The FDA put three clinical studies of Zentalis’ WEE1 inhibitor on partial hold following two patient deaths likely from sepsis in one study earlier this year.
The two patients were part of the Phase 2 DENALI study, which was testing azenosertib in patients with ovarian cancer that has developed a resistance to platinum-based chemotherapy.
The partial hold extends to two other trials studying azenosertib alone: the Phase 2 TETON study in an aggressive form of endometrial cancer called uterine serous carcinoma, and a Phase 1 study in solid tumors.
The partial hold means that patients already in the trials can continue to receive treatment, but new patient enrollment has been paused.
The company’s shares $ZNTL fell 30% Tuesday morning.
Kim BlackwellIn a statement, Zentalis CEO Kim Blackwell noted that “over 500 patients have been treated with azenosertib monotherapy to date.” Including combination studies, almost 800 patients have received the drug, according to Zentalis.
Overall, eight deaths have been reported in studies that tested azenosertib alone and with other treatments, according to a Zentalis presentation on Tuesday morning. Seven of the eight cases were due to blood toxicities, which TD Cowen analyst Tyler Van Buren noted is “a well-known and understood on-target toxicity of WEE1 inhibition.”
WEE1 is a DNA repair enzyme that’s highly expressed in some cancers. AstraZeneca had been developing a WEE1 inhibitor called adavosertib before it cut the program in 2022.
“The partial clinical hold this late in development seems odd given that it is a well-understood, on-target toxicity and [azenosertib] has treated ~800 patients over the past ~5 years, and [adavosertib] has treated another few hundred,” Van Buren wrote.
Van Buren said the hold “should be resolved quickly.”
Zentalis plans to share topline results from a cohort of patients in the DENALI study and two other studies of azenosertib in the second half of the year.