Novartis Receives CDSCO Approval for Phase IIIb Trial of Asciminib in Chronic Myeloid Leukemia

• Novartis Healthcare has secured approval from India's CDSCO expert committee to conduct a Phase IIIb roll-over study of asciminib for patients with Philadelphia chromosome-positive chronic myeloid leukemia.
• Asciminib (ABL001) functions as a novel allosteric inhibitor targeting the BCR-ABL1 kinase's myristoyl pocket, distinguishing it from traditional ATP-competitive tyrosine kinase inhibitors used in CML treatment.
• The multi-center, open-label study will assess long-term safety in patients who have completed previous Novartis-sponsored asciminib trials and are deemed to benefit from continued treatment.

India's Subject Expert Committee (SEC) under the Central Drug Standard Control Organisation (CDSCO) has granted approval to Novartis Healthcare to conduct a Phase IIIb clinical trial of asciminib, a novel treatment for Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML).

The approval follows Novartis's presentation of the clinical study protocol CABL001A2001B (Version 03, dated May 17, 2024) at the SEC Oncology meeting held on March 11, 2025. After detailed deliberation, the committee recommended permission for the trial.

Novel Mechanism of Action

Asciminib, also known as ABL001, represents a significant advancement in CML treatment due to its unique mechanism of action. Unlike traditional tyrosine kinase inhibitors (TKIs) that target the ATP-binding site, asciminib is an allosteric inhibitor that specifically binds to the ABL1 myristoyl pocket of the BCR-ABL1 kinase.

This distinctive binding induces an inactive conformation of the kinase, preventing it from signaling and driving cancer cell proliferation. This mechanism makes asciminib particularly valuable for patients who have developed resistance to conventional TKIs or carry specific mutations like T315I.

Study Design and Patient Population

The approved trial is described as "an open-label, multi-center asciminib roll-over study to assess long-term safety in patients who have completed a Novartis-sponsored asciminib study and are judged by the investigator to benefit from continued treatment."

This Phase IIIb study will focus on evaluating the long-term safety profile of asciminib in patients who have previously participated in Novartis-sponsored asciminib trials and shown clinical benefit from the treatment.

Clinical Applications

Asciminib is currently used to treat Ph+ CML in chronic phase, particularly in two key patient populations:

1. As a first-line treatment option for newly diagnosed patients
2. For patients who can no longer benefit from other leukemia medications, especially those who have failed two or more TKI treatments or harbor the T315I mutation

The medication belongs to the kinase inhibitor class and targets the BCR-ABL1 protein, which is often mutated in CML and serves as the primary driver of the disease.

Significance for CML Treatment

CML is a type of cancer affecting white blood cells, characterized by the presence of the Philadelphia chromosome, a genetic abnormality that results in the production of the BCR-ABL1 fusion protein. While existing TKIs have revolutionized CML treatment, resistance remains a significant challenge.

Asciminib's novel mechanism provides an important alternative for patients who have exhausted other treatment options or developed resistance to conventional therapies. The roll-over study will provide valuable data on the long-term safety and efficacy of this innovative approach to CML management.

The CDSCO panel's approval represents an important step forward in expanding treatment options for CML patients in India and potentially contributing to the global understanding of asciminib's long-term safety profile.