VJToday

FDA grants accelerated approval to asciminib for adult patients with newly diagnosed Ph+ CML in chronic phase

On October 29, 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to asciminib for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP).1

Asciminib is a novel tyrosine kinase inhibitor (TKI) that uniquely targets the ABL myristoyl pocket and has increased selectivity and potent activity against BCR-ABL1. This novel mechanism helps overcome resistance associated with other TKIs and offers an alternative for patients with limited treatment options.2 

The approval of asciminib is supported by data from the open-label, multi-center, randomized Phase III ASC4FIRST trial (NCT04971226), which compared the efficacy of asciminib versus investigator-selected TKIs (imatinib, nilotinib, dasatinib, and bosutinib) in 405 patients with newly diagnosed Ph+ CML in CP. In this trial, patients were randomized 1:1 to receive either asciminib or an investigator-selected TKI. The primary endpoint was major molecular response (MMR) rate at 48 weeks.1

The MMR rate at 48 weeks was 68% (95% CI: 61, 74) in the asciminib arm compared with 49% (95% CI: 42, 56) in the investigator-selected TKI arm (p < 0.001), reflecting a significant difference of 19% (95% CI: 10, 28). Asciminib demonstrated even higher efficacy among patients who were assigned to receive imatinib in the trial. The MMR rate was 69% (95% CI: 59, 78) for asciminib versus 40% (95% CI: 31, 50) for imatinib (p < 0.001). These results highlight asciminib’s potential as a more effective first-line therapy for achieving molecular responses in Ph+ CML.1

We recently caught up with Jorge Cortes, MD, Georgia Cancer Center, Augusta University, Augusta, GA, who shared updates from the ASC4FIRST trial. Dr Cortes stated, “There was a very significant difference in the rate of major molecular response by 48 weeks, which was the point where the primary endpoint was measured, in favor of [asciminib] both against imatinib, a delta of almost 30%, and versus all of the TKIs, a delta of almost 20%.”

The safety profile for asciminib was generally consistent with findings in previously treated CML populations. Common adverse events (≥20%) included musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhea. Laboratory abnormalities observed in ≥40% of patients included decreased counts of lymphocytes, leukocytes, platelets, neutrophils, and decreased corrected calcium.1

The approval of asciminib offers a new and effective first-line option for adult patients with newly diagnosed Ph+ CML in CP, with improved molecular response outcomes and a manageable safety profile.

References

  1. U.S. Food and Drug Administration. FDA grants accelerated approval to asciminib for newly diagnosed chronic myeloid leukemia. Available here. (Last accessed 30/10/2024).
  2. Padala S, Cortes J. Asciminib in chronic myeloid leukemia: a STAMP for expedited delivery? Haematologica. 2023 Nov 1;108(11):2913-2918.

Written by Anya Dragojlovic Kerkache