Gene Therapy, Results

#ASH17: Spark triggers a backlash as early hemophilia A gene therapy data looks shaky

Following up on its impressive work on a new gene therapy for hemophilia B, Spark Therapeutics $ONCE has offered a peek at its cards on the early data from a separate program it has on hemophilia A. And it’s clear that there’s a lot of work to be done.

Looking over a tiny group of patients with varying degrees of exposure to the factor VIII gene carrying SPK-8011, investigators tracked a range of responses ranging from single to double-digit responses in factor VIII levels. And coming after some solid data from BioMarin, which has the leading gene therapy program in hemophilia A, investors quickly clipped 33% off of Spark’s share price this morning at the unsteady results it produced.

Two patients getting 5 x 10 (to the 11th) vector genomes registered one with levels that fluctuated between 7% and 11% and another from 6% to 37%, hitting the high number at the cutoff. Two others getting a lower dose more recently saw a mean level of 9% (7 to 12%) and 13% (7 to 24%) of normal.

Katherine High

Significantly, the bleed rate was reduced to zero and there was a 98% reduction in infusion rates. But I asked Spark R&D chief Katherine High about the range of responses and whether that was a concern.

“I’m very pleased that we’re getting a very marked reduction in annualized bleeding rate and no one is taking factor anymore,” says High. It’s also still early days in terms of responses for a dose-ranging study.

“More than 12% and less than 100%,” says High, “that’s the range I’m looking for.”

But it’s not the range they’re getting now.

Compare that to BioMarin, which reported a few days ago that valoctocogene roxaparvovec did this:

Since the last data update provided on Oct. 18, 2017, the three patients with the longest follow-up (at week 48) have Factor VIII activity levels that are in or near to the normal range with both median and mean values of 49%.

BioMarin shares $BMRN are up 8% this morning.

Joseph Schwartz at Leerink did the cross trial comparison and raised BioMarin’s fist for the crowd. Here’s what he had to say about SPK-8011.

Although the enrollment size is small so far (n=5), early signs raise more caution than encouragement, on balance, and lead us to question whether there will be adequate dose-response for patients to reliably achieve normal Factor VIII expression levels.

Still, for Spark, one of the top performers in gene therapy with the first likely US approval looming, it’s a start.

“I’m excited about the results for this kind of work,” High adds. “You always sweat about the starting dose in humans and we went conservative and started at 5 to the 11th. I thought it would be sub therapeutic but that was not correct. The one at 37%, he got the lowest dose.”


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OrbiMed Advisors New York, NY
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Novotech Boston, MA
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Adaptimmune Philadelphia, PA

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