Novartis announced that Scemblix^® (asciminib) was granted accelerated approval by the US Food and Drug Administration (FDA) for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP).

The accelerated approval is based on major molecular response rate (MMR) at week 48 from the ASC4FIRST Phase III trial that compared once daily Scemblix to all other investigator-selected (IS) standard of care (SoC) tyrosine kinase inhibitors (TKIs) (imatinib, nilotinib, dasatinib, and bosutinib). In the study, Scemblix demonstrated superior MMR rates in both primary endpoints at week 48 vs. IS SoC TKIs and imatinib alone^1-3. Continued approval for the newly diagnosed indication may be contingent upon verification and description of clinical benefit from confirmatory evidence.

The expanded indication in Ph+ CML-CP increases the population eligible for Scemblix by approximately four times, including newly diagnosed and previously treated adults. Newly diagnosed patients will now have access to a treatment that has shown superior efficacy vs. all standard of care therapies and a favorable safety and tolerability profile.

“Many patients who are newly diagnosed with CML struggle to navigate this chronic condition and may switch or even stop treatment because of side effects that interrupt their daily lives,” said Lee Greenberger, Ph.D., Chief Scientific Officer at The Leukemia & Lymphoma Society. “That’s why approvals of new first-line treatment options are so important. For patients, finding a medicine that’s right for them at the very beginning of treatment may lead to better long-term disease control with fewer side effects.”

While TKIs have transformed CML into a chronic disease, efficacy and safety challenges continue to hinder long-term treatment success for many patients. Many newly diagnosed patients do not meet molecular response goals, and many discontinue or change treatment due to intolerance^4-23. Nearly half of CML patients do not meet efficacy milestones (MMR) and almost one in four patients discontinue or switch treatment within one year^4-5.

“While there are a range of effective TKIs currently available for newly diagnosed patients, clinicians frequently have had to weigh sacrificing either efficacy or tolerability,” said Jorge Cortes, M.D., Director, Georgia Cancer Center. “In the first-of-its-kind ASC4FIRST trial, Scemblix achieved impressive results across all three parameters of efficacy, safety and tolerability versus all standard of care TKIs. This Scemblix data has the potential to be practice-changing.”

The FDA approval of Scemblix is based on results from the Phase III ASC4FIRST trial in patients newly diagnosed with Ph+ CML-CP. Data showed:

• Nearly 20% more patients treated with Scemblix achieved MMR vs. IS SoC TKIs (imatinib, nilotinib, dasatinib and bosutinib) (68% vs. 49%, < 0.001) and nearly 30% more patients achieved MMR vs. imatinib alone (69% vs. 40%, < 0.001) at week 48^1-2
• Scemblix is the first CML treatment to show superior efficacy along with a favorable safety and tolerability profile vs. imatinib and second generation TKIs, with fewer treatment-related grade ≥3 ARs (25.5% vs. 33% and 42%), dose reductions (6% vs. 14% and 24%), and half the rate of ARs leading to treatment discontinuation (4.5% vs. 11% and 9.8%)^1-3
• Patients treated with Scemblix also achieved deeper rates of molecular responses including MR4 compared with IS-TKIs and imatinib alone (41% vs. 22% and 16%) by week 48^1-2
• In newly diagnosed patients, the safety profile was consistent with previous registration studies with no new safety concerns observed. The most common ARs (≥ 20%) were musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain and diarrhea^1-3

The ASC4FIRST trial remains ongoing, with the next scheduled analysis at week 96 to evaluate the key secondary endpoint (MMR at week 96) and additional secondary endpoints.

The approval was also supported by preliminary data from the Phase II ASC2ESCALATE study, which includes Ph+ CML-CP patients who have been previously treated with one prior TKI with discontinuation due to treatment failure, warning, or intolerance. Data will be shared at a future medical meeting.

“We are proud to help redefine CML treatment once again with Scemblix, as we continue to deliver on our 20+ year commitment to innovation and support in CML,” said Victor Bulto, President US, Novartis. “Despite many advances in the field, patients still need treatment options that are highly effective with a favorable tolerability profile to help enable them to achieve meaningful outcomes as they manage chronic conditions. With this approval, we can offer newly diagnosed adult Ph+ CML-CP patients a new treatment option that combines both, with the potential to change the trajectory of many more people living with CML.”