FDA Grants Accelerated Approval to Asciminib for Adult Patients With Newly Diagnosed Ph+ CML-CP

Key Takeaways

Asciminib received FDA accelerated approval for newly diagnosed Ph+ CML-CP based on phase 3 ASC4FIRST trial results.
The trial demonstrated asciminib's superior major molecular response rates at 48 weeks compared to standard TKIs and imatinib.
Experts emphasize the significance of new first-line treatments for improved long-term disease control and reduced side effects.
Asciminib's efficacy, safety, and tolerability may lead to practice-changing implications for CML treatment.

The accelerated approval comes after 48-week major molecular response rate data.

Image credit: MdBabul | stock.adobe.com

Updated October 29, 2024 at 5:00 PM.

The FDA granted an accelerated approval to asciminib (Scemblix; Novartis) for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). The accelerated approval was based on data from the phase 3 clinical trial, ASC4FIRST (NCT04971226), in which asciminib demonstrated stronger major molecular response rate (MMR) data at 48 weeks compared with other investigator-selected (IS) standard of care (SoC) tyrosine kinase inhibitors (TKIs) and imatinib (Gleevec; Novartis) alone.¹

Asciminib is the first CML treatment that works by specifically targeting the ABL myristoyl pocket. It was granted approval in the US to treat newly diagnosed adults and is also approved for previously treated adult patients with Ph+ CML-CP. Additionally, asciminib was granted a breakthrough therapy designation and priority review for the treatment of newly diagnosed patients with Ph+ CML-CP.^1,2

“Many patients who are newly diagnosed with CML struggle to navigate this chronic condition and may switch or even stop treatment because of side effects that interrupt their daily lives,” Lee Greenberger, PhD, chief scientific officer at The Leukemia & Lymphoma Society, said in a news release. “That’s why approvals of new first-line treatment options are so important. For patients, finding a medicine that’s right for them at the very beginning of treatment may lead to better long-term disease control with fewer side effects.”¹

ASC4FIRST (NCT04971226) is an ongoing head-to-head, multicenter, open-label, randomized phase 3 trial studying the efficacy of oral asciminib compared with investigator-selected SoC TKIs—imatinib (Gleevec; Novartis), nilotinib (Tasigna; Novartis), dasatinib (Sprycel; Bristol Myers Squibb), and bosutinib (Bosulif; Pfizer)—in adult patients with newly diagnosed Ph+ CML-CP. A total of 405 patients were randomly assigned to receive 80 mg of oral asciminib once daily, or 400 mg of oral imatinib once daily with food, 300 mg of oral nilotinib twice daily while fasting, 100 mg of oral dasatinib once daily with or without food, or 400 mg of oral bosotunib once daily with food.^1,3

The study’s primary end point is MMR measured at 48 weeks. Secondary end points measured at the time of 96 weeks include MMR and time to discontinuation of study because of adverse events (AEs), and end points assessed at a follow-up period of 5 years include failure-free survival, event-free survival, progression-free survival, and overall survival.³

About The Trial

Trial Name: A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP

ClinicalTrials.gov ID: NCT04971226

Sponsor: Novartis Pharmaceuticals

Completion Date (Estimated): January 2028

According to the 48-week findings, nearly 20% more patients who were treated with asciminib achieved MMR (68%) compared with those treated with a SoC TKI (49%), and about 30% more patients achieved MMR compared with imatinib alone (69% vs 40%; p < .001). In addition, asciminib is also the first treatment for CML that demonstrated superior efficacy as well as a favorable safety and tolerability profile compared with imatinib and other second generation TKIs. Patients treated with asciminib had also achieved deeper rates of MMR including MR4 compared with IS TKIs and imatinib alone (41% vs. 22% and 16%) at week 48.¹

The most common AEs included musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain and diarrhea. Patients treated with asciminib had also reported fewer treatment-related grade 3 or higher AEs (25.5%), dose reductions (6%), and half the rate of AEs that led to treatment discontinuation (4.5%) compared with imatinib alone (33%, 14%, and 11%, respectively) and second generation TKIs (42%, 24%, and 9.8%, respectively). In newly diagnosed patients, the safety profile was consistent with prior studies, and no new safety concerns were observed by the investigators.¹

“While there are a range of effective TKIs currently available for newly diagnosed patients, clinicians frequently have had to weigh sacrificing either efficacy or tolerability,” said Jorge Cortes, MD, director of Georgia Cancer Center. “In the first-of-its-kind ASC4FIRST trial, [asciminib] achieved impressive results across all three parameters of efficacy, safety and tolerability versus all standard of care TKIs. [These asciminib] data [have] the potential to be practice-changing.”¹

REFERENCES

1. Novartis. Novartis Scemblix® FDA approved in newly diagnosed CML, offering superior efficacy, and favorable safety and tolerability profile. News release. October 29, 2024. Accessed October 29, 2024. https://www.novartis.com/news/media-releases/novartis-scemblix-fda-approved-newly-diagnosed-cml-offering-superior-efficacy-and-favorable-safety-and-tolerability-profile

2. Gallagher, A. FDA Grants Priority Review for Asciminib for Chronic Myeloid Leukemia. Pharmacy Times. August 1, 2024. Accessed October 29, 2024. https://www.pharmacytimes.com/view/fda-grants-priority-review-for-asciminib-for-chronic-myeloid-leukemia

3. A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP. ClinicalTrials.gov identifier: NCT04971226. Updated May 3, 2024. Accessed October 29, 2024. https://clinicaltrials.gov/study/NCT04971226