General Information

Scemblix (asciminib) is a kinase inhibitor.

Scemblix is specifically indicated for:

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). This indication is approved under accelerated approval 
• Ph+ CML in CP with the T315I mutation

Scemblix is supplied as tablets for oral administration. Avoid food for at least 2 hours before and 1 hour after taking Scemblix. Swallow tablets whole. Do not break, crush, or chew the tablets.

• Recommended Dosage in Ph+ CML in CP: 80 mg orally once daily or 40 mg twice daily.
• Recommended Dosage in Ph+ CML in CP with the T315I Mutation: 200 mg orally twice daily.

Mechanism of Action

Scemblix (asciminib) is an ABL/BCR-ABL1 tyrosine kinase inhibitor. Asciminib inhibits the ABL1 kinase activity of the BCRABL1 fusion protein, by binding to the ABL myristoyl pocket. In studies conducted in vitro or in animal models of CML, asciminib showed activity against wild-type BCR-ABL1 and several mutant forms of the kinase, including the T315I mutation.

Side Effects

Adverse effects associated with the use of Scemblix may include, but are not limited to, the following:

• upper respiratory tract infections
• musculoskeletal pain
• fatigue
• nausea
• rash
• diarrhea
• laboratory abnormalities

Clinical Trial Results

Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). This indication is approved under accelerated approval based on major molecular response (MMR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 

Ph+ CML in CP with the T315I mutation

The FDA approval of Scemblix is based on results from the Phase III ASCEMBL trial and a Phase I study that included patients with Ph+ CML-CP with the T315I mutation.

In patients with Ph+ CML-CP who had experienced resistance or intolerance to at least two TKIs, the ASCEMBL trial showed that Scemblix nearly doubled the MMR rate vs. Bosulif (bosutinib) at 24 weeks (25% vs. 13%). The proportion of patients who discontinued treatment due to adverse reactions was more than three times lower in the Scemblix arm (n = 156) vs. patients in the Bosulif arm (n = 76) (7% vs. 25%).

In the phase 1 trial, efficacy was based on 45 patients with Ph+ CML-CP with the T315I mutation who received Scemblix at a dose of 200 mg twice daily. Patients continued treatment until unacceptable toxicity or treatment failure occurred. MMR was achieved by 24 weeks in 42% of the 45 patients treated with Scemblix. MMR was achieved by 96 weeks in 49% of the 45 patients treated with Scemblix. The median duration of treatment was 108 weeks.