SCEMBLIX®▼ (asciminib) Prescribing information (external link)
GLIVEC® (imatinib mesilate) Prescribing information (external link)
SCEMBLIX®▼ (asciminib) is indicated for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs), and without a known T315I mutation.1
SCEMBLIX®▼(asciminib) mechanism of action (MoA)
SCEMBLIX® (asciminib) is the first and only STAMP inhibitor2,3
Learn how the unique MoA of SCEMBLIX supports its specificity in treating CML.2
Find out more about the efficacy of SCEMBLIX in ASCEMBL
SCEMBLIX® (asciminib) MoA
SCEMBLIX targets a different site on BCR-ABL1 compared to TKIs – the myristoyl pocket2–4
In people who do not have CML, the myristoyl pocket is occupied by the N-terminal portion of ABL1, maintaining the protein in an inactive conformation. In BCR-ABL1, the myristoyl pocket is vacant, activating the kinase.5,6
SCEMBLIX is a first-in-class STAMP inhibitor. Binding specifically to the myristoyl pocket, it potently inactivates BCR-ABL1 via allosteric inhibition.2
Click on the video below to find out more.
VIDEO
Why choose a different MoA?
Back-to-back use of a second generation TKI may provide limited benefit in patients with CP-CML who are resistant/intolerant to prior second generation TKI treatments8
A second generation TKI may have limited benefit in the 3L setting, after the failure of another second generation TKI and first generation TKI prior to that.9
In patients with CML, the 8-year overall survival (OS) was 22% (n=13) for those on ≥3L of treatment compared to 83% (n=55) for the patients maintained on imatinib as their 1L therapy*10
3L dasatinib: n=34 (after imatinib + nilotinib)
3L nilotinib: n=14 (after imatinib + dasatinib)
CP patients at 3L: n=25 (52%)
3L dasatinib: n=16 (after imatinib + nilotinib)
3L nilotinib: n=9 (after imatinib + dasatinib)
Accelerated phase (AP): n=10 (21%)
Blast phase: n=13 (27%)
BID: 70 mg (n=15), 50 mg (n=5), 120 mg (n=1)
QD: 140 mg (n=9), 100 mg (n=3), 50 mg (n=1)
BID: 400 mg (n=11)
QD: 800 mg (n=2), 400 mg (n=1)
Complete cytogenic response (CCyR): 11%
Major molecular response (MMR): 33%
CCyR: 31%
MMR: 13%
Identify prognostic factors for response and outcomes on 3L therapy
All in CP and had prior imatinib, followed by 2L dasatinib (n=20) or nilotinib (n=6)
3L drugs: dasatinib or nilotinib (switched from the other second‑generation TKI)
Time‑to‑event outcomes: OS, progression‑free survival (PFS) and EFS – definitions as in prior Imperial College CML work (EFS events included progression, loss of response, or death)
MCyR: n=13 (50.0%)
CCyR: n=9 (34.6%)
MMR: n=5 (19.2%)
CP: n=39
AP: n=21
Prior imatinib resistance or intolerance, and
Failure of dasatinib therapy (resistance or intolerance)
400 mg orally BID (on an empty stomach)
Dose escalation: Allowed up to 600 mg BID – used in 9 patients (7 CP, 2 AP)
MCyR = complete (CCyR, 0% Ph+) + partial (PCyR, <35% Ph+ metaphases)
MCyR: n=16 (43%)
CCyR: n=9 (24%)
Retrospective cohort analysis from a single centre (MD Anderson)11
Objective | Assessing responses and long‑term outcomes of using a second‑generation TKI (nilotinib or dasatinib) as 3L therapy after failure of imatinib plus one prior second‑generation TKI |
Population | Total patients with CML treated sequentially with 3 different TKIs: N=48 Disease phase at start of third TKI: |
Starting dose | Dasatinib: Nilotinib: Doses could be adjusted for toxicity as per institutional practice |
Endpoints | Cumulative response (each response grade) |
Median follow up from start of third TKI (total cohort) | 13 months |
Response in 3L | Patient receiving nilotinib in 3L (n=9): Patients receiving dasatinib in 3L (n=16): |
Retrospective/prospective cohort analysis (single center, Imperial College London)12
