Gene Therapy, Results

Spark Therapeutics offers a glimpse of efficacy in first two hemophilia A gene therapy patients

With its lead gene therapy under FDA review, Spark Therapeutics $ONCE is now unveiling the first encouraging responses on the hemophilia A front.

Jeffrey Marrazzo

With analysts looking for a 12%-plus Factor VIII response, the company says that investigators tracked an 11% and 14% stabilized rise in Factor VIII activity in the first two patients who were given the therapy in the dose-escalation study.

Key to this part of the process, researchers say they have seen no Factor VIII inhibitors appear, no thrombotic events, no spontaneous bleeds and no need to use corticosteroids on the patients, who have been tracked for 23 and 12 weeks.

As a result, the biotech says that it has now doubled the dose and treated the third patient in the proof-of-concept study. States the company: “While the results for this third participant are early, his factor activity level is tracking proportionally higher, consistent with the dose escalation.”

Spark shares surged 15% this morning as the biotech updated the data as well as its Q2 results.

Noted Jefferies’ Michael Yee recently: “First data from Phase I/II of Hemophilia A gene therapy SPK-8011 in July/Aug could establish early proof-of-concept and be a (+) catalyst. Given small no. of pts to start, key is demonstrating potential to get to 12%+ Factor VIII.”

Spark Therapeutics is the most advanced biotech in the US gene therapy field, with a good chance to win the first ever FDA approval for a once-and-done treatment. As a result, analysts are watching every step CEO Jeff Marrazzo makes. The biotech has been making steady progress with a gene therapy for hemophilia B after getting over some early safety jitters. And just days ago Spark was handed a priority review of its lead program for RPE65-mediated inherited retinal disease, putting it first in line for a US approval.

To be sure, Spark isn’t alone in hemophilia A. Sangamo has a program underway. But the leader in this field is BioMarin $BMRN, which has produced some stellar – though also puzzling — results. Now ready to go into Phase III, early-stage studies demonstrated a wide variability in Factor VIII expression needed to keep hemophilia in check. Joseph Schwartz at Leerink has noted that investors will look closely to see if regulators are concerned by the much-higher-than-normal levels of Factor VIII in some patients before approving the Phase III design. In the meantime, look for some careful examination of stability versus high but variable impact.

Once over the finish line, gene therapies will present payers with a thorny issue. How do you cover therapies that have the promise of being used just once, without any guarantees that they can last a lifetime? Prices are expected to be sky high, which has held back the two gene therapies that have been approved in Europe, though only rarely used.

Katherine High

“The encouraging start of our SPK-8011 clinical trial reinforces the strength of our gene therapy platform, delivers human proof-of-concept in a second liver-mediated disease — a significant achievement in the gene therapy field — and positions us well to potentially transform the current treatment approach for this life-altering disease with a one-time intervention,” said Katherine High, president and chief scientific officer of Spark Therapeutics. “We are excited about the progress we are making to achieve our goals of our investigational hemophilia A and B programs: to safely achieve predictable, consistent and sustained activity levels that prevent spontaneous bleeding.”


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RAPS Regulatory Convergence 2017