Source: European Medicines Agency (EU) Revision Year: 2026 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In patients with Ph+ CML-CP with the T315I mutation treated with the 200 mg twice-daily dose, close monitoring should be considered since there are uncertainties regarding a potential increase of safety risks compared to the 80 mg total daily dose due to the small dataset of 48 patients, of whom 34 had a treatment intensity of >90%.
Thrombocytopenia, neutropenia and anaemia occurred in patients receiving asciminib. Severe (NCI CTCAE grade 3 or 4) thrombocytopenia and neutropenia were reported during treatment with asciminib (see section 4.8). Myelosuppression was generally reversible and managed by temporarily withholding treatment. Complete blood counts should be performed every two weeks for the first 3 months of treatment and then monthly thereafter, or as clinically indicated. Patients should be monitored for signs and symptoms of myelosuppression.
Based on the severity of thrombocytopenia and/or neutropenia, the dose should be temporarily withheld, reduced or permanently discontinued as described in Table 1 (see section 4.2).
Pancreatitis and asymptomatic elevations of serum lipase and amylase, including severe reactions, occurred in patients receiving asciminib (see section 4.8).
Serum lipase and amylase levels should be assessed monthly during treatment with asciminib, or as clinically indicated. Patients should be monitored for signs and symptoms of pancreatic toxicity. More frequent monitoring should be performed in patients with a history of pancreatitis. If serum lipase and amylase elevations are accompanied by abdominal symptoms, treatment should be temporarily withheld and appropriate diagnostic tests should be considered to exclude pancreatitis (see section 4.2).
Based on the severity of serum lipase and amylase elevations, the dose should be temporarily withheld, reduced or permanently discontinued as described in Table 1 (see section 4.2).
QT prolongation occurred in patients receiving asciminib (see section 4.8).
It is recommended that an electrocardiogram is performed prior to the start of treatment with asciminib, and monitored during treatment as clinically indicated. Hypokalaemia and hypomagnesaemia should be corrected prior to asciminib administration and monitored during treatment as clinically indicated.
Caution should be exercised when administering asciminib at a total daily dose of 80 mg concomitantly with medicinal products with known risk of torsades de pointes.
Concomitant administration of asciminib at 200 mg twice daily with medicinal products with a known risk of torsades de pointes should be avoided (see sections 4.5 and 5.1).
Hypertension, including severe hypertension, occurred in patients receiving asciminib (see section 4.8).
Hypertension and other cardiovascular risk factors should be monitored regularly and managed using the standard therapies during treatment with asciminib.
Reactivation of hepatitis B virus (HBV) has occurred in patients who are chronic carriers of this virus following administration of other BCR::ABL1 tyrosine kinase inhibitors (TKIs). Patients should be tested for HBV infection before the start of treatment with asciminib. HBV carriers who require treatment with asciminib should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy.
In the absence of clinical data, caution should be exercised when administering asciminib at 200 mg twice daily in patients with severe renal impairment (see sections 4.2 and 5.2).
In the absence of clinical data, caution should be exercised when administering asciminib at 200 mg twice daily in patients with severe hepatic impairment (see sections 4.2 and 5.2).
Equivalent efficacy of the different posologies has not been formally demonstrated in clinical studies. Clinical, pharmacokinetic and exposure-response modelling data in patients with Ph+ CML-CP previously treated with two or more TKIs suggest that the 40 mg twice-daily dose regimen might be more effective than the 80 mg once-daily dose regimen (see sections 5.1 and 5.2).
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially "sodium-free".
Caution should be exercised during concomitant administration of asciminib at a total daily dose of 80 mg and medicinal products with known risk of torsades de pointes, including, but not limited to, bepridil, chloroquine, clarithromycin, halofantrine, haloperidol, methadone, moxifloxacin or pimozide.
Concomitant administration of asciminib 200 mg twice daily with medicinal products with a known risk of torsades de pointes should be avoided (see section 5.1).
Caution should be exercised during concomitant administration of asciminib at 200 mg twice daily with strong CYP3A4 inhibitors, including, but not limited to, clarithromycin, telithromycin, troleandomycin, itraconazole, ketoconazole, voriconazole, ritonavir, indinavir, nelfinavir or saquinavir. Dose adjustment of asciminib is not required.
