Pfizer reveals delays across the board for its clinical gene therapy programs
At JP Morgan 2020, a year after taking the reins at Pfizer, Albert Bourla claimed the company was poised to become a leader in gene therapy. He’s since thrown hundreds of millions of dollars at those plans, including a $630 million deal just last month for two of Voyager’s AAVs.
Now, it appears Phase III readouts are further away than Bourla had hoped.
Setbacks have resulted in delays across all three of Pfizer’s clinical gene therapy programs, the company revealed in its Q3 results on Tuesday — including one trial which was paused over safety concerns.
Pfizer’s slamming the brakes on its Sangamo-partnered Phase III hemophilia A study after some patients reported high levels of Factor VIII, an essential blood-clotting protein. Normal Factor VIII levels typically range from 50% to 100%, and anything lower than 50% could indicate hemophilia A. However, levels above 150% are associated with an increased risk of thrombosis, or the formation of clots in the blood vessels.
Multiple patients in Pfizer’s hemophilia A trial had Factor VIII levels over 150%, though the company has not said how many. To date, no patients have experienced thrombotic events, and some are being treated with oral anticoagulants to reduce the risk, Pfizer said.
The company says it has voluntarily halted screening and dosing in the study — which is more than half-full — until it can amend the protocol to provide guidelines for the management of elevated Factor VIII levels.
This isn’t Pfizer’s only hemophilia setback. Separately, the company said, “recent interactions with the FDA” have led it to decide against conducting interim analyses for both its hemophilia A and B studies. Instead, it will wait for full analyses based on at least 50 participants in the hemophilia A study and 40 participants in the hemophilia B study, pushing out the timelines for both of the programs.
While Pfizer had been anticipating readouts in 2022 for its hemophilia B and A programs, it is now looking at a Q1 2023 readout for hemophilia B. The company hasn’t provided a new timeline for the hemophilia A program.
That could put Pfizer significantly behind its rival uniQure, which read out some positive Phase III results from a 54-patient trial back in June. Over the course of a 52-week period, uniQure’s drug reduced patients’ annualized rate of bleeding requiring treatment by 80% from baseline. That trial was briefly put on hold in December following the diagnosis of HCC in one patient, but regulators gave uniQure the OK to resume in April.
uniQure says it plans to submit a BLA in the first quarter of next year.
Pfizer’s also expecting a delay in its pivotal DMD study, which is now expected to read out in 2023. The news comes after safety concerns led Pfizer to scale back that trial, cutting out patients with certain genetic mutations.
Three cases of muscle weakness, two of which included heart inflammation, forced the trial amendment. In its Q3 results, Pfizer said it’s believed that an immune response against the mini-dystrophin protein caused these cases. All patients were treated with higher doses of steroids, and all improved within a few weeks, though some are still recovering.
“This type of reaction is a risk potentially inherent to any gene replacement therapy, and similar severe adverse events reported in other programs support the notion that this is a class effect,” Pfizer said.
This isn’t the first time the DMD program has hit a roadblock on its late-stage path, with the company reporting in May that it was meeting headwinds from the FDA on the quality of its potency assays.