FDA puts Curis' leukemia trial on partial hold after patient death spurs review of muscle breakdown

The list of biotechs under clinical hold keeps getting longer. Curis is the latest company to join the list, with the FDA slapping a partial hold on a phase 1/2a leukemia study while it gathers information about the death of a patient.

Massachusetts-based Curis is running the TakeAim Leukemia study to evaluate different doses of IRAK4 kinase inhibitor emavusertib as a monotherapy and in combination with azacitidine or venetoclax. The clinical trial was enrolling patients with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome before the FDA got wind of a safety signal.

The FDA put the study under a partial hold as part of a request for information about the death of an AML patient who experienced rhabdomyolysis and other conditions. Rhabdomyolysis, which describes the breakdown of skeletal muscle, is a known dose-limiting toxicity of emavusertib.

Curis has seen grade 3 rhabdomyolysis cases at the 300-mg, 400-mg and 500-mg doses of emavusertib. With the rate of rhabdomyolysis climbing in line with the dose, Curis chose 300 mg as the recommended phase 2 dose. One of the first 26 patients treated at that dose level developed emavusertib.

The FDA will use the partial hold to assess the patient's death and more broadly to review the data on rhabdomyolysis and Curis’ determination of the recommended phase 2 dose. While the hold is in place, Curis can continue giving doses of 300 mg or lower to patients who are benefiting from emavusertib but cannot enroll any new participants in the study.

"Given the clinical profile of emavusertib observed to date, we are hopeful that the study can be resumed soon, after appropriate review,” Curis CEO James Dentzer said in a statement. Curis will share an update on the timing of talks about a path to market for emavusertib once the impact of the hold on the trial is clearer. 

The partial hold only applies to TakeAim Leukemia. However, Curis has decided to pause enrollment in another phase 1/2 clinical trial, TakeAim Lymphoma, that is studying the drug in patients with B-cell malignancies. Curis will keep enrollment paused pending the resolution of the partial clinical hold.

Investors delivered a swift blow to Curis’ stock price after seeing news of the hold, sending shares down around 30% to below $2 in premarket trading. The fall comes on top of a more than 50% decline over the first three months of the year. Curis ended 2021 with around $140 million, a sum it expects to last it into 2024.