Roche targets 2021 start for hemophilia A gene therapy phase 3 as optimization effort drags on

Roche has posted updated clinical data on a hemophilia A gene therapy it acquired in its $4.3 billion takeover of Spark Therapeutics. The study linked SPK-8011 to improvements in factor VIII expression and bleeding out as far as 3.3 years after administering the therapy, but, with Spark still optimizing the regimen, it will be 2021 before phase 3 dosing begins.

Spark is well behind BioMarin in the race to get a hemophilia A gene therapy to market in the U.S. While BioMarin is waiting on a decision from the FDA, Spark is still figuring out the optimal dose and immunomodulatory regime for its phase 3 trial. Spark started a lead-in study for its phase 3 last year, but it will be 2021 before dosing commences. By then, BioMarin’s valrox may be approved, and Pfizer and Sangamo Therapeutics will likely have begun dosing in a phase 3 trial of their challenger SB-525.

Roche and Spark used the International Society of Thrombosis and Hemostasis 2020 Virtual Congress to make the case that SPK-8011 can carve out a space in the competitive market. By early June, Spark had two to 3.3 years of follow-up on 12 patients treated with SPK-8011. The trial linked SPK-8011 to a 91% reduction in annualized bleed rate and a 96% drop in factor VIII infusions.

With factor VIII expression holding steady, the phase 1/2 study suggests SPK-8011 delivers durable improvements in hemophilia A patients. However, the previously disclosed failure of SPK-8011 to trigger lasting improvements in factor VIII expression in two patients continues to cast a shadow over the clinical trial. Shares in Spark fell 30% when it revealed the failures late in 2018.

Spark attributed the failures to a capsid-based immune response. Five of the nine participants to get the high dose of SPK-8011 received daily oral steroids in response to suspected immune responses against the capsid. Two of the five participants lost factor VIII expression.

The immunogenicity concerns are contributing to the wait for SPK-8011 to start phase 3. Specifically, researchers are studying alternatives to daily dosing of oral steroids as part of their effort to optimize vector dose and immune suppression regimens. The goal is to hit upon an approach that yields safe, predictable and durable increases in factor VIII expression.

While Spark works through those problems, BioMarin is preparing for commercial sales of valrox, and Pfizer and Sangamo are gearing up for the fast-approaching start of a phase 3 trial of a gene therapy that looks very competitive based on limited data.