The drug previously received breakthrough therapy designation for newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia that is in chronic phase.
The FDA has granted priority review for asciminib (Scemblix; Novartis) for the treatment of newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that is in chronic phase. The drug previously received breakthrough therapy designation for the treatment and is also being reviewed under the Real-Time Oncology Review program.1
“We welcome the FDA’s decision to grant priority review and breakthrough therapy designations to [asciminib] for newly diagnosed patients [with CML], which underscores the substantial need for additional effective, safe and tolerable treatment options,” said Rodney Gillespie, senior vice president in therapeutic area head of US Oncology at Novartis, in a statement. "The ASC4FIRST data indicate that [asciminib], if approved, has the potential to address a critical gap in CML by offering a highly effective treatment along with a favorable safety and tolerability profile.”1
The designation is based on results from the ASC4FIRST trial (NCT04971226), a phase 3 study that evaluated the drug’s efficacy, tolerability, and safety compared with the investigators-selected tyrosine kinase inhibitors (TKIs)—imatinib (Gleevec; Novartis), nilotinib (Tasigna; Novartis), dasatinib (Sprycel; Bristol Myers Squibb), and bosutinib (Bosulif; Pfizer)—representing the standard of care for the patient population.1
Investigators of the study included individuals aged 18 years or older with a diagnosis within 3 months. Further, individuals needed a documented chronic phase meeting the criteria. They were excluded if they received previous treatment of CML with any other anticancer agents, including chemotherapy and/or biologic agents or stem cell transplant, impaired cardiac function or cardiac repolarized abnormality, severe or uncontrolled concurrent medical disease, major surgery within 4 weeks prior to the study, and a history of acute pancreatitis or chronic liver disease.2
The primary outcome was major molecular response at week 48, with secondary outcomes including major molecular response at 96 weeks, time to discontinuation due to adverse events (AEs), major molecular response at scheduled data collection time points, complete hematological response at all scheduled data collection time points, complete cytogenic response at week 48 and week 96, duration of major molecular response, event free survival, progression free survival, and overall survival.2
A total of 405 patients were enrolled from November 5, 2021, to December 20, 2022. Investigators assigned asciminib to 201 patients and a TKI to 204 patients. Investigators reported that the main reason for discontinuation was unsatisfactory therapeutic effect and adverse events for both groups. For efficacy, the primary end point with major molecular response at week 48 was 67.7% for asciminib and 49% for TKIs. Further, investigators found that asciminib compared with imatinib at 69.3% and 40.2%, respectively; when compared with second-generation TKIS, asciminib had a major molecular response at week 48 of 66% and 57.8% for second-generation TKIs.3
The safety analysis included 401 individuals. Compared with TKIs, asciminib had a favorable safety profile, AEs of grade 3 or higher occurred in 10% or more individuals in any cohort and were hematological in nature, including thrombocytopenia at 13% with asciminib, 6.1% with imatinib, and 13.7% compared with second-generation TKIs, neutropenia at 10%, 17.2%, and 17.6%, respectively, and leukopenia at 2%, 10.1%, and 4.9%, respectively.3
Previously, asciminib was also given priority review and breakthrough therapy designations for the treatment of Ph+ CML in the chronic phase that was previously treated with 2 or more TKIs.1
