Scemblix Adverse Reactions

Summary of the safety profile: The overall safety profile of asciminib was investigated in 556 patients with Ph+ CML. In the pooled data set of the phase III pivotal study J12301 (ASC4FIRST) (N=200 newly diagnosed Ph+ CML‑CP patients) (80 mg once daily dosage), the phase III pivotal study A2301 (ASCEMBL) (N=156 Ph+ CML‑CP patients previously treated with two or more TKIs) (40 mg twice-daily dosage) and the phase I study X2101, the median duration of exposure to asciminib was 83.2 weeks (range: 0.1 to 439 weeks), with 79.3% of patients having been exposed for at least 48 weeks and 42.4% of patients having been exposed for at least 96 weeks.
The most common adverse drug reactions of any grade (incidence ≥20%) in patients receiving Scemblix were musculoskeletal pain (32.9%), thrombocytopenia (28.1%), fatigue (25%), upper respiratory tract infections (23.7%), headache (21.8%), neutropenia (21.6%) and diarrhoea (20%).
The most common adverse drug reactions of ≥ grade 3 (incidence ≥5%) in patients receiving Scemblix were thrombocytopenia (16.5%), neutropenia (13.7%), increased pancreatic enzymes (9.4%) and hypertension (8.6%).
Serious adverse drug reactions occurred in 9.5% of patients receiving Scemblix.
The most common serious adverse drug reactions (incidence ≥1%) were pleural effusion (1.6%), lower respiratory tract infections (1.4%), thrombocytopenia (1.3%), pancreatitis (1.1%) and pyrexia (1.1%).
List of adverse drug reactions: Adverse drug reactions are ordered by MedDRA system organ class and frequency according to 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). (See Table 5.)

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In the ASCEMBL study a decrease in phosphate levels occurred as a laboratory abnormality in 17.9% (all grades) and 7.1% (grade 3/4) of 156 patients receiving Scemblix at 40 mg twice daily. In the ASC4FIRST study a decrease in phosphate levels based on the normal range occurred as a laboratory abnormality in 13% (all grades) of 200 patients receiving Scemblix at 80 mg once daily. A decrease in phosphate levels occurred as a laboratory abnormality in 47.9% (all grades) and 8.3% (grade 3/4) of 48 patients who received Scemblix at a dose of 200 mg twice daily.
An increase in potassium as a laboratory abnormality was observed with asciminib in 22.5% (all grades) and 1.3% (grade 3/4) of 556 participants in the asciminib safety pool.
Description of specific adverse effects and additional information: Myelosuppression: Thrombocytopenia occurred in 156 of 556 (28.1%) patients receiving Scemblix, with grade 3 and 4 adverse drug reactions reported in 39 (7%) and 53 (9.5%) patients, respectively. Among the patients with ≥ grade 3 thrombocytopenia the median time to first occurrence of adverse drug reactions was 6 weeks (range: 0.14 to 64.14 weeks) with a median duration of an occurring adverse drug reaction of 1.57 weeks (95% CI, range: 1.14 to 2 weeks). Scemblix was permanently discontinued in 11 (2%) patients, while it was temporarily withheld in 70 (12.6%) patients due to thrombocytopenia.
Neutropenia occurred in 120 of 556 (21.6%) patients receiving Scemblix treatment, with grade 3 and 4 adverse drug reactions reported in 41 (7.4%) and 35 (6.3%) patients, respectively. Among the patients with ≥ grade 3 neutropenia the median time to first occurrence of adverse drug reactions was 7.07 weeks (range: 0.14 to 180.14 weeks) with a median duration of an occurring adverse drug reaction of 1.86 weeks (95% CI, range: 1.29 to 2 weeks). Scemblix was permanently discontinued in 7 (1.3%) patients, while it was temporarily withheld in 52 (9.4%) patients due to neutropenia.
Anaemia occurred in 70 of 556 (12.6%) patients receiving Scemblix, with grade 3 adverse drug reactions occurring in 22 (4%) patients. Among the patients with grade ≥3 anaemia the median time to first occurrence of adverse drug reactions was 22.21 weeks (range: 0.14 to 207 weeks) with a median duration of an occurring adverse drug reaction of 0.79 weeks (95% CI, range: 0.29 to 1.71 weeks). Scemblix was temporarily withheld in 2 patients (0.4%) due to anaemia.
Reporting suspected adverse effects after authorisation of the medicinal product is very important. It allows continued monitoring of the risk-benefit ratio of the medicinal product. Healthcare professionals are asked to report any suspected new or serious adverse effects.