Pfizer's DMD gene therapy looks good in data refresh, but safety concerns persist

Pfizer building
Although the side effects were serious, they were “manageable,” so Pfizer is moving full steam ahead with a phase 3 study slated for the second half of this year. (Tracy Staton)

Pfizer’s gene therapy may have boosted dystrophin levels in a small Duchenne muscular dystrophy study, but safety questions could give Sarepta’s competing treatment the advantage.

Both doses of the gene therapy, PF-06939926, increased the levels of dystrophin in patients’ muscles and improved their scores on the North Star Ambulatory Assessment (NSAA) rating scale, a measure of muscle function in children with Duchenne, according to phase 1b data presented on Friday at the virtual meeting of the American Society of Gene & Cell Therapy.

One year after treatment, six patients—three who received the low dose and three who received the high dose—improved a mean of 3.5 points on the 17-point NSAA scale. Patients in the low-dose group logged dystrophin levels that were 24% of normal and patients in the high-dose group had levels that were 51.6% of normal.

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Pfizer last reported data for the treatment last July, noting that two patients had to be hospitalized due to side effects. One patient needed anti-vomiting drugs and fluids to treat dehydration from vomiting, while the other needed dialysis and the immunosuppressive drug Soliris for acute kidney injury and complement activation, a type of innate immune response. The latest data add a third hospitalization—the patient needed a platelet transfusion and Soliris to remedy a low platelet count and complement-linked side effects.

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Although the side effects were serious, they were “manageable,” so Pfizer is moving full steam ahead with a phase 3 study slated for the second half of this year. The company has already beefed up “monitoring and management regimes” in the phase 1b study, which helped it address the third patient’s side effects quickly, the company said in a statement.

Pfizer is chalking those immune side effects up to the adeno-associated virus used to deliver the treatment, wrote RBC Capital Markets analyst Brian Abrahams in an investor note on Friday, noting this issue could give Sarepta’s gene therapy, SRP-9001, an upper hand.

“This aligns with our view based on the totality of historical data that SRPT’s AAVrh74 vector may have intrinsic safety advantages over AAV9 based approaches, which will give SRPT an advantage both in clinical trials and in the commercial setting, even if PFE’s AEs are ultimately monitorable/manageable,” Abrahams wrote.

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Pfizer’s program isn’t the only one running into safety issues—Solid Bio’s Duchenne gene therapy has been under a partial FDA hold since November after the company reported side effects in a sixth patient, including decreased red blood cell and platelet counts, acute kidney injury and complement activation.

“Although PFE looks slightly more competitive than SLDB, we believe that today's update from PFE further reinforces Sarepta's competitive position on safety since we would have seen evidence of complement issues by now if they were occurring with SRP-9001 since these events happen early post-treatment,” wrote Cantor Fitzgerald analyst Alethia Young in a note.

Young said that monitoring and treating side effects may not cut it—especially in a pandemic.

“[We] think complement activation is a significant hurdle for this program to overcome going forward if SRP-9001's safety and efficacy profile holds up,” Young wrote.

“[Even] if risk can be reduced with high dose steroids or Soliris pretreatment, this may not be viable in the real world. In light of COVID-19, we wonder the comfort level around even a small potential risk of complement activation and having to possibly be hospitalized for no matter how short,” she added.