Asciminib Receives FDA Priority Review for Newly Diagnosed Ph+ CP-CML

The FDA has granted priority review to asciminib (Scemblix) for the treatment of patients with newly diagnosed Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase (CP-CML).¹

The regulatory decision was supported by findings from the phase 3 ASC4FIRST study (NCT04971226), in which patients with Ph-positive CP-CML experienced superior major molecular response (MMR) rates with asciminib compared with the standard-of-care (SOC) TKIs nilotinib (Tasigna), imatinib (Gleevec), bosutinib (Bosulif), and dasatinib (Sprycel). Asciminib is the first treatment to demonstrate an efficacy advantage over SOC TKIs alongside a favorable safety and tolerability profile in CML.¹

Data presented at the 2024 ASCO Annual Meeting showed that, at a data cutoff of November 28, 2023, the 48-week MMR rate was 67.7% among patients who received asciminib (n = 201) vs 49.0% among patients treated with an investigator-selected TKI (n = 204), translating to a difference of 18.9% (95% CI, 9.6%-28.2%; P < .001). Notably, in the imatinib stratum of the investigational arm (n = 101) and comparator arm (n = 102), the 48-week MMR rates were 69.3% vs 40.2%, respectively, for a difference of 29.6% (95% CI, 16.9%-42.2%; P < .001).²

Findings from this trial were also presented at the 2024 EHA Congress and published in The New England Journal of Medicine.¹

“We welcome the FDA’s decision to grant priority review and breakthrough therapy designations to asciminib for patients with newly diagnosed CML, which underscores the substantial need for additional effective, safe, and tolerable treatment options,” Rodney Gillespie, senior vice president and therapeutic area head of US Oncology at Novartis, stated in a news release. "The ASC4FIRST data indicate that asciminib, if approved, has the potential to address a critical gap in CML by offering a highly effective treatment along with a favorable safety and tolerability profile.”

In May 2024, asciminib was granted FDA breakthrough therapy designation for the treatment of adult patients with newly diagnosed Ph-positive CP-CML.³ The agent is currently under evaluation by the regulatory agency’s Real-Time Oncology Review program.¹

The agent also received priority review and breakthrough therapy designations at the time of the original new drug application for the treatment of adult patients with Ph-positive CP-CML with prior exposure to 2 or more TKIs. In October 2021,the FDA granted accelerated approval to asciminibfor this indication and concurrently approved asciminib for adult patients with Ph+ CP-CML harboring a BCR::ABL1T315I mutation.⁴ The agent is also approved by the European Medicines Agency and several other regulatory agencies for this patient population.¹

ASC4FIRST Trial

The multicenter, open-label study enrolled 405 adult patients with newly diagnosed Ph-positive CP-CML who were TKI naive. Patients were stratified according to prerandomization TKI selection (imatinib vs second-generation TKI) and European Treatment and Outcome Study long-term survival risk category (low vs intermediate vs high).⁵

Eligible patients were randomly assigned 1:1 to receive either 80 mg of asciminib daily or investigator’s choice of TKI. Within the investigator-selected TKI arm, patients were further divided to receive either a second-generation TKI or imatinib; the investigational arm included both imatinib and second-generation TKI strata.

The primary end point was the 48-week MMR rate. MMR rate at 96 weeks, time to discontinuation due to adverse effects (AEs), MMR at scheduled data collection time points, complete hematological response rate, duration of MMR, event-free survival, progression-free survival, and overall survival were key secondary end points.

Additional findings from ASC4FIRST showed that more deep molecular responses were achieved by patients treated with asciminib compared with those who received an investigator-selected TKIs. The MR4 rates at week 48 were 38.8% vs 20.6%, respectively, and the 48-week MR4.5 rates were 16.9% vs 8.8%, respectively.²

Patients who received asciminib vs imatinib and second-generation TKIs experienced fewer grade 3 or higher AEs (38% vs 44% and 55%), dose adjustments (30% vs 39% and 53%), and AEs leading to treatment discontinuation (5% vs 11% and 10%). The safety profile of asciminib was consistent with data from prior registration studies, and no new safety signals were reported. The study is ongoing.^1,2

References

1. Novartis Scemblix granted FDA priority review for the treatment of adults with newly diagnosed CML. News release. Novartis. July 30, 2024. Accessed July 30, 2024. https://www.novartis.com/news/media-releases/novartis-scemblix-granted-fda-priority-review-treatment-adults-newly-diagnosed-cml
2. Hughes TP, Hochhaus A, Takahashi N, et al. ASC4FIRST, a pivotal phase 3 study of asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed patients (pts) with chronic myeloid leukemia (CML): primary results. J Clin Oncol. 2024;42(suppl 17):LBA6500. doi:10.1200/JCO.2024.42.17_suppl.LBA6500
3. Novartis receives FDA breakthrough therapy designation for Scemblix in 1L CML. News Release. Novartis. May 10, 2024. Accessed July 30, 2024. https://www.novartis.com/news/novartis-receives-fda-breakthrough-therapy-designation-scemblix-1l-cml
4. Asciminib. Prescribing information. Novartis; 2024. Accessed July 30, 2024. https://www.novartis.com/us-en/sites/novartis_us/files/scemblix.pdf
5. A study of oral asciminib versus other TKIs in adult patients with newly diagnosed Ph+ CML-CP. ClinicalTrials.gov. Updated May 3, 2024. Accessed May 29, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04971226