FDA Approves Novartis Scemblix® for New CML Cases with Superior Efficacy and Safety

Novartis has recently announced that the US Food and Drug Administration (FDA) has granted accelerated approval for Scemblix® (asciminib) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). This approval is a significant step forward for patients, as the treatment demonstrated superior major molecular response (MMR) rates in comparison to all other standard of care (SoC) tyrosine kinase inhibitors (TKIs) in the ASC4FIRST Phase III trial.

The trial results showed that Scemblix had superior efficacy compared to investigator-selected SoC TKIs, including imatinib, nilotinib, dasatinib, and bosutinib. At week 48, nearly 20% more patients treated with Scemblix achieved MMR compared to those on SoC TKIs (68% vs. 49%), and approximately 30% more patients achieved MMR compared to those on imatinib alone (69% vs. 40%). Additionally, Scemblix patients experienced fewer treatment-related adverse reactions (ARs) leading to discontinuation, with half the rate compared to SoC TKIs.

Scemblix's approval now covers both newly diagnosed and previously treated adults with Ph+ CML-CP, significantly expanding the pool of eligible patients. This broader indication is expected to provide many more patients access to a treatment option that has shown to be more effective and better tolerated than current SoC therapies.

Dr. Lee Greenberger, Chief Scientific Officer at The Leukemia & Lymphoma Society, emphasized the importance of new first-line treatment options for patients, highlighting that many newly diagnosed CML patients struggle with side effects from existing treatments. These adverse effects often lead to treatment discontinuation or switching. The approval of Scemblix offers a new option that can potentially provide better long-term disease control with fewer side effects.

Currently available TKIs have transformed CML into a manageable chronic condition, but challenges in long-term treatment success persist. Many patients do not achieve molecular response goals, and a significant number discontinue or switch treatments due to intolerance. Dr. Jorge Cortes, Director of the Georgia Cancer Center, noted that the ASC4FIRST trial showcased Scemblix's impressive results in efficacy, safety, and tolerability compared to all standard TKIs.

The accelerated approval of Scemblix for newly diagnosed patients is based on the MMR rates observed at week 48 in the ASC4FIRST trial. Continued approval may rely on further verification of clinical benefits through confirmatory trials. The ongoing ASC4FIRST trial will continue to evaluate key secondary endpoints, including MMR at week 96 and various safety and efficacy measures.

Scemblix has also been granted Breakthrough Therapy designation by the FDA for its potential to treat newly diagnosed adult patients with Ph+ CML-CP. It works by specifically targeting the ABL myristoyl pocket, a mechanism distinct from other TKIs, which target the ATP-binding site. Scemblix is already approved in over 75 countries, including the European Union, for treating patients previously treated with two or more TKIs.

Novartis has a longstanding commitment to innovation in CML treatment, with over 20 years of research and support efforts. The company continues to focus on addressing unmet patient needs and overcoming barriers to access and affordability. With the approval of Scemblix, Novartis aims to provide a new treatment option that combines high efficacy with favorable tolerability, potentially improving outcomes for many more patients with CML.

In summary, the FDA's approval of Scemblix marks a milestone in CML treatment, offering a promising new first-line therapy for newly diagnosed patients. The drug's superior efficacy and tolerability profile could significantly impact clinical practices and patient outcomes, affirming Novartis' dedication to advancing CML care.