The FDA has ordered MacroGenics to halt enrollment in a phase 2 trial of the biotech’s lead candidate lorigerlimab following severe side effects that led to one patient’s death.
Maryland-based MacroGenics had already voluntarily paused enrollment in the trial, the biotech said in a Feb. 23 release, following four patients experiencing severe thrombocytopenia, myocarditis and neutropenia. The patient who died experienced neutropenia, a term for critically low levels of white blood cells called neutrophils, and subsequent septic shock, according to the release.
The phase 2 trial is testing infusions of lorigerlimab, a bispecific antibody targeting the immune checkpoints PD-1 and CTLA-4, for platinum-resistant ovarian cancer and clear cell gynecologic cancer. Forty-one patients have been dosed thus far, MacroGenics said in the release, out of a planned total enrollment of around 60. Patients already enrolled in the study will continue to receive treatment.
“At MacroGenics, our top priority is patient safety,” Eric Risser, the company’s president and CEO, said in the release. “MacroGenics is fully committed to working closely with the FDA to resolve the partial clinical hold and we intend to resume study enrollment as soon as possible.”
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The clinical hold is another blow for lorigerlimab, which MacroGenics already dropped in prostate cancer at the end of last year.
In a Feb. 24 note, analysts from Leerink Partners wrote that they spoke with MacroGenics management about the hold and were told the company plans to submit a response to the FDA “in a matter of days or weeks.”
The biotech’s response “will include follow-up on safety event outcomes, data monitoring committee meetings, as well as potential changes in eligibility criteria and safety monitoring,” the analysts wrote. After a response is submitted, the FDA will have 30 days to respond, and MacroGenics leaders “hopes that this partial clinical hold will be resolved within that period,” according to the analysts.
MacroGenics’ share price dipped from yesterday’s high of $1.78 to $1.55 at the opening of today’s trading, but has since rebounded to $1.70 per share as of Tuesday afternoon.
The antibody outfit is no stranger to safety woes. In 2024, five patients with advanced prostate cancer died in a phase 2 study of MacroGenics’ B7-H3-directed antibody-drug conjugate, which the company has since discontinued.
