FDA Approves Asciminib in Newly Diagnosed Ph+ CML in Chronic Phase

• Accelerated approval has been granted to asciminib (Scemblix) by the FDA for newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase.
• At 48 weeks, the major molecular response (MMR) rate for asciminib was 68% (95% CI, 61%-74%) vs 49% (95% CI, 42%-56%) in patients on standard tyrosine kinase inhibitors (TKIs).
• Asciminib dosing is recommended as either 80 mg once daily or 40 mg twice daily, administered consistently at the same times each day for optimal results.

The FDA has granted asciminib accelerated approval for the treatment of adult patients with newly diagnosed Ph+ CML in chronic phase.¹

Findings from the ASC4FIRST trial (NCT04971226) support this regulatory approval of asciminib in newly diagnosed Ph+ CML in CP. For the primary end point of the study, the MMR rate at 48 weeks, the rate was 68% (95% CI, 61%-74%) in the asciminib arm and 49% (95% CI, 42%-56%) in the investigator-selected TKIs arm, making for a difference of 19% (95% CI, 10%-28%; P <.001). Within the imatinib (Gleevec) stratum, the MMR rate in the asciminib arm was 69% (95% CI, 59%-78%) compared with 40% (95% CI, 31%-50%) in the investigator-selected TKI arm, for a difference of 30% (95% CI, 17%-42%; P <.001).

Microscopic, photorealistic image of chronic myeloid leukemia (CML) cells - Generated with Adobe Firefly

For safety, the most common adverse effects observed in ≥20% 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. The most common laboratory abnormalities seen in ≥40% of patients with newly diagnosed Ph+ CML in chronic phase consisted of 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 of day or 40 mg taken orally twice a day at approximately 12-hour intervals.

About Asciminib and the ASC4FIRST Trial

In 2021, the FDA approved asciminib for patients with Ph+ CML in chronic phase who had been treated with 2 or more TKIs.² Asciminib is among the newest available treatments for patients with CML.

ASC4FIRST is a multicenter, randomized, active-controlled, open-label trial. A total of 405 patients were randomized in a 1:1 fashion and given either asciminib or imatinib, nilotinib (Tasigna), dasatinib (Sprycel), or bosutinib (Bosulif).³ A total of 405 adult patients were enrolled across 111 locations.

In addition to the primary end point of MMR at week 48, the secondary end points included MMR at week 96, time to discontinuation of study treatment due to AEs, 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.

REFERENCES:

1. FDA grants accelerated approval to asciminib for newly diagnosed chronic myeloid leukemia. News release. FDA. October 29, 2024. Accessed October 29, 2024. https://tinyurl.com/4xe45e3n

2. FDA approves Novartis Scemblix® (asciminib), with novel mechanism of action for the treatment of chronic myeloid leukemia. News release. Novartis. October 29, 2021. Accessed October 29, 2024. https://bit.ly/3w5zpq4

3. A study of oral asciminib versus other TKIs in adult patients with newly diagnosed Ph+ CML-CP. ClinicalTrials.gov. Updated May 3, 2024. Accessed October 29, 2024. https://clinicaltrials.gov/study/NCT04971226