FDA sparks hope for Curis, lets biotech resume enrollment for part of phase 1/2 leukemia study

Curis has received another spark of hope as the FDA lets the biotech resume enrollment for a part of its phase 1/2 study assessing emavusertib in patients with leukemia.

In April 2022, the FDA placed a partial clinical hold on the study—dubbed TakeAim Leukemia and examining emavusertib in patients with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome—after a patient death spurred a review. A week later, the agency slapped a separate partial hold on the biotech’s TakeAim Lymphoma study examining the same drug but in patients with relapsed or refractory B-cell malignancies.

The partial holds came so the FDA could investigate the safety and efficacy of emavusertib—an IRAK4 kinase inhibitor—following an information request about the death of an AML patient who experienced rhabdomyolysis and other conditions. Rhabdomyolysis—the breakdown of skeletal muscle—is a known dose-limiting toxicity of emavusertib.

Curis received some good news Aug. 18 when the FDA lifted the partial hold on its lymphoma trial. Curis and the FDA agreed on a strategy for rhabdomyolysis identification and management as well as on the enrollment of at least nine more patients at the 200-mg dose level of emavusertib in combination with Imbruvica.  

Now, the FDA is letting Curis resume patient enrollment in the phase 1a portion of TakeAim Leukemia, according to an Aug. 30 release. The biotech intends to enroll at least nine more patients at the 200-mg dose level of emavusertib, which has an FDA orphan-drug tag in AML.

Before lifting the enrollment restriction, the FDA reviewed additional data from Curis about the risk of rhabdomyolysis along with the company's strategy for using lab measurements to identify the condition and manage it if detected. 

The partial hold remains in place for the combination therapy phase (phase 1b) of TakeAim Leukemia, in which Curis was evaluating doses of emavusertib with azacitidine or the AbbVie-Genentech drug Venclexta. The trial’s expansion phase (phase 2a) is also still under a partial hold. Both holds will remain in place until phase 1a is completed and the FDA greenlights the next phases.

"We are pleased to announce the results of the FDA's review and to have addressed potential concerns about the identification and management of rhabdomyolysis," said James Dentzer, president and CEO of Curis. "We are working with our clinical sites to quickly resume enrollment of additional patients."