- Roche subsidiary Spark Therapeutics announced it will begin dosing its hemophilia A gene therapy SPK-8011 in a Phase 3 trial next year, following the completion of an ongoing "run-in" study that's designed to establish a baseline for evaluating the treatment's effect on bleeding frequency.
- The disclosure came as the Philadelphia-based gene therapy developer gave its first look since December 2018 at data from early-stage trials of SPK-8011. The previous update was followed shortly thereafter by Roche's takeout bid, which was held up for months while U.S. antitrust regulators reviewed the transaction.
- Roche and Spark could be well behind BioMarin's gene therapy Roctavian, which is due to receive a Food and Drug Administration decision on approval by Aug. 21.
Gene therapy has the potential to transform hemophilia treatment by allowing patients to wean themselves off of chronic and expensive factor replacement therapies, which are required to prevent potentially life-threatening bleeding episodes.
Should the FDA approve BioMarin's Roctavian in the coming weeks, it could become the most expensive per-dose drug ever launched, possibly exceeding the $2.1 million set by Novartis for its gene therapy Zolgensma. But BioMarin has argued that Roctavian would be well worth a large expense because it could save the healthcare system from covering millions of dollars worth of other hemophilia drugs.
At one time, Spark looked to be close behind BioMarin. However, Spark suffered some setbacks in early-stage development. Doctors and patients then heard little about the program for more than a year while the Roche transaction was under way.
The new data on SPK-8011, which include longer follow-up on trial participants, were detailed at the virtual meeting of the International Society on Thrombosis and Haemostasis. Fourteen patients have received one of three doses of SPK-8011, one of whom was first treated more than three years ago.
Bleeding episodes per year have been reduced by 91% — one patient has an annualized bleeding rate of zero —and factor replacement therapy use has been reduced by 96%. Though caveats apply when comparing treatments across trials, the results look to be roughly on par with Roctavian, which in a Phase 3 study reduced mean annual bleeding rates to 1.5 in a group of 16 patients, an 85% reduction, and factor replacement therapy use was reduced 94%.
But safety and variability in patient responses have been issues for SPK-8011. Steroids are used to tamp down an immune response to gene therapy administration, and Spark disclosed two new cases of mild steroid-related side effects. That adds to three earlier cases of elevated liver enzymes, one of which caused a patient to be hospitalized.
Two patients who have been dosed with the gene therapy stopped responding, which is suspected to be the result of an immune response to the virus used to shuttle the genetic material into the body. Spark previously disclosed the information.
Before determining how it will treat patients with SPK-8011 in a Phase 3 trial, Spark said it is still working to identify the "lowest effective dose and the optimal immunomodulatory regimen," Federico Mingozzi, Spark's chief scientific officer, said in a statement.