Two approval for asciminib were issued by the FDA for the treatment of CML with a Ph+ CML-CP mutation.
The FDA has approved granted both an accelerated approval for asciminib (Scemblix) for the treatment of chronic myeloid leukemia (CML) for both adult patients with Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine kinase inhibitors (TKIs), and full approval for adult patients with Ph+ CML-CP with the T315I mutation, according to a press release by Novartis.1
“CML can be difficult to treat when currently available treatments fail patients, when treatment side effects cannot be tolerated, or sometimes both,” said Michael J. Mauro, MD, hematologist and Myeloproliferative Neoplasms Program Leader at Memorial Sloan Kettering Cancer Center, in a press release. “The addition of Scemblix 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 approval is based on data from the phase 3 ASCEMBL trial of asciminib versus bosutinib (Bosulif) on patients with Philadelphia chromosome-positive (Ph+) CML in chronic phase who were previously treated with 2 or more tyrosine kinase inhibitors (TKIs). Data from a phase 1 study of asciminib in patients with Ph+ CML in chronic phase who harbor a T315I mutation also support the NDA.
In ASCEMBL (NCT03106779), the primary end point of improvement in major molecular response (MMR) at 24 weeks was achieved in 2020. The MMR rate observed in the 157 patients treated with asciminib 40 mg twice daily was 25.5% compared with only 13.2% in the 76 patients treated with bosutinib 500 mg once daily, reaching a 12.2% difference between the 2 arms (95% CI, 2.19-22.3; 2-sided P = .029). Of those who had a response, the median time to MMR was 12.7 weeks with asciminib versus 14.3 weeks with bosutinib.2
Deep molecular responses were also observed in the patients and appeared to be better for patients treated with asciminib than those treated with bosutinib. In the asciminib versus the bosutinib arm, deep molecular responses were seen in 5.3% and 1.3%, respectively. The complete cytogenetic response rate at 24 weeks was 40.8% in the asciminib arm compared with 24.2% with the control therapy. Asciminib also appeared to improve MMR across the multiple subgroups assessed in the study.
All patients were assessed from safety. In these patients any-grade adverse events (AEs) were observed in 89.7% of the asciminib versus 96.1% of the bosutinib arm, and any-grade treatment-related AEs occurred in 63.5% and 88.2%, respectively. Serious AEs leading to fatality were observed in 1.3% of the experimental arm and 1.3% of the control arm. Nine AEs led to discontinuation of treatment with asciminib and 16 lead patients to discontinue bosutinib. Dose adjustment and or interruption occurred in 37.8% of the asciminib arm versus 60.5% of the bosutinib arm. Notably, 66.0% of patients treated with asciminib in the study required additional therapy compared with 88.2% of those treated with bosutinib. Also, 2 patients in the asciminib died due to ischemic stroke and arterial embolism, and 1 patient in the bosutinib arm died of septic shock.
The most frequently seen ≥3 AEs in the asciminib versus the bosutinib arm respectively were thrombocytopenia (17.3% vs 6.6%), neutropenia (14.7% vs 11.8%), diarrhea (0%, vs10.5%), and increased alanine aminotransferase (0.6% vs 14.5%).
“The introduction of TKIs twenty years ago revolutionized treatment for CML; however, there remain many patients who do not respond adequately to at least two available treatments and often experience challenging side effects that add a burden to their daily lives,” said Lee Greenberger, chief scientific officer at The Leukemia & Lymphoma Society in a press release. “The approval of Scemblix may offer hope to patients by addressing gaps in CML care.”