FDA Approves Scemblix (asciminib) for Newly Diagnosed Chronic Myeloid Leukemia
Key Insights
The FDA granted accelerated approval to Scemblix (asciminib) for adults with newly diagnosed Philadelphia chromosome (search)-positive chronic myeloid leukemia (search) (CML) in the chronic phase.
The approval was based on the ASC4FIRST trial, which demonstrated a significantly higher major molecular response rate at 48 weeks with Scemblix compared to other tyrosine kinase inhibitors.
In the ASC4FIRST trial, the major molecular response rate at 48 weeks was 68% in the Scemblix arm versus 49% in the tyrosine kinase inhibitor arm.
The FDA has granted accelerated approval to Scemblix (asciminib) for the treatment of adult patients with newly diagnosed Philadelphia chromosome (search)-positive chronic myeloid leukemia (search) (CML) in the chronic phase. This decision marks a significant advancement in the treatment landscape for CML, offering a new first-line option for patients. The approval is based on data from the ASC4FIRST trial, which demonstrated superior efficacy of Scemblix compared to other tyrosine kinase inhibitors (TKIs).
ASC4FIRST Trial Results
The ASC4FIRST trial, a randomized controlled study, included 405 patients with newly diagnosed Philadelphia chromosome (search)-positive CML in the chronic phase. Patients were randomized to receive either Scemblix or an investigator-selected TKI, which included nilotinib (Tasigna), imatinib (Gleevec), bosutinib (Bosulif), or dasatinib. The primary endpoint was the major molecular response (MMR) rate at 48 weeks.
The results showed a statistically significant improvement in MMR at 48 weeks with Scemblix. The MMR rate was 68% in the Scemblix arm compared to 49% in the TKI arm, representing a difference of 19%. Notably, when compared specifically to imatinib (Gleevec), the MMR rate was 69% in the Scemblix arm versus 40% in the imatinib arm, a difference of 30%.
Dr. Jorge E. Cortes, director of the Georgia Cancer Center at Augusta University, who presented the findings at the 2024 American Society of Clinical Oncology Annual Meeting, stated that Scemblix has the potential to change the treatment paradigm in CML. "This is the first study to compare a new drug, in this case [Scemblix], with any of the [tyrosine kinase inhibitors] that are approved in the frontline setting of chronic phase [chronic myeloid leukemia (search)],” Cortes said. “We demonstrated a statistically superior response in terms of [major molecular response] at 48 weeks, both against [Gleevec] and against all [tyrosine kinase inhibitors], and a safety and tolerability profile that favors [Scemblix] against all of the [tyrosine kinase inhibitors], suggesting that this strong benefit-risk profile may change the treatment paradigm in [chronic myeloid leukemia].”
Safety and Tolerability
In assessing the incidence of side effects in patients with newly diagnosed and previously treated Philadelphia chromosome (search)-positive chronic myeloid leukemia (search) in chronic phase, the most common adverse reactions (occurring in at least 20% of patients) were rash, musculoskeletal pain, upper respiratory tract infection, fatigue, abdominal pain, headache, and diarrhea. Common laboratory abnormalities (occurring in at least 40% of patients) included decreased leukocyte count, decreased lymphocyte count, decreased neutrophil count, decreased platelet count, and decreased calcium corrected.
Dosage and Administration
The recommended dose of Scemblix is 80 mg taken orally once daily, or 40 mg taken orally twice daily at approximately 12-hour intervals.
Previous Approvals
Scemblix was previously approved in October 2021 for the treatment of patients with Philadelphia chromosome (search)-positive CML in the chronic phase who have experienced intolerance or inadequate response to two or more TKIs.