The US Food and Drug Administration (FDA) has lifted a partial clinical hold on Zentalis Pharmaceuticals’ azenosertib, allowing the company to continue evaluating the drug as a treatment for cancer.
Following the FDA decision, Zentalis’ stock was up by 53%, from $3.24 at closing on 13 September to $4.96 at the market opening on 16 September.
In an announcement, Zentalis’s CEO Kimberly Blackwell said: “Our confidence in the therapeutic index of azenosertib has been unwavering, and we continue to believe in the potential for this treatment to address unmet medical needs faced by people living with gynecologic malignancies.”
The FDA placed the partial hold on three studies investigating azenosertib in June 2024 following the death of two trial participants. Azenosertib was being investigated in solid tumours in a Phase I study (NCT04158336) and more specifically in patients with ovarian (NCT05128825) and uterine cancer (NCT04814108) in two Phase II studies. Two patients in the ovarian cancer study died due to presumed blood-related infection associated with the treatment.
Dosing for participants already enrolled in combination studies investigating azenosertib continued, but all trials investigating the candidate as a monotherapy were halted. The FDA has now cleared the company to resume enrolment in all ongoing azenosertib clinical studies with no changes in the clinical development plan.
In May 2023, prior to the clinical hold, Zentalis shared positive data from a Phase Ib trial (NCT04516447) of azenosertib combined with chemotherapy in patients with platinum-resistant ovarian cancer. Azenosertib was well tolerated in combination with multiple chemotherapy types and demonstrated significant clinical activity. The highest overall response rate (ORR) was 50% with azenosertib plus paclitaxel chemotherapy.
In the 16 September announcement, Zentalis said it plans to present azenosertib monotherapy data and provide additional updates to the azenosertib clinical development and other data presentation timelines at a corporate event later in 2024.
Azenosertib blocks the WEE1 protein, which regulates the cell cycle by pausing cell division to allow DNA repair when damage occurs. This disruption of the cell cycle – especially in cancer cells – can prevent proper DNA repair and lead to the cell death.
Switzerland-based biopharma Debiopharm also has a WEE1 inhibitor in development, dubbed Debio-0123. The candidate is currently being investigated in a Phase I/II trial (NCT05765812) combined with temozolomide to treat patients with glioblastoma.
