MacroGenics reported on Thursday afternoon that three patients died in a mid-stage trial of its antibody-drug conjugate for prostate cancer. Two participants died due to pneumonitis and the third died from a pleural effusion.
The biotech’s shares $MGNX plummeted 66% to $4.91 premarket on Friday.
A total of five patients died in the trial, although two of the deaths were deemed unrelated to vobramitamab duocarmazine, also dubbed vobra duo. All but one patient in the trial had a treatment-emergent adverse event and 33.5% experienced a grade 3 or higher event.
The Phase 2 TAMARACK trial tested two doses of vobra duo in patients with metastatic castration-resistant prostate cancer who had already received one prior androgen receptor axis-targeted therapy. A total of 176 participants were dosed with MacroGenics’ anti-B7-H3 drug by the April 12 cutoff date, according to a company presentation.
MacroGenics said it is investigating the cause of the three deaths, but will also work on initial steps to prepare for a potential Phase 3 study of vobra duo in 2025.
But Stifel analysts said they struggle to see how vobra duo can differentiate itself on safety, given the patient deaths and the sharp rise in certain adverse events. They wrote that rates of pleural effusion and peripheral edema tripled and more than tripled, respectively, compared with a TAMARACK data abstract published in April. There were no deaths reported in that abstract.
“Safety deteriorated from the abstract which raises material questions,” TD Cowen analysts said, adding they wanted to know more about the timing and nature of the fatalities.
“We are discouraged by the vobra duo update and are shifting our thesis towards the company’s second B7-H3 ADC program, MGC026,” Leerink Partners analysts said.
MGC026 is currently in a Phase 1 dose escalation test in advanced solid tumors. The antibody for MGC026 is site-specifically conjugated to exatecan, a topoisomerase I inhibitor payload developed by Lonza’s Synaffix.
In TAMARACK’s primary endpoint, a quarter of patients given the 2.7 mg/kg dose of vobra duo had an objective response, compared with 17.8% of patients in the 2.0 mg/kg cohort. Of those in the lower dose cohort, 43.9% attained a prostate-specific antigen (PSA) response, defined as a minimum 50% reduction in PSA from baseline.