FDA approves Novartis Scemblix (asciminib), with novel mechanism of action for the treatment of chronic myeloid leukemia

- Scemblix nearly doubled the MMR rate vs. Bosulif??(bosutinib)* at 24 weeks (25% vs. 13% [P=0.029])
- The proportion of patients who discontinued treatment due to adverse reactions was more than three times lower in the Scemblix arm (n = 156) vs. patients in the Bosulif arm (n = 76) (7% vs. 25%)
- The most common (incidence = 20%) adverse reactions and laboratory abnormalities in the Scemblix arm were, respectively: upper respiratory tract infections and musculoskeletal pain; decrease in platelet and neutrophil counts, decrease in hemoglobin; increase in triglycerides, creatine kinase and alanine aminotransferase (ALT)
- Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.
- Rea D, et al. A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After= 2 Prior TKIs.?Blood. 2021. DOI: 10.1182/blood.2020009984. PMID: 34407542.
- Novartis Data on File, 2021.
- Cortes JE, et al. Asciminib, a First-in-Class STAMP Inhibitor, Provides Durable Molecular Response in Patients (pts) with Chronic Myeloid Leukemia (CML) Harboring the T315I Mutation: Primary Efficacy and Safety Results from a Phase 1 Trial. Oral presentation at: ASH Annual Meeting; Dec. 7, 2020
- Wylie AA, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR?ABL1.?Nature. 2017;543(7647):733-737.
- Schoepfer J, et al. Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1.?J Med Chem. 2018;61(18):8120-8135.
- Hughes TP, et al. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019; 381(24):2315-2326.
- 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. Poster presented at: ASH Annual Meeting & Exposition; Dec. 5, 2016.
- Ottmann OG, 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.
- Mauro MJ, 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. Poster presented at: EHA Annual Meeting; June 15, 2019.
- Cortes JE, et al. Combination Therapy Using Asciminib Plus Imatinib (IMA) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Poster presented at: EHA Annual Meeting; June 15, 2019.
- ClinicalTrials.gov. 2017. Study of Efficacy of CML-CP Patients Treated with ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs. [online] Available at:?https://clinicaltrials.gov/ct2/show/NCT03106779.
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- ClinicalTrials.gov. 2020. Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and WithoutT315I Mutation (AIM4CML). [online] Available at:?https://clinicaltrials.gov/ct2/show/NCT04666259.
- ClinicalTrials.gov. 2018. Study of Efficacy And Safety Of Asciminib In Combination With Imatinib In Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP). [online] Available at:?https://clinicaltrials.gov/ct2/show/NCT03578367.
- ClinicalTrials.gov. 2021. Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors. [online] Available at:?https://clinicaltrials.gov/ct2/show/NCT04795427.
- ClinicalTrials.gov. 2014. A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL. [online] Available at:?https://clinicaltrials.gov/ct2/show/NCT02081378.
- ClinicalTrials.gov. 2021 Asciminib Treatment Optimization in = 3rd Line CML-CP. [online] Available at:?https://clinicaltrials.gov/ct2/show/NCT04948333
- Flis S, et al. Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities.?Drug Des Devel Ther.?2019;13:825-843.
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- Cortes JE, et al. Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib.?Am J Hematol.?2016;91(12):1206-1214.
- Cortes JE, et al. Ponatinib efficacy and safety in Philadelphia chromosome?positive leukemia: Final 5-yearresults of the phase 2 PACE trial.?Blood. 2018;132(4):393-404.
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- Giles FJ, et al. Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy. Leukemia. 2010; 24(7):1299?1301.
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- Shah NP, et al. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib.?Haematologica. 2010;95:232-240
- Gambacorti-Passerini C., et al. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up.?Am J Hematol.?2014;89:732-742.
- Manley P., et al. The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase.?Leukemia Research. 2020;98
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