Stock prices for ADC Therapeutics dropped dramatically by nearly 53% during premarket hours Thursday following concerning results from a major clinical trial of their blood cancer treatment that showed increased patient mortality rates, even though the study achieved its primary effectiveness target of extending progression-free survival.
The large-scale confirmatory trial evaluated ADC’s drug Zynlonta combined with Roche’s antibody treatment Rituxan for patients suffering from relapsed or refractory diffuse large B-cell lymphoma, an aggressive form of blood cancer that rapidly spreads through the lymphatic system.
According to the company’s Wednesday evening announcement, the treatment group experienced 27 deaths representing 13.2% of patients, while the control group receiving Rituxan plus chemotherapy saw only 9 deaths or 4.6% of participants. The company noted that most fatalities in the treatment group occurred among patients who were 75 years old or older.
Guggenheim analyst Michael Schmidt observed that while other measures of effectiveness appeared promising, the elevated death rate in the Zynlonta treatment group overshadowed these positive results.
The U.S. Food and Drug Administration granted Zynlonta accelerated approval in 2021, making this confirmatory study essential for demonstrating clinical benefits necessary for complete U.S. approval.
Company officials stated they plan to conduct meetings with the FDA in August and intend to file a supplemental application during the fourth quarter of this year.
Schmidt commented on the treatment’s market position, saying “The overall value proposition of the combination — which is targeted as a community-friendly & easy-to-administer therapy for patients that are not bispecific antibody candidates — will likely be debated by some investors.”
Zynlonta functions as an antibody-drug conjugate engineered to specifically attack cancer cells while minimizing harm to healthy tissue.
The company explained the elevated mortality rate by pointing to factors including the advanced age of many patients and extended monitoring for adverse events in the treatment group, where participants remained on therapy for longer periods as control group patients frequently switched to alternative treatments early.
Regarding the death rates, Schmidt noted, “While Grade 5 TEAEs (deaths) are generally unfortunately not uncommon in the treatment of DLBCL, most other regimens have single-digit percentage Gr 5 TEAE rates, with higher rates reported due to COVID-19 during the pandemic.”
