'Rapid' path for Curis' lead leukemia drug hits roadblock with partial clinical hold after patient death
A patient has died in a Phase I/IIa trial of Curis’ lead drug after experiencing rhabdomyolysis, “among several conditions.” As a result, FDA has slapped a partial clinical hold on the study.
The hold could throw the biotech’s plans for a potential “rapid regulatory path” of the drug into question. Just six weeks ago, Curis said it expected to meet with the FDA to discuss the registrational route for emavusertib as a monotherapy in the first half of this year.
But the agency wants more data from the open-label study, which is testing emavusertib, also known as CA-4948, in patients with relapsed or refractory acute myeloid leukemia, or high-risk myelodysplastic syndrome. The oral small molecule is being tested alone and in combination with azacitidine or venetoclax. Emavusertib is an inhibitor of Interleukin-1 receptor-associated kinase 4.
The news sent Curis’ stock $CRIS sliding nearly 30% before the opening bell Monday.
The FDA wants more information on the death of the patient, who had R/R AML. The patient had rhabdomyolysis, “which has previously been identified as a dose-limiting toxicity of emavusertib,” Curis said in its Monday morning statement. Proteins and electrolytes from damaged muscle tissue are released into the blood in rhabdomyolysis, which can lead to heart and kidney damage that results in permanent disability or death. The regulator also wants safety, efficacy and other data, including Curis’ determination of the recommended Phase II dose.
With the partial hold, the TakeAim Leukemia study cannot enroll new patients. Existing study patients are allowed to continue treatment at doses of 300mg BID or lower. Curis was planning to study the oral drug up to 400mg BID, according to the trial listing. ClinicalTrials.gov estimates that 178 patients have been enrolled.
“Given the clinical profile of emavusertib observed to date, we are hopeful that the study can be resumed soon, after appropriate review. We continue to be confident in the potential of emavusertib to address the high unmet need of patients with AML or MDS,” CEO James Dentzer said in the news release. Curis is committed to patient safety, he added.
Patients and investors will have to wait for more details about when Curis will discuss emavusertib’s registrational path with the FDA.
The company is also pausing enrollment in its Phase I/II study of emavusertib in patients with B-cell malignancies. The partial hold doesn’t apply to that trial, but Curis decided to take the action as it awaits resolution of the hold.
Curis gained rights to emavusertib in exchange for nearly 20% of its outstanding common stock to Aurigene in January 2015. Curis is also on tap to dole out up to $52.5 million in milestone payments for the AML program.