Zentalis' shares drop 30% after FDA partially halts WEE1 drug due to sepsis deaths

Zentalis Pharmaceuticals has recently faced a significant setback as the FDA placed three of its clinical trials on partial hold, following two presumed sepsis-related deaths. The trials involved their synthetic lethal WEE1 inhibitor, azenosertib, which was being evaluated as a monotherapy. Specifically, the fatalities occurred in the phase 2 DENALI study, which focused on patients with platinum-resistant ovarian cancer. This hold affects not only the DENALI trial but also a phase 2 study on uterine serous carcinoma and a phase 1 dose-escalation study on solid tumors.

Kimberly Blackwell, M.D., the CEO of Zentalis, emphasized that patient safety remains the company's top priority. She expressed sorrow over the unfortunate deaths and assured that Zentalis is collaborating closely with the FDA to address the clinical hold swiftly. Dr. Blackwell highlighted that over 500 patients have received azenosertib as a monotherapy in various trials, with the DENALI trial alone enrolling over 100 patients in its cohort 1b.

Despite this setback, Zentalis remains optimistic about the future of azenosertib. The company plans to share overall efficacy and safety data from the DENALI cohort 1b later this year. Additionally, Zentalis is on schedule to report topline results from the phase 1 solid tumor trial and a phase 1/2 trial of azenosertib in combination with GSK’s Zejula for ovarian cancer later in 2024.

The news of the trial hold led to a sharp decline in Zentalis' shares, which fell by 30%, dropping from $8.39 to $5.85 in pre-market trading. Nonetheless, the company remains committed to advancing the azenosertib development program and aims to bring this potentially transformative therapy to patients with gynecological cancers.

Last year, Zentalis shared promising data at the ASCO conference from a phase 1b study of azenosertib combined with the chemotherapy drug paclitaxel in ovarian cancer, showing an overall response rate of 50%. These encouraging results prompted preparations for a phase 3 study to compare azenosertib with either carboplatin or paclitaxel in patients with Cyclin E1+ status and platinum-sensitive ovarian cancer. Although the initial plan was to launch this late-stage trial in the first quarter of 2024, the timeline has been pushed back to 2025.

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

In summary, while the FDA's partial hold on azenosertib trials is a significant obstacle for Zentalis Pharmaceuticals, the company remains resolute in its development efforts. With ongoing trials and future plans, Zentalis aims to bring effective treatments to patients battling severe gynecological and other cancers.