Scemblix Shows Improved Major Molecular Response Treating Newly Diagnosed Philadelphia Chromosome-Positive Chronic Myeloid Leukemia

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Novartis announced promising results from the Phase III ASC4FIRST trial of Scemblix (asciminib), which showed superiority over standard-of-care tyrosine kinase inhibitors (TKIs) in treating newly diagnosed adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP).

“Patients living with CML need efficacious and well-tolerated treatment options that help them achieve meaningful outcomes as they manage their chronic condition,” said Shreeram Aradhye, MD, president, development, chief medical officer, Novartis, in a press release. “The compelling ASC4FIRST data highlight the potential of Scemblix to achieve better results than standard-of-care in newly diagnosed adults, while maintaining a favorable safety and tolerability profile. These results reinforce Scemblix as a proven treatment in Ph+CML-CP, as we continue to build on our 20-year legacy in CML innovation.”

ASC4FIRST (NCT04971226) is a head-to-head, multi-center, open-label, randomized study of oral Scemblix. Investigators enrolled 405 adult patients with newly diagnosed Ph+ CML-CP, who were randomly assigned to receive Scemblix at a dose of 80 mg QD compared with investigator-selected, standard-of-care (SoC) first- or second-generation TKIs, which included imatinib, nilotinib, dasatinib, or bosutinib. The trial’s dual primary endpoints were an efficacy comparison of Scemblix vs. investigator-selected TKIs, and to compare the efficacy of Scemblix with imatinib, based on proportion of patients achieving major molecular response (MMR) at week 48.

The results show that Scemblix demonstrated superior MMR rates at week 48 compared to imatinib, nilotinib, dasatinib, and bosutinib, achieving one of the trial’s primary endpoints. Additionally, Scemblix demonstrated a favorable safety and tolerability profile, leading to fewer adverse events and treatment discontinuations compared to both imatinib and second-generation TKIs.

“Scemblix is the first CML treatment to show significantly better efficacy compared to investigator-selected standard-of-care TKIs,” prof. Tim Hughes, MD, South Australian Health & Medical Research Institute, said in the release. “When you combine superior response with the excellent safety and tolerability profile of Scemblix, we have a very promising potential frontline option for newly diagnosed patients to support them in achieving their treatment goals.”

The median follow-up was 16.3 and 15.7 months for Scemblix and investigator-selected SoC TKIs, respectively. Investigators found that approximately 20% more patients administered Scemblix achieved MMR at week 48 compared with investigator-selected SoC TKIs. Further, approximately 30% more patients achieved MMR at week 48 compared with imatinib monotherapy.

Additionally, Scemblix produced deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs and imatinib monotherapy.

Overall, 67.7% of those treated with Scemblix achieved MMR compared to 49% for the SoC TKIs. Scemblix achieved a 69.3% MMR compared to imatinib, which achieved 40.2%.

The trial is ongoing, with the next analysis expected to occur after 96 weeks, aiming to determine the results of secondary endpoints. These data have been submitted to the FDA, with the findings also scheduled to be presented at the European Hematology Association 2024 Congress, scheduled for June.¹

“CML is a chronic condition, and the side effects of standard-of-care can be challenging for patients. They often affect their daily life and can lead to high rates of treatment switching,” said Gerald Clements, CML caregiver, patient advocate, Steering Committee Treasurer, CML Advocates Network, in the press release. “Effective care that can be tolerated long-term is a key unmet need. By potentially bringing Scemblix to patients when they are first diagnosed, they may have an opportunity to be on a highly effective treatment while also maintaining their day-to-day from the start.”

References

Novartis Scemblix® Phase III data first to show superior efficacy with a favorable safety and tolerability profile vs. standard-of-care TKIs in adults with newly diagnosed CML. Novartis. May 31, 2024. Accessed May 31, 2024. https://www.novartis.com/news/media-releases/novartis-scemblix-phase-iii-data-first-show-superior-efficacy-favorable-safety-and-tolerability-profile-vs-standard-care-tkis-adults-newly-diagnosed-cml