Co-administration of a strong CYP3A4 inducer (rifampicin) decreased asciminib AUCinf by 15% and increased Cmax by 9% in healthy subjects receiving a single asciminib dose of 40 mg. Co-administration of a strong CYP3A4 inducer (phenytoin) decreased asciminib AUCinf and Cmax by 34% and 22%, respectively, in healthy subjects receiving a single asciminib dose of 200 mg.
Caution should be exercised during concomitant administration of asciminib at all recommended doses with strong CYP3A4 inducers, including, but not limited to, carbamazepine, phenobarbital, phenytoin or St. John's wort (Hypericum perforatum), which may result in lower efficacy of asciminib.
Co-administration of asciminib with a CYP3A4 substrate (midazolam) increased midazolam AUCinf and Cmax by 28% and 11%, respectively, in healthy subjects receiving asciminib 40 mg twice daily.
Caution should be exercised during concomitant administration of asciminib at all recommended doses with CYP3A4 substrates known to have a narrow therapeutic index, including, but not limited to, the CYP3A4 substrates fentanyl, alfentanil, dihydroergotamine or ergotamine (see section 5.2). Dose adjustment of asciminib is not required.
Co-administration of asciminib with a CYP2C9 substrate (warfarin) increased S-warfarin AUCinf and Cmax by 41% and 8%, respectively, in healthy subjects receiving asciminib 40 mg twice daily.
Caution should be exercised during concomitant administration of asciminib at a total daily dose of 80 mg with CYP2C9 substrates known to have a narrow therapeutic index, including, but not limited to, phenytoin or warfarin (see section 5.2). Dose adjustment of asciminib is not required.
Concomitant administration of asciminib at 200 mg twice daily with CYP2C9-sensitive substrates and CYP2C9 substrates known to have a narrow therapeutic index should be avoided and alternative medicines should be considered (see section 5.2). If co-administration cannot be avoided, the CYP2C9 substrate dose should be reduced. If co-administration with warfarin cannot be avoided, the frequency of international normalised ratio (INR) monitoring should be increased as the anticoagulant effect of warfarin may be enhanced.
Based on physiologically-based pharmacokinetic (PBPK) modelling, caution should be exercised during concomitant administration of asciminib at all recommended doses with BCRP substrates, including, but not limited to, sulfasalazine, methotrexate and rosuvastatin. No clinical drug interaction study with BCRP was performed.
Co-administration of asciminib at 80 mg once daily with an OATP1B, CYP3A4 and P-gp substrate (atorvastatin) increased atorvastatin AUCinf and Cmax by 14% and 24%, respectively, in healthy subjects. Clinically relevant interactions between Scemblix and OATP1B substrates are unlikely to occur.
Caution should be exercised during concomitant administration of asciminib at all recommended doses with P-gp substrates known to have a narrow therapeutic index, including, but not limited to digoxin, dabigatran and colchicine (see section 5.2). Dose adjustment of asciminib is not required.
The pregnancy status of women of childbearing potential should be verified prior to starting treatment with asciminib.
Sexually-active women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) during treatment with asciminib and for at least 3 days after stopping treatment.
There are no or limited amount of data from the use of asciminib in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Asciminib is not recommended during pregnancy and in women of childbearing potential not using contraception. The patient should be advised of a potential risk to the foetus if asciminib is used during pregnancy or if the patient becomes pregnant while taking asciminib.
It is unknown whether asciminib/metabolites are excreted in human milk. There are no data on the effects of asciminib on the breast-fed newborn/infant or on milk production. Because of the potential for serious adverse reactions in the breast-fed newborn/infant, breast-feeding should be discontinued during treatment and for at least 3 days after stopping treatment with asciminib.
There are no data on the effect of asciminib on human fertility. In rat fertility studies, asciminib did not affect reproductive function in male and female rats. However, adverse effects on sperm motility and count were observed in rats at doses of 200 mg/kg/day (see section 5.3). The relevance for humans is not known.
Asciminib has no or negligible influence on the ability to drive and use machines. However, it is recommended that patients experiencing dizziness, fatigue or other undesirable effects (see section 4.8) with a potential impact on the ability to drive or use machines safely should refrain from these activities as long as the undesirable effects persist.
