Zentalis' shares plunge 30% after FDA places WEE1 drug on partial hold over sepsis deaths

The FDA has placed three trials of Zentalis’ WEE1 candidate on partial hold in the wake of two deaths that are presumed to be from sepsis.

The fatalities occurred in the phase 2 DENALI study, which was evaluating the synthetic lethal WEE1 inhibitor azenosertib in patients with platinum-resistant ovarian cancer. The hold also extends to the other studies of azenosertib as a monotherapy—a phase 2 trial in uterine serous carcinoma and a phase 1 dose-escalation study in solid tumors.

“Patient safety is our top priority and any deaths that occur in the setting of clinical trials are unfortunate,” Zentalis CEO Kimberly Blackwell, M.D., said in the June 18 release. “We are working closely with the FDA to resolve this partial clinical hold as quickly as possible.”

Over 500 patients have been treated with azenosertib as a monotherapy across various trials to date, Blackwell pointed out, with the DENALI trial alone enrolling over 100 patients in cohort 1b.

“We look forward to sharing these results along with overall efficacy and safety data from DENALI cohort 1b later this year,” the CEO added.

Azenosertib is Zentalis’ only clinical-stage asset. The biotech’s shares plummeted 30% in the wake of the news, dropping to $5.85 in pre-market trading on Tuesday morning from a Monday closing price of $8.39.

The company is still on track to report topline results from the phase 1 solid tumor trial as well as a phase 1/2 trial of azenosertib in combination with GSK’s Zejula for ovarian cancer later in 2024, according to the release.

“Zentalis remains committed to the azenosertib development program and bringing this potentially practice-changing therapy to patients with gynecological malignancies,” the biotech said in the release.

The company previously shared data at last year’s ASCO conference from a phase 1b study of azenosertib plus the chemotherapy paclitaxel in ovarian cancer that demonstrated an overall response rate of 50%. The biotech said at the time that the data were enough to begin preparations for a phase 3 study comparing azenosertib with either carboplatin or paclitaxel in patients with Cyclin E1+status and with platinum-sensitive ovarian cancer.

The original plan was to launch a late-stage trial off the back off the data in the first quarter of 2024, although this timeline has since been pushed back to 2025.

Zentalis returned to ASCO earlier this month armed with data from a phase 1 trial of azenosertib in combination with the chemotherapy gemcitabine in relapsed or refractory osteosarcoma. At the maximum tolerated dose, the most common adverse events of grade 3 or above were thrombocytopenia and lymphopenia, although the company pointed out that there were no grade 4 thrombocytopenia events or instances of febrile neutropenia at this dose.