Novartis' Scemblix (asciminib) has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), recommending its approval for adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) who have been previously treated with two or more tyrosine kinase inhibitors (TKIs). This decision is based on the Phase III ASCEMBL trial results, which demonstrated a significant improvement in major molecular response (MMR) and a lower rate of adverse events compared to bosutinib.
The positive CHMP opinion is based on data from the pivotal Phase III ASCEMBL trial, which evaluated Scemblix versus bosutinib in patients with CML who had failed at least two prior TKIs. The results showed that Scemblix nearly doubled the MMR rate at 24 weeks compared to bosutinib (25.5% vs. 13.2%). Furthermore, the discontinuation rate due to adverse reactions was more than three times lower in the Scemblix arm (5.8%) compared to the bosutinib arm (21.1%).
Clinical Efficacy and Safety
The ASCEMBL trial's longer-term follow-up data, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, reinforced the initial findings. At 96 weeks, the MMR rate in the Scemblix arm was more than double that of the bosutinib arm (37.6% vs. 15.8%, P=.001). The probability of maintaining MMR for at least 72 weeks in patients treated with Scemblix was 96.7% (95% CI, 87.4%–99.2%), indicating durable efficacy.
Despite a longer median duration of exposure in the Scemblix arm (23.7 months) compared to the bosutinib arm (7.0 months), the discontinuation rate due to adverse events remained significantly lower with Scemblix (7.7% vs. 26.3%). Common adverse reactions reported in the Scemblix arm included thrombocytopenia (29.5%) and neutropenia (23.1%).
Novel Mechanism of Action
Scemblix is the first CML treatment that functions as a STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor. This novel mechanism of action allows it to specifically target the ABL myristoyl pocket, potentially overcoming resistance and mutations in the BCR::ABL1 gene, which drives the overproduction of leukemic cells in CML.
Dr. Andreas Hochhaus, Head of the Department of Hematology and Medical Oncology at Jena University Hospital in Germany, noted, "Although CML treatments have advanced over the last 20 years, many patients continue to experience side effects and resistance to treatment, affecting their quality of life and putting them at risk of disease progression or even death. If approved, the novel mechanism of action of Scemblix brings us another option to combat these challenges faced by patients — offering new hope in the management of their disease."
Ongoing Clinical Development
Novartis is continuing to investigate Scemblix across multiple treatment lines for CML-CP, both as a monotherapy and in combination. The ASC4FIRST Phase III study (NCT04971226) is evaluating Scemblix in newly diagnosed adult patients with Ph+ CML-CP compared to an investigator-selected TKI.
The CHMP recommendation will now be reviewed by the European Commission (EC), with a final decision expected in the coming months. Scemblix has already received approval in the United States and other countries for adult patients with Ph+ CML-CP who have experienced resistance or intolerance to at least two prior TKI therapies.