The most common adverse reactions of any grade (incidence ≥20%) in patients receiving asciminib were musculoskeletal pain (34.4%), thrombocytopenia (28.1%), fatigue (25.4%), upper respiratory tract infections (24.8%), headache (22.8%), neutropenia (21.8%), arthralgia (20.7%) and diarrhoea (20.7%).
The most common adverse reactions of ≥ grade 3 (incidence ≥5%) in patients receiving asciminib were thrombocytopenia (16.5%), neutropenia (13.8%), increased pancreatic enzymes (9.4%) and hypertension (9.2%).
Serious adverse reactions occurred in 9.9% of patients receiving asciminib. The most frequent serious adverse reactions (incidence ≥1%) were pleural effusion (1.6%), lower respiratory tract infections (1.6%), thrombocytopenia (1.3%), pancreatitis (1.1%) and pyrexia (1.1%).
The safety dataset for the 200 mg twice-daily dose is limited to 48 patients, of whom 34 had a treatment intensity of >90%.
The most common adverse reactions of any grade (incidence ≥20%) in patients receiving asciminib were musculoskeletal pain (41.7%), fatigue (35.4%), increased pancreatic enzymes (31.3%), diarrhoea (27.1%), nausea (27.1%), increased hepatic enzymes (25.0%), arthralgia (25.0%), cough (22.9%), thrombocytopenia (20.8%), vomiting (20.8%) and headache (20.8%).
The most common adverse reactions of ≥grade 3 (incidence ≥5%) in patients receiving asciminib were increased pancreatic enzymes (22.9%), thrombocytopenia (16.7%), neutropenia (12.5%), increased hepatic enzymes (10.4%), hypertension (8.3%), anaemia (6.3%), vomiting (6.3%) and abdominal pain (6.3%).
Serious adverse reactions occurred in 12.5% of patients receiving asciminib. The most frequent serious adverse reactions (incidence ≥1%) were abdominal pain (4.2%), vomiting (4.2%), lower respiratory tract infections (4.2%), constipation (2.1%), headache (2.1%), non-cardiac chest pain (2.1%) and pleural effusion (2.1%).
The overall safety profile of asciminib has been evaluated in 556 patients with Ph+ CML in chronic (CP) and accelerated (AP) phases in the pivotal phase III study A2301 (ASCEMBL) and the phase I study X2101, and with newly diagnosed Ph+ CML-CP in the pivotal phase III study J12301 (ASC4FIRST). In ASCEMBL (N=156), patients received asciminib as monotherapy at a dose of 40 mg twice daily. In X2101 (N=200), patients received asciminib as monotherapy at doses ranging from 10 to 200 mg twice daily and 80 to 200 mg once daily. Of these patients, 48 with the T315I mutation received asciminib 200 mg twice daily. In ASC4FIRST (N=200), patients received asciminib as monotherapy at a dose of 80 mg once daily. In the pooled dataset, the median duration of exposure to asciminib was 123.29 weeks (range: 0.1 to 439 weeks).
Adverse reactions from clinical studies (Table 2) are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000).
Table 2. Adverse reactions observed with asciminib in clinical studies:
| System organ class | Frequency category | Adverse reaction |
| Infections and infestations | Very common | Upper respiratory tract infection1 |
| Common | Lower respiratory tract infection2, influenza | |
| Blood and lymphatic system disorders | Very common | Thrombocytopenia3, neutropenia4, anaemia5 |
| Uncommon | Febrile neutropenia, pancytopenia | |
| Immune system disorders | Uncommon | Hypersensitivity |
| Endocrine disorders | Common | Hypothyroidism6 |
| Metabolism and nutrition disorders | Very common | Dyslipidaemia7 |
| Common | Decreased appetite, hyperglycaemia | |
| Nervous system disorders | Very common | Headache, dizziness |
| Eye disorders | Common | Dry eye, vision blurred |
| Cardiac disorders | Common | Palpitations |
| Vascular disorders | Very common | Hypertension8 |
| Respiratory, thoracic and mediastinal disorders | Very common | Cough |
| Common | Pleural effusion, dyspnoea, non-cardiac chest pain | |
| Gastrointestinal disorders | Very common | Pancreatic enzymes increased9, vomiting, diarrhoea, nausea, abdominal pain10, constipation |
| Common | Pancreatitis11 | |
| Hepatobiliary disorders | Very common | Hepatic enzyme increased12 |
| Common | Blood bilirubin increased13 | |
| Skin and subcutaneous tissue disorders | Very common | Rash14, pruritus |
| Common | Urticaria | |
| Musculoskeletal and connective tissue disorders | Very common | Musculoskeletal pain15, arthralgia |
| General disorders and administration site conditions | Very common | Fatigue16 |
| Common | Oedema17, pyrexia18 | |
| Investigations | Common | Blood creatine phosphokinase increased |
| Uncommon | Electrocardiogram QT prolonged |
1 Upper respiratory tract infection includes: upper respiratory tract infection, nasopharyngitis, pharyngitis and rhinitis.
