FDA Greenlights Novartis’ First-in-Class Therapy for CML

Courtesy of Harold Cunningham/Getty Images

Courtesy of Harold Cunningham/Getty Images

Scemblix is the first-in-class FDA-approved treatment for adult patients diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia.

Harold Cunningham/Getty Images The U.S. Food and Drug Administration (FDA) has approved Novartis’ Scemblix (asciminib) for two indications in the treatment of chronic myeloid leukemia (CML).

Scemblix is the first-in-class FDA-approved treatment in CML that works by binding to the ABL myristoyl pocket. It is indicated for adult patients diagnosed with Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP) who have undergone at least two rounds of treatment using tyrosine kinase inhibitors (TKIs). Further approvals under the Accelerated Approval Program will depend on additional evidence of clinical benefits. In addition, Scemblix is allowed for use in adult patients with the same diagnosis but with a T31RI mutation.

Also referred to as a STAMP inhibitor, Scemblix works by binding to the ABL myristoyl pocket, offering a ray of hope for patients who have been intolerant of current TKI therapies and/or have experienced resistance.

Studies show that around 55% of those who have taken two TKIs experienced intolerance, while as many as 70% are unable to reach major molecular response (MMR) within two years. Those with a T31RI mutation are generally resistant to TKIs, leaving them with no option but to suffer progression. The mutation happens at the defective BCR-ABL1 gene, which is linked to the over-production cells that lead to leukemia.

The FDA’s decision is based on positive results from the Phase III ASCEMBL trial and a Phase I trial on patients with Ph+ CML-CP with T31RI mutation.

During the 24-week study period, Scemblix was able to almost double the molecular response rate (MMR) rate versus the currently used Bosulif (bosutinib), while the percentage of patients who stopped treatment due to adverse reactions was only 7% (versus 25% in Bosulif). Some of the adverse reactions observed under Scemblix are musculoskeletal pain, lowered hemoglobin, platelet, neutrophil counts, upper respiratory tract infections, increased creatine kinase, triglycerides, and alanine aminotransferase (ALT).

“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,” noted Dr. Michael J. Mauro, hematologist and myeloproliferative neoplasms program leader at Memorial Sloan Kettering Cancer Center (MSK), in the same press release.

Scemblix, offered in tablet form, is now available for physicians to prescribe for qualified adult patients in the United States. Those who are qualified to take the drug should inform their physicians of any history of heart problems, pancreatitis, or blood clots. It is not recommended for pregnant women, and those breastfeeding should wait at least a week to resume after taking the drug. It is not yet known whether it is effective and safe in children.

Novartis has reportedly begun filing for regulatory approvals in multiple regions and countries.