The U.S. Food and Drug Administration (FDA) has granted approval to Novartis' Scemblix (asciminib) for two indications in adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). This includes patients who have previously been treated with two or more tyrosine kinase inhibitors (TKIs) and those with the T315I mutation.
Scemblix represents a first-in-class treatment that functions as an ABL myristoyl pocket binder. This novel mechanism of action provides a new therapeutic avenue for patients who have developed resistance or intolerance to currently available TKI therapies. The approval is based on data from the Phase III ASCEMBL trial and a Phase I trial focusing on patients with Ph+ CML-CP harboring the T315I mutation.
Clinical Trial Data
The Phase III ASCEMBL trial demonstrated a significantly higher molecular response rate (MMR) at 24 weeks with Scemblix compared to bosutinib, a commonly used TKI. Specifically, Scemblix nearly doubled the MMR rate, while also exhibiting a more favorable safety profile. The percentage of patients discontinuing treatment due to adverse reactions was notably lower in the Scemblix arm (7%) compared to the bosutinib arm (25%). Adverse reactions observed with Scemblix included musculoskeletal pain, decreased hemoglobin, platelet, and neutrophil counts, upper respiratory tract infections, elevated creatine kinase, triglycerides, and alanine aminotransferase (ALT).
Addressing Unmet Needs in CML Treatment
Approximately 55% of patients treated with two or more TKIs experience intolerance, and up to 70% fail to achieve a major molecular response (MMR) within two years. Patients with the T315I mutation are often resistant to TKIs, leaving them with limited treatment options and a poorer prognosis. Scemblix offers a crucial alternative for these patients, targeting the BCR-ABL1 gene, which drives the overproduction of cells leading to leukemia.
Expert Commentary
Dr. Michael J. Mauro, a hematologist and myeloproliferative neoplasms program leader at Memorial Sloan Kettering Cancer Center (MSK), highlighted the importance of this approval: "CML can be difficult to treat when currently available treatments fail patients, when treatment side effects cannot be tolerated, or sometimes both. The addition of Scemblix into the CML treatment landscape gives us a novel approach to combat this blood cancer, helping address clinical challenges in patients struggling after switching to a second treatment, as well as in patients who develop the T315I mutation and face significantly worse outcomes."
Availability and Usage
Scemblix is available in tablet form for prescription by physicians to qualified adult patients in the United States. Patients should inform their physicians about any history of heart problems, pancreatitis, or blood clots. The drug is not recommended for pregnant women, and breastfeeding should be avoided for at least one week after taking the drug. The safety and efficacy of Scemblix in children have not yet been established.
Novartis has initiated the process of seeking regulatory approvals for Scemblix in various other regions and countries.
