FDA Grants Accelerated Approval to Novartis’ Scemblix for Newly Diagnosed Chromosome-Positive Chronic Myeloid Leukemia

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The FDA has granted accelerated approval to Novartis’ Scemblix (asciminib) for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). According to the company, the approval was based on major molecular response rate (MMR) at week 48 from the ASC4FIRST Phase III, which found that Scemblix was superior to standard-of-care (SOC) tyrosine kinase inhibitors (TKIs) in achieving MMR rates at week 48.¹

“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,” said Lee Greenberger, PhD, chief scientific officer, the Leukemia & Lymphoma Society, in a press 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.”

ASC4FIRST is a head-to-head, multi-center, open-label, randomized study of oral Scemblix compared to first- or second-generation TKIs. Consisting of 405 patients, the dual primary endpoints were to compare the efficacy of Scemblix vs. TKIs and to compare the efficacy compared to that of TKIs within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients who achieve MMR at week 48. The secondary endpoints, which are currently in progress, are proportion of patients who achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an adverse event (AE) by week 96.

Results found that 68% of patients achieved MMR compared to 49% for SOC TKIs. Additionally, 69% achieved MMR compared to 40% for imatinib alone at week 48. Further, patients treated with Scemblix achieved a 41% rate of molecular responses by week 48, while the TKI group and imatinib alone group achieved 22% and 16%, respectively.

The safety profile for Scemblix was consistent with previous studies, and no new safety concerns were identified. Common AEs included musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain and diarrhea.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, Georgia Cancer Center, in the press release. “In the first-of-its-kind ASC4FIRST trial, Scemblix achieved impressive results across all three parameters of efficacy, safety and tolerability versus all standard of care TKIs. This Scemblix data has the potential to be practice-changing.”

According to the American Cancer Society, around 15% of all new cases of leukemia in the United States are CML. It is also estimated that by the end of 2024, 9,280 new cases of CML will be diagnosed, with around 1,280 deaths. Approximately one in every 526 people in the United States will be diagnosed with CML in their lifetime.²

“We are proud to help redefine CML treatment once again with Scemblix, as we continue to deliver on our 20+ year commitment to innovation and support in CML,” said Victor Bulto, president, US, Novartis, in the press release. “Despite many advances in the field, patients still need treatment options that are highly effective with a favorable tolerability profile to help enable them to achieve meaningful outcomes as they manage chronic conditions. With this approval, we can offer newly diagnosed adult Ph+ CML-CP patients a new treatment option that combines both, with the potential to change the trajectory of many more people living with CML.”

References

1. Novartis Scemblix® FDA approved in newly diagnosed CML, offering superior efficacy, and favorable safety and tolerability profile. Novartis. October 29, 2024. Accessed October 30, 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. Key Statistics for Chronic Myeloid Leukemia. American Cancer Society. Accessed October 30, 2024. https://www.cancer.org/cancer/types/chronic-myeloid-leukemia/about/statistics.html#:~:text=About%2015%25%20of%20all%20new,CML%20is%20around%2064%20years.