Asciminib Recieves FDA Precedence Evaluate for Newly Identified Ph+ CP-CML

The FDA has granted precedence evaluate to asciminib (Scemblix) for the therapy of sufferers with newly recognized Philadelphia chromosome (Ph)–constructive continual myeloid leukemia (CML) in continual part (CP-CML).¹

The regulatory choice was supported by findings from the part 3 ASC4FIRST examine (NCT04971226), wherein sufferers with Ph-positive CP-CML skilled superior main molecular response (MMR) charges with asciminib in contrast with the standard-of-care (SOC) TKIs nilotinib (Tasigna), imatinib (Gleevec), bosutinib (Bosulif), and dasatinib (Sprycel). Asciminib is the primary therapy to display an efficacy benefit over SOC TKIs alongside a positive security and tolerability profile in CML.¹

Information offered on the 2024 ASCO Annual Assembly confirmed that, at a knowledge cutoff of November 28, 2023, the 48-week MMR price was 67.7% amongst sufferers who obtained asciminib (n = 201) vs 49.0% amongst sufferers handled with an investigator-selected TKI (n = 204), translating to a distinction of 18.9% (95% CI, 9.6%-28.2%; P < .001). Notably, within the imatinib stratum of the investigational arm (n = 101) and comparator arm (n = 102), the 48-week MMR charges have been 69.3% vs 40.2%, respectively, for a distinction of 29.6% (95% CI, 16.9%-42.2%; P < .001).²

Findings from this trial have been additionally offered on the 2024 EHA Congress and printed in The New England Journal of Drugs.¹

“We welcome the FDA’s choice to grant precedence evaluate and breakthrough remedy designations to asciminib for sufferers with newly recognized CML, which underscores the substantial want for extra efficient, secure, and tolerable therapy choices,” Rodney Gillespie, senior vice chairman and therapeutic space head of US Oncology at Novartis, acknowledged in a information launch. “The ASC4FIRST knowledge point out that asciminib, if authorized, has the potential to handle a vital hole in CML by providing a extremely efficient therapy together with a positive security and tolerability profile.”

In Could 2024, asciminib was granted FDA breakthrough remedy designation for the therapy of grownup sufferers with newly recognized Ph-positive CP-CML.³ The agent is presently underneath analysis by the regulatory company’s Actual-Time Oncology Evaluate program.¹

The agent additionally obtained precedence evaluate and breakthrough remedy designations on the time of the unique new drug utility for the therapy of grownup sufferers with Ph-positive CP-CML with prior publicity to 2 or extra TKIs. In October 2021,the FDA granted accelerated approval to asciminibfor this indication and concurrently authorized asciminib for grownup sufferers with Ph+ CP-CML harboring a BCR::ABL1T315I mutation.⁴ The agent can also be authorized by the European Medicines Company and several other different regulatory companies for this affected person inhabitants.¹

ASC4FIRST Trial

The multicenter, open-label examine enrolled 405 grownup sufferers with newly recognized Ph-positive CP-CML who have been TKI naive. Sufferers have been stratified in response to prerandomization TKI choice (imatinib vs second-generation TKI) and European Remedy and Consequence Examine long-term survival danger class (low vs intermediate vs excessive).⁵

Eligible sufferers have been randomly assigned 1:1 to obtain both 80 mg of asciminib each day or investigator’s selection of TKI. Inside the investigator-selected TKI arm, sufferers have been additional divided to obtain both a second-generation TKI or imatinib; the investigational arm included each imatinib and second-generation TKI strata.

The first finish level was the 48-week MMR price. MMR price at 96 weeks, time to discontinuation attributable to hostile results (AEs), MMR at scheduled knowledge assortment time factors, full hematological response price, length of MMR, event-free survival, progression-free survival, and general survival have been key secondary finish factors.

Extra findings from ASC4FIRST confirmed that extra deep molecular responses have been achieved by sufferers handled with asciminib in contrast with those that obtained an investigator-selected TKIs. The MR4 charges at week 48 have been 38.8% vs 20.6%, respectively, and the 48-week MR4.5 charges have been 16.9% vs 8.8%, respectively.²

Sufferers who obtained asciminib vs imatinib and second-generation TKIs skilled fewer grade 3 or increased AEs (38% vs 44% and 55%), dose changes (30% vs 39% and 53%), and AEs resulting in therapy discontinuation (5% vs 11% and 10%). The protection profile of asciminib was in line with knowledge from prior registration research, and no new security indicators have been reported. The examine is ongoing.^1,2

References

1. Novartis Scemblix granted FDA precedence evaluate for the therapy of adults with newly recognized CML. Information launch. Novartis. July 30, 2024. Accessed July 30, 2024. https://www.novartis.com/information/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 part 3 examine of asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly recognized sufferers (pts) with continual myeloid leukemia (CML): major outcomes. J Clin Oncol. 2024;42(suppl 17):LBA6500. doi:10.1200/JCO.2024.42.17_suppl.LBA6500
3. Novartis receives FDA breakthrough remedy designation for Scemblix in 1L CML. Information Launch. Novartis. Could 10, 2024. Accessed July 30, 2024. https://www.novartis.com/information/novartis-receives-fda-breakthrough-therapy-designation-scemblix-1l-cml
4. Asciminib. Prescribing data. Novartis; 2024. Accessed July 30, 2024. https://www.novartis.com/us-en/websites/novartis_us/information/scemblix.pdf
5. A examine of oral asciminib versus different TKIs in grownup sufferers with newly recognized Ph+ CML-CP. ClinicalTrials.gov. Up to date Could 3, 2024. Accessed Could 29, 2024. https://traditional.clinicaltrials.gov/ct2/present/NCT04971226