FDA Grants Accelerated Approval to Asciminib for Newly Diagnosed Chronic Myeloid Leukemia
Key Insights
The FDA has granted accelerated approval to asciminib (Scemblix) for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (search) (Ph+ CML).
Asciminib, a BCR::ABL1 (search) kinase inhibitor, showed a major molecular response (MMR) rate of 68% at 48 weeks in the ASC4FIRST trial.
The ASC4FIRST trial demonstrated a statistically significant improvement in MMR compared to investigator-selected tyrosine kinase inhibitors (49%).
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to asciminib (Scemblix) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (search) (Ph+ CML) in chronic phase. This decision, announced on October 29, 2024, marks a significant advancement in the therapeutic options available for patients with this form of leukemia.
Asciminib is a first-in-class specific allosteric inhibitor of BCR::ABL1 (search), selectively binding to a myristoyl pocket. This unique mechanism of action induces conformational changes by myristate-binding to the N-terminus of ABL1, offering a novel approach to targeting CML.
Efficacy Demonstrated in ASC4FIRST Trial
The efficacy of asciminib in newly diagnosed Ph-positive CML was evaluated in the ASC4FIRST trial (NCT04971226), a multicenter, randomized, active-controlled, open-label study. The trial randomized 405 patients in a 1:1 ratio to receive either asciminib or investigator-selected tyrosine kinase inhibitors (TKIs), including imatinib, nilotinib, dasatinib, or bosutinib.
The primary efficacy outcome was the major molecular response (MMR) rate at 48 weeks. Results showed a statistically significant improvement in the asciminib arm, with an MMR rate of 68% (95% CI = 61%–74%) compared to 49% (95% CI = 42%–56%) in the investigator-selected TKIs arm (difference = 19%, 95% CI = 10%–28%, P < .001). Notably, within the imatinib stratum, the MMR rate was 69% (95% CI = 59%–78%) in the asciminib arm and 40% (95% CI = 31%–50%) in the investigator-selected TKIs arm (difference = 30%, 95% CI = 17%–42%, P < .001).
Safety Profile
In the pooled safety population of patients with newly diagnosed and previously treated Ph-positive CML, the most common adverse reactions (≥ 20%) were musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhea. The most common laboratory abnormalities (≥ 40%) in patients with newly diagnosed Ph-positive CML were decreased lymphocyte count, decreased leukocyte count, decreased platelet count, decreased neutrophil count, and decreased calcium corrected.
The recommended dosage of asciminib is 80 mg taken orally once daily, at approximately the same time each day, or 40 mg taken orally twice daily, at approximately 12-hour intervals.
Regulatory Context
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, in collaboration with Health Canada and Swissmedic. The application was also granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation, and was approved 1 month ahead of the goal date. The accelerated approval is based on major molecular response rate, and continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s).