An early clinical update on Pfizer’s Duchenne muscular dystrophy (DMD) gene therapy has raised safety concerns. One of the first six people to receive the treatment was hospitalized with acute renal injury, leading analysts to talk down Pfizer’s chances of competing with Sarepta.
Pfizer expected to see immune responses in patients who received AAV9 gene therapy PF-06939926. In five patients, the reactions didn’t escalate to immune-related clinical events. However, one patient suffered a rapid antibody response with activation of the complement system associated with acute kidney injury, forcing the physician to admit them to an intensive care unit.
The subject left the hospital 11 days later having received intermittent hemodialysis and two intravenous doses of a complement inhibitor. Renal function returned to normal within 15 days.
Pfizer responded to the adverse event by stopping dosing in the phase 1b trial. Work is underway to put additional safety monitoring in place so Pfizer can resume dosing of the last six DMD patients it plans to treat in the study.
The kidney complication that led Pfizer to pause the study was one of a number of adverse events seen in the trial. Another subject was hospitalized for two days to receive intravenous antiemetics and replacement fluids to treat nausea and vomiting. Three other subjects suffered those symptoms but were managed with oral antiemetics.
More positively, Pfizer emerged from the early readout with evidence that PF-06939926 works. Bicep biopsies taken two months after treatment detected minidystrophin immunofluorescence signals, with a mean of 69% positive fibers in subjects who received the 3E14 vg/kg dose. That level of efficacy could be clinically significant.
Sarepta’s gene therapy achieved mean microdystrophin levels of 74% of normal last year, although its use of a different technique for measuring the protein makes it hard to compare the two results.
Even so, the lack of a clear efficacy edge, safety concerns and trial delay were enough to lead analysts to downplay the chances of Pfizer competing with Sarepta. William Blair analyst Tim Lugo called Sarepta the “clear leader in DMD with no close No. 2” after getting a look at the Pfizer data. With other analysts making similar comments, shares in Sarepta closed up 17%.
Lugo’s claim that there is no close challenger to Sarepta follows a period in which Pfizer and Solid Biosciences’ gene therapies have suffered separate safety scares. However, there remains scope for the current running order to change. Sarepta may be unable to build on its promising early data, or one of its many rivals, such as Vertex, could post results that surpass its performance.