FDA ends partial clinical hold on Zentalis Pharma’s cancer WEE1 inhibitor

The US Food and Drug Administration (FDA) has lifted a partial clinical hold on Zentalis Pharmaceuticals’ experimental cancer drug, azenosertib. This decision enables the company to resume its clinical trials, which were previously halted following safety concerns.

Zentalis Pharmaceuticals experienced a significant increase in its stock value, soaring by 53% from $3.24 at the close of trading on September 13 to $4.96 at the market's opening on September 16. This rise followed the FDA's announcement, which has breathed new life into the company's ambitious plans for azenosertib.

Kimberly Blackwell, the CEO of Zentalis, expressed unwavering belief in the drug's potential. She noted that the company remains confident in azenosertib's therapeutic index and its capacity to address the unmet medical needs of individuals with gynecologic cancers.

The FDA initially imposed the partial hold in June 2024 after two participants in the ovarian cancer study died from presumed blood-related infections linked to the treatment. Azenosertib was under investigation in several trials: a Phase I study targeting solid tumors and two Phase II studies focusing on ovarian and uterine cancers. During the hold, dosing in combination studies continued, but all monotherapy trials were paused.

The recent FDA decision allows Zentalis to resume enrollment across all ongoing azenosertib clinical studies without any modifications to the development plan. This is a significant step forward for the company, which had already shown promising results prior to the hold.

In May 2023, Zentalis had reported positive outcomes from a Phase Ib trial combining azenosertib with chemotherapy in patients with platinum-resistant ovarian cancer. The combination therapy was well tolerated and showed notable clinical activity, achieving a 50% overall response rate when paired with paclitaxel chemotherapy.

Following the FDA's lift of the partial hold, Zentalis has announced its intention to present new monotherapy data for azenosertib. Additionally, the company plans to update stakeholders on the clinical development and data presentation timelines in an event slated for later in 2024.

Azenosertib operates by inhibiting the WEE1 protein, which plays a crucial role in regulating the cell cycle. By blocking WEE1, azenosertib disrupts the cell division process, particularly in cancer cells, preventing proper DNA repair and leading to cell death. This mechanism holds promise for treating various types of cancer, offering a potentially effective therapeutic avenue.

Meanwhile, another biopharmaceutical company, Debiopharm, is also developing a WEE1 inhibitor called Debio-0123. This candidate is currently in a Phase I/II trial in combination with temozolomide for patients with glioblastoma, highlighting the growing interest in WEE1 inhibitors in cancer treatment.

The FDA's decision to lift the hold on azenosertib marks a pivotal moment for Zentalis Pharmaceuticals. As the company resumes its clinical trials, it continues to pursue advancements in cancer therapy, driven by a strong belief in the potential impact of its innovative treatments. The coming months will be crucial as Zentalis aims to further validate the efficacy and safety of azenosertib, striving to bring new hope to patients battling gynecologic and other forms of cancer.