Bacrelba Adverse Reactions

Summary of the safety profile: The overall safety profile of Asciminib (Bacrelba) has been evaluated in 556 patients with Ph+ CML in chronic (CP) and accelerated (AP) phases receiving Asciminib (Bacrelba) as monotherapy. It is based on the safety pool of the pivotal phase III study J12301 (ASCAFIRST) (N=200 newly diagnosed Ph+ CML-CP patients), the pivotal phase III study A2301 (ASCEMBL) (N=156 Ph+ CML-CP patients previously treated with two or more TKIs) and the phase I study X2101, including patients with: Previously treated Ph+ CML-CP (N=115), Ph+ CML-CP harboring the T315I mutation (N=70), Ph+ CML-AP (N=15).
The safety pool (N=556) includes patients receiving Asciminib (Bacrelba) at doses ranging from 10 to 200 mg twice daily and 80 to 200 mg once daily. In the pooled dataset, the median duration of exposure to Asciminib (Bacrelba) was 83.29 weeks (range: 0.1 to 439 weeks), with 79.3% of patients exposed for at least 48 weeks and 42.4% of patients exposed for at least 96 weeks, respectively.
The most common adverse drug reactions of any grade (incidence ≥20%) in patients receiving Asciminib (Bacrelba) 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 Asciminib (Bacrelba) 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 Asciminib (Bacrelba).
The most frequent 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%).
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions from clinical studies (Table 5 and Table 6) are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): 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, decrease in phosphate levels occurred as a laboratory abnormality in 17.9% (all grades) and 7.1% (grade 3/4) of 156 patients receiving Asciminib (Bacrelba) at 40 mg twice daily. In the ASCAFIRST study, decrease in phosphate levels based on normal ranges occurred as a laboratory abnormality in 13% (all grades) of 200 patients receiving Asciminib (Bacrelba) at 80 mg once daily. (See Table 6.)

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Decrease in phosphate levels occurred as a laboratory abnormality in 47.9% (all grades) and 8.3% (grade 3/4) of 48 patients receiving Asciminib (Bacrelba) at 200 mg twice daily.
Description of selected adverse drug reactions: Myelosuppression: Thrombocytopenia occurred in 156 of 556 (28.1%) patients receiving Asciminib (Bacrelba), with grade 3 and 4 reactions reported in 39 (7%) and 53 (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). Asciminib (Bacrelba) 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 Asciminib (Bacrelba), with grade 3 and 4 reactions reported in 41 (7.4%) and 35 (6.3%) patients, respectively. Among the patients with neutropenia ≥grade 3, the median time to first occurrence of reactions was 7.07 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). Asciminib (Bacrelba) 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 Asciminib (Bacrelba), with grade 3 reactions occurring in 22 (4%) patients. Among the patients with anaemia ≥grade 3, the median time to first occurrence of reactions was 22.21 weeks (range: 0.14 to 207 weeks) with median duration of any occurring reaction of 0.79 weeks (95% CI, range: 0.29 to 1.71 weeks). Asciminib (Bacrelba) was temporarily withheld in 2 (0.4%) patients due to anaemia.