SCEMBLIX

Treatment with Scemblix should be initiated by a physician knowledgeable in the diagnosis and treatment of patients with chronic myeloid leukaemia. Posology The recommended total daily dose of Scemblix is 80 mg. Scemblix can be taken orally either as 80 mg once daily at approximately the same time each day or as 40 mg twice daily at approximately 12-hour intervals.

Patients changing from 40 mg twice daily to 80 mg once daily should start taking asciminib once daily approximately 12 hours after the last twice-daily dose, and then continue at 80 mg once daily. Patients changing from 80 mg once daily to 40 mg twice daily should start taking asciminib twice daily approximately 24 hours after the last once-daily dose and then continue at 40 mg twice daily at approximately 12-hour intervals.

Any change in the dosage regimen is at the prescriber’s discretion, as necessary for the management of the patient.

Missed dose Once-daily dosage regimen:

If a dose is missed by more than approximately 12 hours, it should be skipped and the next dose should be taken as scheduled.

Twice-daily dosage regimen:

If a dose is missed by more than approximately 6 hours, it should be skipped and the next dose should be taken as scheduled. Treatment duration Treatment with asciminib should be continued as long as clinical benefit is observed or until unacceptable toxicity occurs.

Dose adjustments for adverse reactions For the management of adverse reactions, the dose can be reduced based on individual safety and tolerability, as described in Table 1. If adverse reactions are effectively managed, asciminib may be resumed as described in Table 1.

It should be permanently discontinued in patients unable to tolerate a total daily dose of 40 mg. Table 1 Asciminib dose modification Starting dose Reduced dose Resumed dose 80 mg once daily 40 mg once daily 80 mg once daily 40 mg twice daily 20 mg twice daily 40 mg twice daily The recommended dosage modification for the management of selected adverse reactions is shown in Table 2.

0 x 109/l and/or PLT <50 x 109/l Withhold asciminib until resolved to ANC ≥1 x 109/l and/or PLT ≥50 x 109/l. If resolved: • Within 2 weeks: resume at starting dose. • After more than 2 weeks: resume at reduced dose For recurrent severe thrombocytopenia and/or neutropenia, withhold asciminib until resolved to ANC ≥1 x 109/l and PLT ≥50 x 109/l, then resume at reduced dose.

Summary of the safety profile The overall safety profile of asciminib has been evaluated in 356 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.

In ASCEMBL, patients received asciminib as monotherapy at a dose of 40 mg twice daily. In X2101, patients received asciminib as monotherapy at doses ranging from 10 to 200 mg twice daily and 80 to 200 mg once daily. The safety pool (N=356) includes patients receiving asciminib at doses ranging from 10 to 200 mg twice daily and 80 to 200 mg once daily, with 156 patients receiving asciminib at 40 mg twice daily in the pivotal study, and 35 patients receiving 40 mg twice daily and 18 patients receiving 80 mg once daily from study X2101 as a starting dose.

1 to 349 weeks). 8%). 3%). 2% of patients receiving asciminib. 1%). The predicted safety profile of asciminib at the 80 mg once-daily dose is similar to the 40 mg twice-daily dose, based on exposure-safety analysis. Tabulated list of adverse reactions Adverse reactions from clinical studies (Table 3) 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 are defined as: 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 3 Adverse reactions observed with asciminib in clinical studies System organ class Frequency category Adverse reaction Very common Upper respiratory tract infection1 Infections and infestations Common Lower respiratory tract infection2, influenza Very common Thrombocytopenia3, neutropenia4, anaemia5 Blood and lymphatic system disorders Uncommon Febrile neutropenia, pancytopenia Immune system disorders Uncommon Hypersensitivity Very common Dyslipidaemia6 Metabolism and nutrition disorders Common Decreased appetite Nervous system disorders Very common Headache, dizziness Eye disorders Common Dry eye, vision blurred Cardiac disorders Common Palpitations Vascular disorders Very common Hypertension7 Very common Dyspnoea, coughRespiratory, thoracic and mediastinal disorders Common Pleural effusion, non-cardiac chest pain Very common Pancreatic enzymes increased8, vomiting, diarrhoea, nausea, abdominal pain9, , constipationGastrointestinal disorders Common Pancreatitis10 Very common Hepatic enzyme increased11 Hepatobiliary disorders Common Blood bilirubin increased12 Very common Rash13, pruritisSkin and subcutaneous tissue disorders Common Urticaria Musculoskeletal and connective tissue disorders Very common Musculoskeletal pain14, arthralgia General disorders and administration site conditions Very common Fatigue15, oedema16, pyrexia17 Investigations Common Electrocardiogram QT prolonged, blood creatine phosphokinase increased 1 Upper respiratory tract infection includes: upper respiratory tract infection, nasopharyngitis, pharyngitis and rhinitis.

Myelosuppression Thrombocytopenia, neutropenia and anaemia occurred in patients receiving asciminib. 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. 2). 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. 2). 2). 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. 1). 8). Hypertension should be monitored and managed using standard antihypertensive therapy during treatment with asciminib as clinically indicated.

Hepatitis B reactivation 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. Lactose Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially “sodium free”.

1.