1-year data set Spark/Pfizer on track with hemophilia B gene therapy

illustration of red blood cells in blood vessel
An NEJM editorial points to a "renaissance" in gene therapy.

Patients with hemophilia B have seen their symptoms controlled for up to a year with a single dose of a gene therapy developed by Spark Therapeutics, almost entirely eliminating the need for treatment with clotting factors.

Over the course of the almost yearlong trial, nine of 10 patients treated with Spark’s SPK-9001 experienced no bleeding episodes after the gene therapy was administered, a 97% reduction in the annualized bleeding rate, and eight patients needed no subsequent factor IX infusions.

The updated results from the phase 1/2 trial of the Pfizer-partnered therapy—just published in the New England Journal of Medicine (NEJM)—have been hailed as an “important milestone” for patients with hemophilia B and evidence of a “renaissance” in gene therapy in an editorial authored by Matthew Porteus, M.D., Ph.D., of Stanford University, an expert in genetic diseases of the blood.

Patients in the study achieved factor IX levels of around one-third of normal concentration ranges, within a range of 14% to 81%, raising the prospect of doing away with the need for infusions every few days to “prevent spontaneous, potentially life-threatening bleeds and to protect their joints,” said Katharine High, M.D., Spark’s head of R&D, in an announcement. Factor IX activity gains of just 5% to 10% are thought to trigger clinical benefits.

The editorial suggests that savings of up to $200,000 per patient per year could come from the use of gene therapy over clotting factor infusions. Moreover, it welcomes the finding that two patients who developed immune-response related side effects were able to have the reaction quickly curbed by using steroid drugs, but says more long-term follow-up data is needed on the durability of the response and safety.

Preliminary results from the study were reported at last year’s American Society of Hematology (ASH) meeting, but the extended follow-up data suggests that SPK-9001 has “remarkable and positive efficacy and safety,” analysts at Jefferies said in a research note, adding that the NEJM editorial “speaks to the notable good things going on in gene therapy [for] hemophilia.”

The results are another dose of good news for Spark as it waits for the FDA’s verdict on its marketing application for Luxturna, its gene therapy for biallelic RPE65-mediated inherited retinal dystrophy, an inherited form of blindness. Luxturna got unanimous backing from an FDA advisory committee in October and is headed for a decision in January.

Despite the positive news flow, some investors have been a little nervous about Spark due to concerns such as manufacturing issues for Luxturna, anxiety about the results of a soon-to-report trial of hemophilia A gene therapy candidate SPK-8011 and comments from a competitor on levels of neutralizing antibodies. Jefferies says these concerns are “overblown and are not fundamentally problematic to [Spark’s] programs.”

Spark is vying with other companies including UniQure, BioMarin, Sangamo and Dimension Therapeutics to bring the first gene therapy for hemophilia to market. Spark and UniQure have emerged as front-runners, particularly after Shire scrapped a hemophilia B candidate developed by Baxalta last year.

The biotech recent rejigged its agreement with Pfizer to allow five additional patients in the phase 1/2 trial to be treated with SPK-9001, and the trial will complete 12 months after the last patient is dosed. Meanwhile the SPK-8011 program is expected to continue to dose more patients in the coming months and move forward to phase 3 by 2019, the analysts note.