Scemblix hits the front line

It was just over three years ago that the Novartis drug now known as Scemblix made its first splash, in late-line chronic myelogenous leukaemia, and today the Swiss firm has the front-line setting in its sights. The ASC4first trial has read out positively for its primary endpoint, Novartis says, with Scemblix beating investigator’s choice BCR-ABL tyrosine kinase inhibitors on 48-week major molecular response in first-line Philadelphia chromosome-positive CML. Regulatory filings are to follow this year. ASC4first is notable for showing a benefit head-to-head against established drugs comprising the first-generation Novartis agent Gleevec (which Scemblix also beat in a direct comparison), and the second-generation TKIs Tasigna, Sprycel and Bosulif. Two earlier randomised trials found no survival difference for Gleevec versus Tasigna or versus Sprycel. Scemblix itself beat Bosulif in the Ascembl trial that led to its 2021 approval for third-line CML, while another third-generation asset, Takeda’s Iclusig, is notable for having failed in the first-line Epic trial. Unlike the approved BCR-ABL inhibitors Scemblix specifically hits the oncoprotein’s ABL myristoyl pocket, a fact that could combat the build-up of resistance pathways. One caveat is that US patents on many of the established drugs have already expired.

Selected BCR-ABL tyrosine kinase inhibitors for CML

Source: OncologyPipeline & company statements.