Asciminib Gains FDA Priority Review in Newly Diagnosed CML

Microscopic image of Philadelphia chromosome - Generated with Google Gemini AI

• The FDA has granted priority review to the application of asciminib (Scemblix) for the treatment of newly diagnosed Philadelphia chromosome-positive (Ph+), chronic phase chronic myeloid leukemia (CML).
• The designation is supported by data from the ASC4FIRST study (NCT04971226).
• Asciminib was also approved for patients with Ph+ CML who had been previously treated with 2 or more tyrosine kinase inhibitors (TKIs).

The application of asciminib in newly diagnosed Ph+ CML in chronic phase has been granted priority review by the FDA.¹

FDA priority review designation signals drugs that, if approved, would provide significant improvements to safety or efficacy over available treatments. With priority review, the FDA aims to review and decide on an application within 6 months instead of the standard 10.²

“We welcome the FDA’s decision to grant priority review and breakthrough therapy designations to [asciminib] for newly diagnosed [patients with] CML, which underscores the substantial need for additional effective, safe and tolerable treatment options,” said Rodney Gillespie, senior vice president, therapeutic area head, US Oncology, Novartis, in a press release.¹ "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 2021, the FDA approved asciminib for patients with Ph+ CML in chronic phase who had been treated with 2 or more TKIs.³ Asciminib is among the newest available treatments for patients with CML.

Data Supporting the Application of Asciminib for Newly Diagnosed CML

The application and designation of asciminib for the newly diagnosed indication are supported by findings from the ASC4FIRST study. Data were presented as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and as a plenary at the European Hematology Association (EHA) 2024 Congress.¹

Primary results presented during ASCO with a data cutoff of November 28, 2023, showed that patients with Ph+ chronic phase CML who received asciminib (n = 201) achieved a 48-week major molecular response (MMR) rate of 67.7% (95% CI, 60.7%-74.1%) compared with 49.0% (95% CI, 42.0%-56.1%) among patients who were treated with an investigator-selected TKI (n = 204), representing an 18.9% (95% CI, 9.6%-28.2%; P <.001) improvement.⁴

“A significant number of patients [with CML]—more than half—do not get the deep molecular responses and the type of outcomes that we aim for now that treatment-free remission is becoming increasingly important,” Jorge E. Cortes, MD, the director of the Georgia Cancer Center at Augusta University, said during a presentation of the data. “Asciminib is a TKI with a novel mechanism of action that binds to the myristoyl pocket, raising the possibility of greater selectivity and less toxicity. The drug has been approved for patients who have received multiple prior therapies, and in a randomized trial in that setting [it] showed improved efficacy and safety. [Therefore], we decided to bring it to the frontline setting to see if something similar could be observed.”

About the Phase 3 ASC4FIRST Study

ASC4FIRST is a phase 3, head-to-head, multicenter, open-label, randomized study comparing the oral agent asciminib vs investigator’s choice of first- or second-generation TKIs, including imatinib (Gleevec), nilotinib (Tasigna), dasatinib (Spyrcel), or bosutinib (Bosulif). A total of 405 adult patients were enrolled across 111 locations.¹

The study’s primary end point is MMR at week 48, and secondary end points include MMR at week 96, time to discontinuation of study treatment due to adverse events, complete hematologic response, complete cytogenic response, duration of MMR, time to first MMR, time to treatment failure, failure-free survival, event-free survival, progression-free survival, and overall survival.⁵

REFERENCES:

1. Novartis Scemblix granted FDA priority review for the treatment of adults with newly diagnosed CML. News release. Novartis. July 29, 2024. Accessed July 30, 2024. https://tinyurl.com/4y22rdzz

2. Priority review. FDA. Updated January 4, 2018. Accessed July 30, 2024. https://tinyurl.com/3tsdyar9

3. FDA approves Novartis Scemblix® (asciminib), with novel mechanism of action for the treatment of chronic myeloid leukemia. News release. Novartis. October 29, 2021. Accessed July 30, 2024. https://bit.ly/3w5zpq4

4. 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

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 July 30, 2024. https://clinicaltrials.gov/study/NCT04971226