Enrollment in a mid-stage clinical study of MacroGenics’ bispecific antibody lorigerlimab has been partially halted by the U.S. Food and Drug Administration after a patient death and multiple serious adverse events. The action affects an ongoing Phase 2 trial evaluating the drug in gynecologic cancers.
The patient who died developed grade 4 neutropenia along with concurrent septic shock, according to the company’s release. Grade 4 events are defined as life-threatening and requiring urgent intervention. In addition to the fatal case, MacroGenics reported three other grade 4 safety events: one instance of myocarditis and two cases of thrombocytopenia.
Before the FDA’s decision, the Maryland-based biotechnology company had already voluntarily paused enrollment in the study after four patients experienced severe neutropenia, myocarditis, and thrombocytopenia. The partial clinical hold now formally suspends new patient enrollment. However, individuals who have already been enrolled are permitted to continue receiving treatment. A total of 41 patients have been dosed to date, out of a planned enrollment of approximately 60.
The Phase 2 trial, known as the LINNET study, is evaluating intravenous infusions of lorigerlimab in patients with platinum-resistant ovarian cancer and clear cell gynecologic cancer. Lorigerlimab is a bispecific antibody designed to target the immune checkpoint proteins PD-1 and CTLA-4. By acting on both pathways, the therapy is intended to boost anticancer immune activity and prevent malignant cells from evading immune detection.
MacroGenics has also been studying lorigerlimab in other indications. The company previously conducted a mid-stage trial in metastatic castration-resistant prostate cancer but discontinued that program at the end of last year. In addition, a Phase 1 study of the drug is ongoing in patients with unresectable or metastatic advanced solid tumors.
In a prepared statement, Eric Risser, president and chief executive officer of MacroGenics, said: “At MacroGenics, our top priority is patient safety.” He added that the company is fully committed to working closely with the FDA to resolve the partial clinical hold and intends to resume study enrollment as soon as possible.
According to a Feb. 24 note from analysts at Leerink Partners, MacroGenics management indicated that the company plans to submit a response to the FDA within days or weeks. The response is expected to include updates on the outcomes of the reported safety events, discussions from data monitoring committee meetings, and potential modifications to eligibility criteria and safety monitoring procedures. After the submission, the FDA will have 30 days to respond. Analysts noted that company leadership hopes the hold can be resolved within that period.
The news prompted movement in the company’s share price. MacroGenics’ stock declined from a previous close of $1.75 to $1.60 at market open on Tuesday, representing a drop of about 8%. During early trading, shares fell as low as $1.55 before recovering. By the close of Tuesday’s session, the stock finished at $1.73, regaining much of the earlier decline.
The safety-related pause follows prior setbacks for the company. In 2024, five patients with advanced prostate cancer died during a Phase 2 study of MacroGenics’ B7-H3-directed antibody-drug conjugate, a program that has since been discontinued.
What Led to the Partial Hold
MacroGenics reported serious safety events in four patients, including one death due to septic shock linked to severe neutropenia, prompting FDA action.
Status of the Lorigerlimab Trial
Enrollment of new patients is stopped, but participants already in the study may continue treatment under close monitoring.
While new patients can no longer be enrolled, current participants may continue receiving lorigerlimab under ongoing oversight. MacroGenics has stated that patient safety is its top priority and that it is collaborating closely with the FDA to resolve the partial clinical hold and resume enrollment as soon as it’s safe to do so. ﹘
The news of the partial hold has also weighed on MacroGenics’ stock performance as investors react to the regulatory setback and uncertainties surrounding the lorigerlimab program’s timeline and safety profile. ﹘
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