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Priority Review based on ASC4FIRST Phase III study with Scemblix® data first to show significantly improved molecular response and a favorable safety and tolerability profile compared to standard of care therapies (imatinib and 2G TKIs)1
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Treatment options combining high efficacy with safety and tolerability represent a critical gap in care for long-term CML management1
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Scemblix was previously granted FDA Breakthrough Therapy designation and is in review under the agency’s Real-Time Oncology Review program2-4
East Hanover, July 29, 2024 – Novartis announced today that Scemblix® (asciminib) has been granted Priority Review status by the US Food and Drug Administration (FDA) for treatment of newly diagnosed adult patients with Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP).
The FDA grants Priority Review to medicines that address serious or life-threatening diseases or conditions and, if approved, would provide significant improvements in treatment safety or efficacy5. Scemblix previously received Breakthrough Therapy designation for the treatment of newly diagnosed adult patients and is currently being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program. Scemblix received Priority Review and Breakthrough Therapy designations at the time of the original new drug application for the treatment of adult patients with Ph+ CML-CP who have previously been treated with two or more TKIs2-4,6,7.
“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, Senior Vice President, Therapeutic Area Head, US Oncology, Novartis. "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.”
Priority Review designation is based on results from ASC4FIRST, a Phase III study that evaluated the efficacy, tolerability and safety of once daily Scemblix against investigator-selected (IS) tyrosine kinase inhibitors (TKIs) (imatinib, nilotinib, dasatinib, and bosutinib) representing the current standard of care (SoC) in newly diagnosed adult patients with Ph+ CML-CP1. Scemblix demonstrated superior major molecular response (MMR) rates in both primary endpoints at week 48 vs. IS SoC TKIs (68% vs. 49.0%) and imatinib alone (69% vs. 40%)1. Additionally, Scemblix is the first CML treatment to show superior efficacy along with a favorable safety and tolerability profile vs. imatinib and 2G TKIs, with fewer grade ≥3 AEs (38% vs. 44% and 55%), dose adjustments (30% vs. 39% and 53%) and half the rate of AEs leading to treatment discontinuation (5% vs. 11% and 10%)1. In newly diagnosed patients, the safety profile was consistent with previous registration studies, with no new safety concerns observed1.
Earlier this year, ASC4FIRST data were presented as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, as a plenary at the European Hematology Association (EHA) 2024 Congress and published in The New England Journal of Medicine1.
Scemblix is currently approved by the FDA, European Medicines Agency and other regulatory authorities for adult patients with Ph+ CML-CP who have been treated previously with two or more TKIs2,4,6.
About ASC4FIRST Phase III Clinical Trial
ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix® 80 mg QD vs. investigator-selected first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP6. The two primary endpoints of the study are to compare efficacy of asciminib vs. investigator-selected SoC TKIs and to compare efficacy vs. that of TKI within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients that achieve MMR at week 486.
The study remains ongoing with key secondary endpoints of proportion of patients that achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE (TTDAE) by week 966. The study also assesses additional secondary safety and efficacy endpoints, including MMR, MR4, MR4.5, complete hematological response (CHR) 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 survival6.
About Scemblix® (asciminib)
Scemblix® is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)8-10. The current approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive)10.
Scemblix is approved in more than 70 countries, including the US, the EU and JP, to treat adults with Ph+ CML-CP who have previously been treated with two or more TKIs2,3,7. In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation2-4.
Scemblix is an important treatment option for patients who experience resistance and/or intolerance after two prior TKI therapies11-26, and it is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination6,8,9,19,27-39.
About Novartis Commitment to CML
Novartis has a long-standing scientific commitment to patients living with CML. For more than two decades, our bold science has helped transform CML from a life-limiting to a chronic condition for many patients. Despite these advancements, there’s still work to be done. We continue to research ways to target the disease more selectively and to address the challenges of not reaching treatment efficacy goals, experiencing treatment resistance and/or intolerance that many patients face. Our legacy inspires our future innovation – we continue to lead the way in developing novel medicines to address serious unmet needs in CML. Our commitment also goes beyond science. Our 20+ year collaboration with the Max Foundation has provided access to Gleevec (imatinib), Tasigna (nilotinib) and now Scemblix and is delivering tremendous patient impact in low- and middle-income countries, with over 100,000 patients supported to date.
About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide.
References
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2.Scemblix. US FDA Prescribing Information. Novartis Pharmaceuticals; 2021.
3.Novartis data on file.
4.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Chronic Myeloid Leukemia Version 2.2024. December 5, 2023. Accessed April 3, 2024. https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf
5.U.S. Food and Drug Administration. Delivering Promising New Medicines Without Sacrificing Safety and Efficacy. August 27, 2019. Accessed July 17, 2024. https://www.fda.gov/news-events/fda-voices/delivering-promising-new-medicines-without-sacrificing-safety-and-efficacy.
6.A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP (ASC4FIRST). ClinicalTrials.gov identifier: NCT04971226. Updated March 25, 2024. Accessed March 26, 2024. https://clinicaltrials.gov/study/NCT04971226
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22.Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial. J Clin Oncol. 2016;34:2333-2340. doi:10.1200/JCO.2015.64.8899
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29.Hughes TP, et al. Expanded Phase 1 Study of ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Reveals Significant and Durable Responses in Patients with CML-Chronic Phase with Failure of Prior TKI Therapy. Presented at: ASH Annual Meeting & Exposition; Dec. 5, 2016.
30.Ottmann OG, Alimena G, DeAngelo DJ, et al. ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Exhibits Safety and Promising Single- Agent Activity in a Phase I Study of Patients with CML with Failure of Prior TKI Therapy. Blood. 2015;126(23):138. doi:10.1182/blood.V126.23.138.138
31.Mauro MJ, Kim DW, Cortes J, et al. Combination of Asciminib Plus Nilotinib (NIL) or Dasatinib (DAS) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Presented at: EHA Annual Meeting; June 15, 2019.
32.Cortes JE, Lang F, Kim DW, et al. Combination Therapy Using Asciminib Plus Imatinib (IMA) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Presented at: EHA Annual Meeting; June 15, 2019.
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34.Study of Efficacy of CML-CP Patients Treated with ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs. ClinicalTrials.gov identifier: NCT03106779. Updated February 7, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT03106779
35.Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and WithoutT315I Mutation (AIM4CML). ClinicalTrials.gov identifier: NCT04666259. Updated September 7, 2023. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT04666259
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39.Asciminib Treatment Optimization in ≥ 3rd Line CML-CP. ClinicalTrials.gov identifier: NCT04948333. Updated February 28, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT04948333