{"entity":{"id":"asciminib","kind":"drug","name":"Asciminib","aka":[],"tldr":"Asciminib is a BCR::ABL1 blocker that binds a different pocket from every other TKI, approved for all newly diagnosed chronic myeloid leukaemia in 2024 and now being tested in Ph-positive ALL.","summary":"Binds the myristoyl pocket (STAMP), so it works against ATP-site resistance mutations and combines with ATP-competitive TKIs. ASCEMBL (third line) and ASC4FIRST (frontline CML: MMR at 48 weeks 67.7% vs 49.0% for investigator-selected TKIs) led to approvals in 2021 and October 2024. Trials combine asciminib with dasatinib or ponatinib and with blinatumomab in Ph+ ALL to pre-empt resistance. Included here because Ph+ ALL shares the target.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Asciminib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Asciminib"}],"tags":[],"related":["bcr-abl1-t315i"],"cancers":["all-leukemia","cml-chronic-phase"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["bcr-abl","abl1"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["ph-positive-all"],"trials":["nct07354074","nct06514534","nct04971226","nct04925479","nct05384587","nct05456191","nct07387926"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Approved indications are in chronic myeloid leukaemia; Ph+ ALL use is investigational."],"brand":"Scemblix","modality":"Small-molecule allosteric ABL1 inhibitor (STAMP)","mechanism":"Allosteric inhibitor locking ABL1 in an inactive conformation via the myristoyl pocket; active against T315I at higher dose.","approvals":[{"region":"US","year":2021,"indication":"CML after ≥2 prior TKIs; T315I CML"},{"region":"US","year":2024,"indication":"Newly diagnosed Ph+ CML in chronic phase (ASC4FIRST)"}],"mechanismSteps":["Asciminib occupies the myristoyl pocket, mimicking the natural auto-inhibitory switch","ABL1 is locked inactive regardless of ATP-site mutations","Combination with an ATP-site TKI blocks two independent escape routes"],"dosing":{"route":"Oral","schedule":"CML: 80 mg once daily or 40 mg twice daily; 200 mg twice daily for T315I","monitoring":"Pancreatic enzymes, blood pressure, myelosuppression","source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Scemblix"},"toxicity":[{"event":"Thrombocytopenia","grade3PlusPct":17,"source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Scemblix"},{"event":"Hypertension","anyGradePct":13},{"event":"Pancreatic enzyme elevation","anyGradePct":13}],"access":[],"regulatoryEvents":[{"date":"2021-10-29","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs)"},{"date":"2022-10-12","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2021 converted to traditional approval 1.0 year after it was granted.","indication":"Adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs)"},{"date":"2024-10-29","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 1.9 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-asciminib-newly-diagnosed-chronic-myeloid-leukemia","indication":"Treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP)."}]},"route":"/drugs/asciminib/","neighbours":{"biomarker":[{"id":"bcr-abl1-t315i","kind":"biomarker","name":"BCR::ABL1 T315I","route":"/biomarkers/bcr-abl1-t315i/"},{"id":"bcr-abl1-transcript","kind":"biomarker","name":"BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)","route":"/biomarkers/bcr-abl1-transcript/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"cml","kind":"cancer","name":"Chronic myeloid leukaemia (CML)","route":"/cancers/cml/"},{"id":"cml-advanced-phase","kind":"cancer","name":"Chronic myeloid leukaemia, accelerated and blast phase","route":"/cancers/cml-advanced-phase/"},{"id":"cml-chronic-phase","kind":"cancer","name":"Chronic myeloid leukaemia, chronic phase","route":"/cancers/cml-chronic-phase/"},{"id":"all-paediatric-ph-positive","kind":"cancer","name":"Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)","route":"/cancers/all-paediatric-ph-positive/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"abl1","kind":"target","name":"ABL1","route":"/targets/abl1/"},{"id":"bcr-abl","kind":"target","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/targets/bcr-abl/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"term":[{"id":"abl1-kinase-domain-mutations","kind":"term","name":"BCR::ABL1 kinase domain mutations (T315I and others)","route":"/terms/abl1-kinase-domain-mutations/"},{"id":"molecular-response","kind":"term","name":"Molecular response (MMR, MR4, treatment-free remission)","route":"/terms/molecular-response/"},{"id":"gatekeeper-mutation","kind":"term","name":"On-target resistance mutations (gatekeeper, solvent-front, compound)","route":"/terms/gatekeeper-mutation/"},{"id":"ph-positive-all","kind":"term","name":"Ph-positive ALL","route":"/terms/ph-positive-all/"},{"id":"philadelphia-chromosome","kind":"term","name":"Philadelphia chromosome (Ph+, BCR::ABL1)","route":"/terms/philadelphia-chromosome/"},{"id":"sokal-elts-scores","kind":"term","name":"Sokal and ELTS risk scores (chronic myeloid leukaemia)","route":"/terms/sokal-elts-scores/"}],"trial":[{"id":"nct04971226","kind":"trial","name":"A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP","route":"/trials/nct04971226/"},{"id":"nct05456191","kind":"trial","name":"A Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)","route":"/trials/nct05456191/"},{"id":"nct05384587","kind":"trial","name":"Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia","route":"/trials/nct05384587/"},{"id":"nct06514534","kind":"trial","name":"Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.","route":"/trials/nct06514534/"},{"id":"nct07387926","kind":"trial","name":"Safety and Efficacy of Asciminib in Pediatrics and Young Adults With Relapse/Refractory (r/r) Philadelphia Positive (Ph+) or ABL-class Ph-like Acute Lymphoblastic Leukemia (ALL)","route":"/trials/nct07387926/"},{"id":"nct04925479","kind":"trial","name":"Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia","route":"/trials/nct04925479/"},{"id":"nct07354074","kind":"trial","name":"Study to Determine the Efficacy and Safety of Asciminib in Pediatric Patients With Ph+ CML-CP","route":"/trials/nct07354074/"}],"pathway":[{"id":"bcr-abl1-signalling","kind":"pathway","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/pathways/bcr-abl1-signalling/"},{"id":"cml-signalling","kind":"pathway","name":"Chronic myeloid leukaemia (KEGG map)","route":"/pathways/cml-signalling/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"}],"paper":[{"id":"paper-iris-imatinib-nejm-2003","kind":"paper","name":"IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia","route":"/key-papers/paper-iris-imatinib-nejm-2003/"}]}}