- Spark Therapeutics Inc. looks set to soon become the first to launch a gene therapy for an inherited disorder in the U.S. Yet that mattered little to investors Monday, when shares in the biotech fell by 35% on mixed data for the company's experimental treatment for hemophilia A.
- While Spark's hemophilia gene therapy has so far largely eliminated bleeding in four treated patients, Factor VIII activity levels were disappointing and unexpectedly inconsistent. Two of the four were given steroids after seeing their Factor VIII activity drop post-infusion.
- Spark suffered by comparison to BioMarin Pharmaceuticals Inc, which on Saturday reported its rival gene therapy boosted Factor VIII levels to normal or near-normal in 11 of 13 patients with hemophilia A.
This year's annual meeting of the American Society of Hematology showcased encouraging therapeutic advances in hemophilia, beginning with updates on Roche AG's newly approved Hemlibra (emicizumab) and impressive early data on BioMarin's hemophilia A gene therapy valoctocogene roxaparvovec.
Unfortunately for Spark, its own progress lost some of its shine in comparison. Mean Factor VIII activity in the four patients treated with Spark's hemophilia A gene therapy SPK-8011 ranged from 9% to 16% after Day 84. Three more patients have been treated, with two on a higher dose, but the data from the first four showed no clear dose response relationship.
Activity levels also appeared unpredictable, rising to above 25% in one patient before falling to below 10%.
Spark expects to update the data in the second or third quarter of next year. In the bull case, laid out by Jefferies analyst Michael Yee in a Dec. 11 note, that update could still show more competitive activity and improved consistency. But in Yee's bear scenario, the variability seen in the first four patients remains unexplained and Spark has a longer road to restoring confidence.
Spark's prospects look better in hemophilia B, where data updated last week in The New England Journal of Medicine showed sustained — and predictable — levels of Factor IX following treatment with another of the biotech's gene therapy candidates, called SPK-9001. All 11 patients have discontinued routine infusions of Factor IX concentrate, with the average annualized number of bleeds cut to almost zero.
"It just looks fantastic," said Michael Callaghan, pediatric hematologist-oncologist and assistant professor of pediatrics at Wayne State University, in an interview. "It's only an early phase study, but they're getting very good levels in the 20% to 50% range."
Spark plans to enroll up to four more patients into its study to further test a new manufacturing process and then will hand the clinical development reins over to Pfizer Inc., which is partnered on SPK-9001.
Hemophilia B, a rarer variant than hemophilia A, is considered a better focus for gene therapy due to the smaller size of the gene that encodes for Factor IX production. But the results from BioMarin have turned that thinking on its head and brought closer the possibility of a one-time treatment in hemophilia A as well as B.
For Spark, now trailing in hemophilia A, a nearer term catalyst could come early next year if the Food and Drug Administration approves its experimental gene therapy for an inherited form of childhood blindness. An OK looks likely, and would make Spark the first to win approval for a gene therapy for a hereditary disorder.