Asciminib Nets Canadian Approval in Newly Diagnosed and Previously Treated Ph+ CML

Asciminib (Scemblix) has received a Notice of Compliance from Health Canada for the treatment of adult patients with Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase (CP-CML) in the newly diagnosed setting or following treatment with at least 1 TKI.¹

The regulatory decision was supported by data from the phase 3 ASC4FIRST trial (NCT04971226), which compared asciminib withan investigator-selected TKI in patients with newly diagnosed CML.² Findings from the study showed that patients who received
asciminib (n = 201) achieved a major molecular response (MMR) rate of 68% (95% CI, 61%-74%) compared with 49% (95% CI, 42%-56%) among patients who received imatinib (Gleevec), nilotinib (Tasigna), dasatinib (Sprycel), or bosutinib (Bosulif; n = 204), translating to a difference of 19% (95% CI, 10%-28%; P < .001).³ The 48-week MMR rates in the asciminib and investigator-selected TKI arms were 66% (95% CI, 56%-75%) and 58% (95% CI, 48%-68%), respectively, representing an estimated difference of 8.17% (95% CI, –5.14% to 21.47%).

“The approval of asciminib represents a significant step forward, expanding treatment options for [patients with] CML,” Dennis Kim, MD, PhD, a clinician investigator in the Princess Margaret Cancer Centre Cancer Clinical Research Unit at Princess Margaret Cancer Centre in Toronto, Canada, stated in a news release.¹ “Having a diverse range of therapies available allows care teams to keep the unique needs of the patient at the center of treatment plans, optimizing outcomes. The ability to prescribe asciminib to newly diagnosed and previously treated patients offers a promising new pathway in our efforts to manage this complex disease effectively and safely.”

In October 2024, the FDA granted accelerated approval to asciminib for the treatment of adult patients with newly diagnosed, Ph-positive CP-CML, based on data from ASC4FIRST.⁴

ASC4FIRST was a multicenter, open-label study that enrolled adult patients with newly diagnosed, previously untreated patients with Ph-positive CML in chronic phase.⁵ Eligible patients were required to be enrolled onto the study within 3 months of diagnosis, have an ECOG performance status of 0 or 1, and have adequate organ function. Patients also needed to have less than 15% of blasts in peripheral blood and bone marrow, less than 30% blasts plus promyelocytes in peripheral blood and bone marrow, less than 20% basophils in the peripheral blood, and a platelet count of at least 100 x 10⁹/L.

Patients were randomly assigned 1:1 to receive oral asciminib at 80 mg once daily or an investigator-selected TKI. In the control arm, patients were treated with daily imatinib at 400 mg, twice daily nilotinib at 300 mg, daily dasatinib at 100 mg, or daily bosotunib at 400 mg.

The primary end point was MMR rate. Secondary end points included 96-week MMR rate, time to discontinuation of study treatment due to adverse effects (AEs), MMR at other scheduled time points, duration of MMR, complete cytogenic response rate, and time to treatment failure.

In terms of safety, the most common any-grade AEs occurring in at least 20% of patients in the investigational arm included musculoskeletal pain (33%), thrombocytopenia (28%), fatigue (25%), upper respiratory tract infections (24%), headache (22%), neutropenia (22%), and diarrhea (20%).³ The most common grade 3 or higher AEs that were reported in at least 5% of patients included thrombocytopenia (17%), neutropenia (14%), increased pancreatic enzymes (9%), and hypertension (9%). Serious AEs were reported in 10% of patients; common serious AEs occurring in at least 1% of patients included pleural effusion (2%), lower respiratory tract infections (1%), thrombocytopenia (1%), pancreatitis (1%), and pyrexia (1%).

“We are proud that Health Canada has expanded its approval of [asciminib], making it a new option for all Canadians with [Ph-positive] CML, whether they are newly diagnosed or have been previously treated,” Mark Vineis, country president, Novartis Canada, added in the news release.¹ “This approval means patients and their physicians now have more choices when deciding on the best course of treatment, offering renewed hope for individuals living with CML, their families, and the health care teams dedicated to their care.”

References

1. Health Canada expands approval of Scemblix, making it an option for newly diagnosed and previously treated chronic myeloid leukemia (CML) patients. News release. Novartis. July 30, 2025. Accessed July 31, 2025. https://www.novartis.com/ca-en/news/media-releases/health-canada-expands-approval-scemblix-making-it-option-newly-diagnosed-and-previously-treated-chronic-myeloid-leukemia-cml-patients
2. Hochhaus A, Wang J, Kim DW, et al. Asciminib in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2024;391(10):885-898. doi:10.1056/NEJMoa2400858
3. Scemblix. Product monograph. July 25, 2025. Accessed July 31, 2025. https://www.novartis.com/ca-en/sites/novartis_ca/files/scemblix_pm_20250725_en.pdf
4. FDA grants accelerated approval to asciminib for newly diagnosed chronic myeloid leukemia. FDA. October 29, 2024. Accessed July 31, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-asciminib-newly-diagnosed-chronic-myeloid-leukemia
5. A study of oral asciminib versus other TKIs in adult patients with newly diagnosed Ph+ CML-CP. ClinicalTrials.gov. Updated July 31, 2025. Accessed July 31, 2025. https://clinicaltrials.gov/study/NCT04971226