FDA Approves Asciminib for Newly Diagnosed Philadelphia Chromosome-Positive CML

Key Insights

• The FDA granted accelerated approval to asciminib for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase.
• Asciminib demonstrated a major molecular response (MMR) rate of 68% at 48 weeks, compared to 49% in patients treated with standard tyrosine kinase inhibitors (TKIs).
• The recommended dosage for asciminib is either 80 mg once daily or 40 mg twice daily, consistently administered at the same times each day.

The FDA has granted accelerated approval to asciminib (Scemblix) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. This decision is based on the ASC4FIRST trial, which demonstrated a statistically significant improvement in major molecular response (MMR) rates compared to standard tyrosine kinase inhibitors (TKIs).

ASC4FIRST Trial Results

The ASC4FIRST trial (NCT04971226) compared asciminib to investigator-selected TKIs in newly diagnosed Ph+ CML patients in chronic phase. At 48 weeks, the MMR rate in the asciminib arm was 68% (95% CI, 61%-74%) compared to 49% (95% CI, 42%-56%) in the TKI arm, representing a 19% difference (95% CI, 10%-28%; P < .001). Notably, within the imatinib (Gleevec) stratum, asciminib achieved a 69% MMR rate (95% CI, 59%-78%) versus 40% (95% CI, 31%-50%) for investigator-selected TKIs (P < .001), a difference of 30%.

Safety Profile

The most common adverse effects (≥20%) observed in patients with newly diagnosed and previously treated Ph+ CML in chronic phase included musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhea. Common laboratory abnormalities (≥40%) included decreased lymphocyte, leukocyte, platelet, and neutrophil counts, as well as decreased corrected calcium.

Dosage and Administration

The recommended dosage of asciminib is 80 mg orally once daily, administered at the same time each day, or 40 mg orally twice daily, taken approximately 12 hours apart.

Asciminib Background

Asciminib was previously approved in 2021 for Ph+ CML patients in chronic phase who had received two or more prior TKIs. The ASC4FIRST trial was a multicenter, randomized, active-controlled, open-label study involving 405 patients randomized 1:1 to either asciminib or investigator-selected TKIs (imatinib, nilotinib (Tasigna), dasatinib (Sprycel), or bosutinib (Bosulif)). Secondary endpoints included MMR at week 96, time to treatment discontinuation due to adverse events, complete hematologic response, complete cytogenetic response, duration of MMR, time to first MMR, time to treatment failure, failure-free survival, event-free survival, progression-free survival, and overall survival.