▎WuXiEdited by Kant Content Team

Novartis recently announced that the U.S. FDA has granted accelerated approval to Scemblix (asciminib) for the treatment of newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase (Ph+ CML-CP) in adult patients.According to the press release, Scemblix isThe FirstA drug that demonstrated superior efficacy and favorable safety and tolerability profiles compared to all standard of care (SoC) in Phase 3 trials.

This accelerated approval is mainly based on the primary molecular response (MMR) data at Week 48 from the Phase 3 ASC4FIRST clinical trial. The trial compared the efficacy and safety of once-daily Scemblix with all standard-of-care (SoC) tyrosine kinase inhibitors (TKIs, including imatinib, nilotinib, dasatinib, and bosutinib) chosen by investigators in newly diagnosed Ph+ CML-CP patients.The main data of ASC4FIRST shows:

• At Week 48, the number of patients in the Scemblix group who achieved MMRCompared with the SoC TKIs group selected by researchersNearly 20% higher (68% vs. 49%, P<0.001). AndScemblix GroupThe number of patients achieving MMR compared to those receivingImatinib MonotherapyMore patients treatedNearly 30% (69% vs. 40%, P<0.001).

  
  

  

  ▲Summary of Efficacy Results from the ASC4FIRST Trial (Image Source: Reference [2])

  
  

• In terms of safety and tolerability, Scemblix is the first CML treatment regimen that demonstrates superior performance compared to Imatinib and second-generation TKIs. Scemblix has a lower incidence of ≥Grade 3 treatment-related adverse reactions (25.5% vs. 33% and 42%), a reduced rate of dose adjustments (6% vs. 14% and 24%), and the proportion of discontinuations due to adverse reactions is halved (4.5% vs. 11% and 9.8%).

  
  

• At Week 48,Patients in the Scemblix group achieved deeper molecular response (MR4), with rates of 41% vs. 22% and 16% compared to TKIs and imatinib monotherapy, respectively.

• In newly diagnosed patients, the safety profile was consistent with previous registration studies, and no new safety issues were identified. The most common adverse reactions (≥20%) were musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhea.

The ASC4FIRST trial is still ongoing, with the next analysis scheduled for Week 96 to evaluate the key secondary endpoint (MMR at Week 96) and other secondary endpoints.

Scemblix is an allosteric inhibitor targeting ABL1, which inhibits the activity of BCR-ABL1 by binding to the myristoyl pocket of ABL1.Since it binds to a different site on BCR-ABL1 than common TKIs, it may address the issues of TKI resistance and intolerance in the later treatment stages of patients with chronic myeloid leukemia.The U.S. FDA in October 2021ApprovalScemblix Launched in China forTwo different indications for the treatment of chronic myeloid leukemia.This therapyPreviously granted Breakthrough Therapy designation by the FDA.