FDA Grants Priority Review to Novartis’ Scemblix for Newly Diagnosed Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase

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The FDA has granted priority to review to Novartis’ Scemblix (asciminib) for newly diagnosed adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase (Ph+ CML-CP). According to the company, the designation was based on promising results from the Phase III ASC4FIRST trial, in which Scemblix showed superior major molecular response (MMR) rates compared to current standard-of-care (SoC) tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, and bosutinib.¹

“We welcome the FDA’s decision to grant Priority Review and Breakthrough Therapy designations to Scemblix for newly diagnosed CML patients, which underscores the substantial need for additional effective, safe and tolerable treatment options,” said Rodney Gillespie, SVP, therapeutic area head, US oncology, Novartis, in a press release. "The ASC4FIRST data indicate that Scemblix, 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.”

The head-to-head, multi-center, open-label, randomized ASC4FIRST study compared oral Scemblix 80 mg QD vs. investigator-selected first- or second-generation TKIs in 405 adult patients with newly diagnosed Ph+ CML-CP. The study had two primary endpoints, which were to compare the efficacy of asciminib with investigator-selected SoC TKIs and to compare the efficacy with that of TKI within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients who achieve MMR at week 48.

Scemblix was found to achieve response rates of 68% compared with 49% with selected TKIs and 40% with imatinib monotherapy. Further, Novartis stated that Scemblix is the first CML treatment to show superior efficacy along with a favorable safety and tolerability profile vs. imatinib and second generation TKIs, with fewer grade ≥3 adverse events (AEs) (38% vs. 44% and 55%, respectively), dose adjustments (30% vs. 39% and 53%, respectively) and half the rate of AEs leading to treatment discontinuation (5% vs. 11% and 10%, respectively).

The study is currently in progress, with key secondary endpoints currently being evaluated, including proportion of patients who achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE by week 96 currently being evaluated. Additional secondary safety endpoints include MMR, MR4, MR4.5, complete hematological response and BCR:ABL1 ≤1% at and by all scheduled data collection time points; duration of and time to first MMR, MR4, and MR4.5; time to treatment failure; event-free survival, failure-free survival, progression-free survival, and overall survival.

The safety profile of Scemblix was consistent with previous studies, and no new safety signals have been reported. Common AEs included nose, throat, or sinus infections; muscle, bone, or joint pain; rash; tiredness; nausea; and diarrhea. Additionally, blood test abnormalities include decreased blood counts of platelets, white blood cells, and red blood cells, and increased blood levels of triglycerides, creatine kinase, liver enzymes, or pancreas enzymes.¹

According to the American Cancer Society, every one in 526 people will be diagnosed with CML in the United States during their lifetime. By the end of this year, it is estimated that approximately 9,280 new cases will be diagnosed in the United States, with 1,280 people expected to die from CML. On average, most patients are diagnosed with CML around the age of 64 years, with almost half of cases coming from patients aged 65 years and older. Fifteen percent of all new leukemia cases are CML.²

Earlier in the year, data from ASC4FIRST were presented at the 2024 American Society of Clinical Oncology Annual Meeting, as a plenary at the European Hematology Association 2024 Congress and featured in The New England Journal of Medicine. Scemblix has been approved by a number of regulatory authorities for adult patients with Ph+ CML-CP who have been treated previously with two or more TKIs.¹

References

1. Novartis Scemblix® granted FDA Priority Review for the treatment of adults with newly diagnosed CML. Novartis. July 29, 2024. Accessed July 30, 2024. https://www.novartis.com/news/media-releases/novartis-scemblix-granted-fda-priority-review-treatment-adults-newly-diagnosed-cml

2. Key Statistics for Chronic Myeloid Leukemia. American Cancer Society. Accessed July 30, 2024. https://www.cancer.org/cancer/types/chronic-myeloid-leukemia/about/statistics.html#:~:text=About%201%20person%20in%20526,is%20rarely%20seen%20in%20children.