuesday.
- Presented at the 2018 meeting of the World Federation of Hemophilia, BioMarin's results reinforce the potential of the one-time treatment and, importantly, showed no warning signs of major safety concerns such as inhibitors to Factor VIII clotting protein.
- Also on Tuesday, Spark Therapeutics and big pharma partner Pfizer unveiled updated data that showed all 15 hemophilia B patients treated with the biotech's gene therapy had stopped receiving routine infusions of Factor IX.
Taken together, the updated results from BioMarin and the team of Spark and Pfizer underscore the growing momentum behind hemophilia gene therapies, which hold out the promise of transforming how the blood disorder is treated.
For gene therapies in particular, durability of efficacy and continued tolerance of the one-time treatments are key questions that drugmakers need to answer. On that score, Tuesday's updates should help build confidence in the emerging profile of the two treatments.
BioMarin's data, which extends through two years of follow-up, showed treatment with a high dose of its valoctocogene roxaparvovec reduced mean annual bleeding rates in hemophilia A patients by 97%. Nearly 90% of patients had zero bleeds requiring Factor VIII infusions in year two of treatment — a dramatically higher proportion than the 14% who avoided such bleeds in a year at baseline.
A lower dose showed a similarly impressive, although slightly less dramatic, benefit over the first year of treatment.
No patients withdrew from treatment and therapy was generally well tolerated. Seventy-three percent of patients on both doses experienced transient elevation of liver enzymes, which were reversed. Two individuals experienced serious adverse events, although only one was deemed related to valoctocogene roxaparvovec.
BioMarin is studying both a high and low dose of its treatment in Phase 3 studies. The company now plans to increase enrollment in its trial of the high dose to 130 participants, with the aim of demonstrating superiority over Factor VIII infusions.
The study is expected to fully enroll by the first quarter of 2019, BioMarin said.
Investors, however, didn't appear as enthused, sending shares in the company down by 5% in Tuesday morning trading. Commentators on Twitter speculated that a leveling off of Factor VIII activity by the end of two years in patients treated with the high dose could be behind the sell-off.
"While Factor VIII levels have waned somewhat from one year to two years and is likely the reason for the share weakness this morning, [BioMarin] remains optimistic that levels have stabilized based on preclinical models," noted Evercore ISI analyst Josh Schimmer in a May 22 note.
For Spark, which took a back seat to BioMarin in hemophilia A at last year's ASH conference, the results released Tuesday appear to strengthen the case for its experimental hemophilia B treatment.
Average annual bleeding rates dropped 98% to 0.2 per year, compared to a rate of 8.9 bleeds prior to treatment based on individual patient history. Six individuals received Factor IX infusions after being given Spark's candidate, of which two were for reported spontaneous bleeds.
No patient experienced serious adverse events, thrombotic events or developed inhibitors to Factor IX.
According to Spark, all 13 patients with 12 weeks of follow-up after treatment infusion reached stable Factor IX levels of more than 12%.
Spark will transition the Phase 1/2 study over to Pfizer later this year, and plans to deliver a batch of drug substance to enable the pharma to begin Phase 3 testing of the candidate.
As both treatments move into later-stage clinical testing, the conversation around hemophilia gene therapies has begun to turn more toward potential pricing if these treatments ever reach market.
A note from Leerink analyst Joseph Schwartz earlier this month suggested the treatments could command prices over as much as $1.5 million, noting that the current high annual costs of treatment could provide a floor.
"This may sound bold as it breaks the seemingly impervious $1M threshold for drug price; however, payers' extensive experience with factor replacements (economically and clinically) could tip the payers to be more flexible in accommodating an expensive hemophilia gene therapy as long as the safety and efficacy profile is supportive," wrote Schwartz.
Shares in Spark rose by little more than 1% Tuesday.