2 Lower respiratory tract infections include: pneumonia, bronchitis and tracheobronchitis.
3 Thrombocytopenia includes: thrombocytopenia and platelet count decreased.
4 Neutropenia includes: neutropenia and neutrophil count decreased.
5 Anaemia includes: anaemia, haemoglobin decreased and normocytic anaemia.
6 Hypothyroidism includes hypothyroidism, autoimmune thyroiditis, blood thyroid stimulating hormone increased, autoimmune hypothyroidism and primary hypothyroidism.
7 Dyslipidaemia includes: hypertriglyceridaemia, blood cholesterol increased, hypercholesterolaemia, blood triglycerides increased, hyperlipidaemia and dyslipidaemia.
8 Hypertension includes: hypertension and blood pressure increased.
9 Pancreatic enzymes increased includes: lipase increased, amylase increased and hyperlipasaemia.
10 Abdominal pain includes: abdominal pain and abdominal pain upper.
11 Pancreatitis includes: pancreatitis and pancreatitis acute.
12 Hepatic enzymes increased includes: alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased, transaminases increased and hypertransaminasaemia.
13 Blood bilirubin increased includes: blood bilirubin increased, bilirubin conjugated increased and hyperbilirubinaemia.
14 Rash includes: rash, rash maculopapular and rash pruritic.
15 Musculoskeletal pain includes: pain in extremity, back pain, myalgia, bone pain, musculoskeletal pain, neck pain, musculoskeletal chest pain and musculoskeletal discomfort.
16 Fatigue includes: fatigue and asthenia.
17 Oedema includes: oedema and oedema peripheral.
18 Pyrexia includes: pyrexia and body temperature increased.
Thrombocytopenia occurred in 28.1% of patients receiving asciminib, with grade 3 and 4 reactions reported in 7% and 9.5% of patients, respectively. Among the patients with thrombocytopenia ≥ grade 3, the median time to first occurrence of reactions was 6 weeks (range: 0.14 to 64.14 weeks), with median duration of any occurring reaction of 1.57 weeks (95% CI, range: 1.14 to 2 weeks). 2% of patients receiving asciminib permanently discontinued due to thrombocytopenia, while asciminib was temporarily withheld in 12.6% of patients due to the adverse reaction.
Thrombocytopenia occurred in 20.8% of patients with the T315I mutation receiving asciminib, with grade 3 and 4 reactions reported in 16.7% of patients. Among the patients with thrombocytopenia ≥ grade 3, the median time to first occurrence of reactions was 8.36 weeks (range: 1.43 to 38.43 weeks), with median duration of any occurring reaction of 4.29 weeks (95% CI, range: 1.71 to 5.71 weeks). 2.1% of patients with the T315I mutation receiving asciminib permanently discontinued due to thrombocytopenia, while asciminib was temporarily withheld in 6.3% of patients due to the adverse reaction.
Neutropenia occurred in 21.8% of patients receiving asciminib, with grade 3 and 4 reactions reported in 7.6% and 6.3% of patients, respectively. Among the patients with neutropenia ≥ grade 3, the median time to first occurrence of reactions was 7.14 weeks (range: 0.14 to 180.14 weeks), with median duration of any occurring reaction of 1.86 weeks (95% CI, range: 1.29 to 2 weeks). 1.3% of patients receiving asciminib permanently discontinued due to neutropenia, while asciminib was temporarily withheld in 9.4% of patients due to the adverse reaction.
