FDA grants accelerated approval to asciminib for newly diagnosed chronic myeloid leukemia

Regulatory approval: On Oct 29, 2024, the FDA granted accelerated approval to asciminib (Scemblix; Novartis) for adults with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Approval was supported by ASC4FIRST (NCT04971226), where major molecular response (MMR) at 48 weeks was higher with asciminib than investigator-selected TKIs (68% vs 49%; difference 19%; p<0.001). Safety and dosing details were included in the FDA communication.

FDA accelerated approval (Oct 29, 2024)

The FDA granted accelerated approval to asciminib (Scemblix; Novartis AG) for adult patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP).

Supporting evidence: ASC4FIRST

Efficacy was evaluated in ASC4FIRST (NCT04971226), a multicenter, randomized, active-controlled, open-label trial (n=405) randomizing 1:1 to asciminib or investigator-selected TKIs (imatinib, nilotinib, dasatinib, or bosutinib).

  • Primary efficacy outcome: MMR rate at 48 weeks
  • MMR at 48 weeks: 68% (95% CI, 61–74) with asciminib vs 49% (95% CI, 42–56) with investigator-selected TKIs; difference 19% (95% CI, 10–28); p<0.001
  • Within the imatinib stratum: 69% (95% CI, 59–78) vs 40% (95% CI, 31–50); difference 30% (95% CI, 17–42); p<0.001

Safety (pooled population)

In pooled safety data from newly diagnosed and previously treated Ph+ CML-CP, common adverse reactions (≥20%) included musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhea. Common lab abnormalities (≥40%) in newly diagnosed Ph+ CML-CP included decreased lymphocytes, leukocytes, platelets, neutrophils, and decreased corrected calcium.

Dosing and regulatory context

Recommended dosage: 80 mg once daily or 40 mg twice daily orally. The FDA review used Project Orbis; reviews at Health Canada and Swissmedic are ongoing. Full prescribing information will be posted on Drugs@FDA.

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