ADC Therapeutics said its blood cancer drug met the main goal of a confirmatory trial, but the experiment recorded more deaths among patients treated with the drug, sending shares down more than 50% Thursday morning.
The Switzerland-based company unveiled data from its Phase 3 trial testing an antibody-drug conjugate called Zynlonta in combination with the medicine rituximab among people with a type of hard-to-treat blood cancer. The pairing extended progression-free survival in trial participants compared to a standard treatment combination, meeting the study’s primary endpoint.
But the results were overshadowed by the number of deaths in the study, leaving investors to question the drug’s chances of gaining full approval. The Food and Drug Administration granted accelerated approval to Zynlonta in 2021 based on the results of a trial in which it wasn’t compared to a placebo.
“Given other available options to patients,” the number of deaths “may be difficult to accept for physicians, patients and regulators,” wrote RBC Capital Markets’ analyst Leonid Timashev in a note Thursday.
Zynlonta, used to treat large B-cell lymphoma in people whose disease hasn’t responded to at least two treatments, is ADC’s only asset.
The Phase 3 trial paired the drug with rituximab and tested it against an immunotherapy cocktail of rituximab plus the chemotherapy drugs gemcitabine and oxaliplatin across 440 participants.
ADC’s treatment extended progression-free survival by 1.4 months, with enrollees receiving Zynlota surviving 6.1 months without progression compared with 4.7 months for those on the immunotherapy regimen, a statistically significant difference. The company did not meet its secondary endpoint for overall survival, but said there was “no detrimental effect” on that measure.
However, 27 deaths were recorded for those given Zynlonta, compared to the nine deaths recorded for the immunotherapy arm. The company noted a majority of deaths occurred in patients aged 75 years or older.
Eric Schmidt, from investment firm Cantor Fitzgerald, wrote in a client note that while the death total is likely to “temper both investors' and physicians' views towards these results,” there are some explanations for why the rate was higher than what was previously seen for Zynlonta.
Schmidt explained that the Phase 3 trial included deaths up to 105 days after treatment, compared to a previous trial that recorded events up to 30 days. Additionally, he argued it’s “worth noting that most of these events” occurred in elderly patients, with a high portion of them having “advanced, aggressive disease and poorer overall health.”
Based on the data, ADC plans to meet with the FDA in August to discuss next steps. It is preparing for a regulatory submission in the fourth quarter.
Analysts such as Timashev, though, remain unsure of the drug’s future.
In his note, Timashev wrote that while the trial did win on progression-free survival, the “benefits were modest, with no clear overall survival trend, and the significant death imbalance makes the benefit/risk profile difficult to accept and adds considerable regulatory risk.”
Others still remain bullish. Schmidt wrote that “despite the safety hiccup, management expressed confidence in the regulatory path.”
“We believe these data will support conversion from accelerated to full FDA approval,” he added.