Objective | Assess efficacy of a 3L TKI (dasatinib or nilotinib) in CML patients still in first CP who had failed imatinib + one second‑generation TKI |
Population | Total patients: N=26 |
Starting dose | ‘Standard doses as described by others’ (i.e., typical CML–CP doses used in prior dasatinib/nilotinib trials) |
Endpoints | Major cytogenetic response (MCyR), CCyR, MMR For response analyses, patients who underwent allogeneic SCT (n=6) were censored at transplant for cytogenetic endpoints but not for EFS/PFS/OS |
Median follow up from start of third TKI (total cohort) | 21.5 months |
Response in 3L | Responses on 3L TKI (any time) (n=26): |
International, single‑arm, Phase II trial13
Population | Adults with Ph+ CML in: All had: |
Starting dose | Nilotinib: |
Endpoints | MCyR, CCyR, MMR |
Median follow up from start of third TKI (total cohort) | CP: 11 months |
Response in 3L | CP (n=37): |
Rates of CCyR for sequential second generation TKI use across different studies
In the absence of head-to-head studies, no comparisons can be made due to varying study designs, low population sizes and diverse patient demographics. However, following the review of the evidence, these studies are suggestive of low observed CCyR rates for sequential second generation TKI use.
With its unique MoA, SCEMBLIX offers a different approach for treating CML5–7
SCEMBLIX demonstrated superior efficacy vs bosutinib; MMR at week 24, 25.5% vs 13.2%, p=0.029, and was observed to demonstrate a more generally tolerable safety profile2
The most common adverse events of any grade (incidence ≥20%) in patients receiving SCEMBLIX were musculoskeletal pain (38.8%), upper respiratory tract infections (29.5%), fatigue (28.9%), thrombocytopenia (28.1%), headache (26.4%), arthralgia (24.4%), increased pancreatic enzymes (23%), diarrhoea (22.5%), abdominal pain (22.2%), rash (21.6%), hypertension (20.8%) and nausea (20.8%). Please see the Summary of Product Characteristics for further information.
*Data from a retrospective, single centre analysis of patients with CML who received one or more lines of ATP-competitive TKIs.10
1L, first-line; 2L, second-line; 3L, third-line; AP, accelerated phase; ATP, adenosine triphosphate; BCR-ABL1, breakpoint cluster Abelson region murine leukaemia viral oncogene homolog 1; BID, twice daily; CCyR, complete cytogenic response; CML, chronic myeloid leukaemia; CP, chronic phase; EFS, event-free survival; MCyR, major cytogenetic response; MMR, major molecular response; MoA, mechanism of action; OS, overall survival; PCyR, partial cytogenetic response; Ph+ CML, Philadelphia chromosome-positive chronic myeloid leukaemia; PFS, progression-free survival; QD, once daily; SCT, stem cell transplantation; STAMP, specifically targeting the ABL1 myristoyl pocket; TKI, tyrosine kinase inhibitor.
References:
SCEMBLIX (asciminib) Summary of Product Characteristics.
Réa D, et al. Blood 2021;138(21):2031–2041.
Schoepfer J, et al. J Med Chem 2018;61(18):8120–8135.
Redaelli S, et al. J Clin Oncol 2009;27(3):469–471.
Hughes TP, et al. N Engl J Med 2019;381(24):2315–2326.
Manley PW, et al. Leuk Res 2020;98:106458.
Iacob RE, et al. PLoS One 2011;6(1):e15929.
Lipton JH, et al. Leuk Res 2015;39:58–64.
Cortes JE, et al. J Hematol Oncol 2021;14:110.
Bosi GR, et al. HematolTransfus Cell Ther 2019;41:222–228.
Garg RJ, et al. Blood 2009;114:4361–4368.
Ibrahim AR, et al. Blood 2010;116:5497–5500.
Giles F J, et al. Leukemia 2010;24:1299–1301.
UK | February 2026 | FA-11555296-1
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis online through the pharmacovigilance intake (PVI) tool at www.novartis.com/report, or alternatively email [email protected] or call 01276 698370.
