The FDA has approved asciminib, a STAMP inhibitor that binds to the ABL myristoyl pocket, for the  treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase, according to a press release.

The FDA granted accelerated approval to asciminib for patients treated with two or more tyrosine kinase inhibitors and full approval for those with CML with a T315I mutation. 

The FDA based the approval on findings from the phase 3 randomized, open label ASCEMBL trial, which included 233 patients with CML treated with two or more TKIs who were randomized 2:1 to either 40 mg asciminib twice daily or 500 mg of bosutinib once daily. 

The primary efficacy outcome of the ASCEMBL trial was major molecular response (MMR) at 24 weeks, with an MMR rate of 25% (95% CI, 13-33) in the asciminib arm compared to 13% (95% CI, 6.5-23; P = 0.029) in the bosutinib group. Median MMR had not been reached with a median follow-up of 20 months. 

The FDA also evaluated data from the CABL001X2101 trial, which included patients with Philadelphia chromosome-positive CML with the T315I mutation. Overall, 45 patients treated with asciminib 200 mg twice daily were evaluable for efficacy. Researchers reported MMR rates of 42% (95% CI, 28-58) at 24 weeks and 49% (95% CI, 34-64) at 96 weeks.

“CML can be difficult to treat when currently available treatments fail patients, when treatment side effects cannot be tolerated, or sometimes both,” Michael J. Mauro, MD, of the Memorial Sloan Kettering Cancer Center, said in the manufacturer’s release. “The addition of [asciminib] into the CML treatment landscape gives us a novel approach to combat this blood cancer, helping address clinical challenges in patients struggling after switching to a second treatment, as well as in patients who develop the T315I mutation and face significantly worse outcomes.” 

The most common adverse reactions among patients treated with asciminib included upper respiratory tract infections and musculoskeletal pain. The most common laboratory abnormalities included decreased platelet counts, increased triglycerides, and decreased neutrophil counts, and hemoglobin. 

Prior to approval, the FDA granted the asciminib application priority review, breakthrough designations, fast track designation, and orphan drug designation.