FDA approves Scemblix, with novel mechanism of action for the treatment of chronic myeloid leukemia.-Novartis

The FDA granted Scemblix accelerated approval for adult patients with Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine kinase inhibitors (TKIs), based on major molecular response (MMR) rate at 24 weeks; and full approval for adult patients with Ph+ CML-CP with the T315I mutation. In accordance with the Accelerated Approval Program, continued approval for the first indication may be contingent upon verification and description of clinical benefit from confirmatory evidence.

Scemblix is the first FDA-approved CML treatment that works by binding to the ABL myristoyl pocket, and represents an important development for patients who experience resistance and/or intolerance to currently available TKI therapies. Also known as a STAMP inhibitor in scientific literature, Scemblix is being studied across multiple treatment lines for CML-CP, including the ASC4FIRST Phase III study evaluating Scemblix as a first-line treatment.

“The introduction of TKIs twenty years ago revolutionized treatment for CML; however, there remain many patients who do not respond adequately to at least two available treatments and often experience challenging side effects that add a burden to their daily lives,” said Lee Greenberger, Chief Scientific Officer at The Leukemia & Lymphoma Society. “The approval of Scemblix may offer hope to patients by addressing gaps in CML care.”

For many patients, current treatment for CML may be limited by intolerance or resistance, and sequential use of available TKIs is associated with increased failure rates. In an analysis of patients with CML treated with two prior TKIs, approximately 55% reported intolerance to previous treatment. Additionally, a pooled analysis in the second-line setting showed that up to 70% of patients are unable to achieve major molecular response (MMR) within two years of follow-up. Moreover, patients who develop the T315I mutation are resistant to most available TKIs, leaving them at an increased risk of disease progression.

“CML can be difficult to treat when currently available treatments fail patients, when treatment side effects cannot be tolerated, or sometimes both,” expressed Dr. Michael J. Mauro , Hematologist and Myeloproliferative Neoplasms Program Leader at Memorial Sloan Kettering Cancer Center (MSK). “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.”

The FDA approval of Scemblix is based on results from the Phase III ASCEMBL trial and a Phase I (NCT02081378) study that included patients with Ph+ CML-CP with the T315I mutation. In patients with Ph+ CML-CP who had experienced resistance or intolerance to at least two TKIs, the ASCEMBL trial showed that:• Scemblix nearly doubled the MMR rate vs. Bosulif (bosutinib) at 24 weeks (25% vs. 13% [P=0.029]).• The proportion of patients who discontinued treatment due to adverse reactions was more than three times lower in the Scemblix arm (n = 156) vs. patients in the Bosulif arm (n = 76) (7% vs. 25%).• The most common (incidence greater than 20%) adverse reactions and laboratory abnormalities in the Scemblix arm were, respectively: upper respiratory tract infections and musculoskeletal pain; decrease in platelet and neutrophil counts, decrease in hemoglobin; increase in triglycerides, creatine kinase and alanine aminotransferase (ALT).

Scemblix is currently available for physicians to prescribe to appropriate patients in the US.

Novartis has initiated regulatory filings for Scemblix in multiple countries and regions across the globe. .