ADC Therapeutics shares sink over 50% after Phase 3 Zynlonta trial shows more deaths than standard therapy

ADC Therapeutics shares plunged more than 50% after a Phase 3 trial of its lymphoma drug Zynlonta (loncastuximab tesirine) showed more deaths in the treatment arm than in the control arm, despite meeting the trial's main efficacy endpoint.

In the LOTIS‑5 confirmatory trial in relapsed/refractory diffuse large B‑cell lymphoma (DLBCL), 27 deaths were recorded among patients receiving Zynlonta plus rituximab compared with 9 deaths in the immunotherapy control arm, spooking investors and raising regulatory concerns.

The company noted that most excess deaths occurred in older, frailer patients (often aged 75 or above), and reiterated that there is no statistically significant detrimental effect on survival, but the higher mortality and adverse event rate have cast doubt on Zynlonta's full approval path.

Safety data also show a higher rate of serious adverse events with Zynlonta vs control (around 49% vs 34.5%), including serious infections and hepatotoxicity, consistent with the drug's known safety profile that already includes warnings for fatal infections and drug‑induced liver injury.