Neutropenia occurred in 16.7% of patients with the T315I mutation receiving asciminib, with grade 3 and 4 reactions reported in 12.5% of patients. Among the patients with neutropenia ≥ grade 3, the median time to first occurrence of reactions was 4.14 weeks (range: 0.14 to 16.57 weeks), with median duration of any occurring reaction of 2.86 weeks (95% CI, range: 1.57 to 4.57 weeks). 2.1% of patients with the T315I mutation receiving asciminib permanently discontinued due to neutropenia, while asciminib was temporarily withheld in 2.1% of patients due to the adverse reaction.
Anaemia occurred in 12.9% of patients receiving asciminib, with grade 3 reactions occurring in 4.1% of patients. Among the patients with anaemia ≥ grade 3, the median time to first occurrence of reactions was 24.14 weeks (range: 0.14 to 207 weeks), with median duration of any occurring reaction of 0.86 weeks (95% CI, range: 0.29 to 1.71 weeks). Asciminib was temporarily withheld in 0.5% of patients due to the adverse reaction.
Anaemia occurred in 10.4% of patients with the T315I mutation receiving asciminib, with grade 3 and 4 reactions reported in 6.3% of patients. Among the patients with anaemia ≥ grade 3, the median time to first occurrence of reactions was 38.43 weeks (range: 24.14 to 131 weeks), with median duration of any occurring reaction of 0.86 weeks (95% CI, range: 0.14 to NE [not estimable] weeks).
Pancreatitis occurred in 2% of patients receiving asciminib, with grade 3 reactions occurring in 1.1% of patients. 0.5% of patients receiving asciminib permanently discontinued due to pancreatitis, while asciminib was temporarily withheld in 1.1% of patients due to the adverse reaction. Asymptomatic elevations of serum lipase and amylase occurred in 19.8% of patients receiving asciminib, with grade 3 and 4 reactions occurring in 7.4% and 2% of patients, respectively. Of the patients with elevation of pancreatic enzymes, asciminib was permanently discontinued in 2% of patients due to the adverse reaction.
Pancreatitis occurred in 2.1% of patients with the T315I mutation receiving asciminib. Elevations of serum lipase and amylase occurred in 31.3% of patients with the T315I mutation receiving asciminib, with grade 3 and 4 reactions occurring in 22.9% of patients. 2.1% of patients with the T315I mutation receiving asciminib permanently discontinued due to elevation of pancreatic enzymes, while asciminib was temporarily withheld in 16.7% of patients due to the adverse reaction.
Electrocardiogram QT prolongation occurred in 0.9% of patients receiving asciminib. In the ASCEMBL clinical study, one patient had a prolonged QTcF greater than 500 milliseconds (ms) together with more than 60 ms QTcF increase from baseline, and one patient had prolonged QTcF with more than 60 ms QTcF increase from baseline.
Hypertension occurred in 17.1% of patients receiving asciminib, with grade 3 and 4 reactions reported in 9% and 0.2% of patients, respectively. Among the patients with hypertension ≥ grade 3, the median time to first occurrence of reactions was 40.14 weeks (range: 0.14 to 365 weeks). Asciminib was temporarily withheld in 0.9% of patients due to the adverse reaction.
Hypertension occurred in 14.6% of patients with the T315I mutation receiving asciminib, with grade 3 and 4 reactions reported in 8.3% of patients. Among the patients with hypertension ≥ grade 3, the median time to first occurrence of reactions was 32.64 weeks (range: 11.14 to 277.3 weeks), with median duration of any occurring reaction of 7.57 weeks (95% CI, range: 2.14 to NE weeks).
In the ASCEMBL study, decrease in phosphate levels occurred as a laboratory abnormality in 17.9% (all grades) and 7.1% (grade ¾) of 156 patients receiving asciminib at 40 mg twice daily. In the ASC4FIRST study, decrease in phosphate levels based on normal ranges occurred as a laboratory abnormality in 20.5% (all grades) of 200 patients receiving asciminib at 80 mg once daily.
In the X2101 study, decrease in phosphate levels occurred as a laboratory abnormality in 47.9% (all grades) and 8.3% (grade ¾) of 48 patients receiving asciminib at 200 mg twice daily.
Increases in ALT, AST and bilirubin levels occurred as laboratory abnormalities in 50%, 37.5% and 25% (all grades) of 48 patients receiving asciminib at 200 mg twice daily, respectively. Among these patients, increased ALT ≥ grade 3 events and increased AST ≥ grade 3 events were reported in 8.3% and 2.1% of patients, respectively.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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