Gene Therapy

Spark carefully records a safe step forward for closely-watched hemophilia gene therapy

CEO Jeff Marrazzo

Four months after rattling investors with evidence of an immune reaction to its gene therapy, Spark Therapeutics $ONCE is updating its data on the Phase I/II study of its hemophilia B treatment, offering fresh evidence that researchers were able to resolve the issue without losing the treatment effect.

Spark also noted that with all 10 patients past at least 12 weeks of therapy — and two past the one-year mark — the once-and-done approach to hemophilia had almost — though not quite — wiped out infusions for the group. And the annual bleed rate was cut 96%.

Researchers reported a variable response to the treatment, but were happy with a steady-state factor IX activity level after 12 weeks treatment for the 10 participants — up one from the last update — at a sustained 33% (range as of the data cutoff: 14% to 81%).

The annualized bleeding rate was reduced by 96% to a mean of 0.39 annual bleeds, compared with 9.2 bleeds before SPK-9001 administration. The infusion rate was slashed 99%, cut to one compared with 68.5 infusions before SPK-9001 administration.

Spark is the leader in a group of gene therapy biotechs steering these pioneering therapies through clinical studies. And their updates are significant milestones, providing the first track record for therapies that offer patients a potential cure.

Spark’s therapy hasn’t been perfect. One of the 10 patients, as we already know, received an infusion of Factor IX to deal with a suspected knee bleed. And two have seen liver enzymes spike, indicating an immune reaction to the delivery vehicle used for the therapy. Both of those cases were dealt with by steroids, and CEO Jeff Marrazzo was quick to highlight the significance.

“We’ve shown evidence that we can manage immune response with steroids,” he says, with one of those patients now off steroids for 9 weeks. “The fact that we cracked that is not only critical to this program, it gives you different visibility of putting genes into the liver as a means of providing a therapy.”

What may look like a relatively small problem for some therapies tend to loom large for gene therapy. These therapies will be attached to some stunning prices, and payers are going to look for assurances that they are going to get the cures they’re paying for.

Leerink’s Joseph Schwartz considers the update a relatively small positive for Spark, he was left looking for more insight.

Today’s PR highlights that these issues were resolved after a tapering course of steroids, but two issues still remain. First, it is unclear how physicians can preemptively identify pts. with a greater likelihood of mounting an immune response to Spark100 capsid/SPK-9001 and therefore initiate steroid therapy without sacrificing FIX activity. Secondly, with SPK-8011 in hemophilia A representing a larger mkt. oppty (plus SPK-8011 is unpartnered), how exactly SPK-9001’s experience (Spark100) could provide read-through to SPK-8011 (Spark200), which is set to announce the first Ph.1/2 data in mid-2017, remains unclear.

This first group of patients will be followed for years. And Marrazzo says Spark may add more patients to the study, depending on what its partner, Pfizer, wants to see for its Phase III trial. Planning for that study is well under way.

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