Novartis Announces Compelling Long-Term Results for Scemblix® in Phase III ASC4FIRST Trial, Highlighting Superiority in Treating Chronic Myeloid Leukemia

Novartis Announces Compelling Long-Term Results for Scemblix® in Phase III ASC4FIRST Trial, Highlighting Superiority in Treating Chronic Myeloid Leukemia

(IN BRIEF) Novartis has announced promising 96-week results from the Phase III ASC4FIRST trial, showcasing Scemblix® (asciminib) as a superior treatment for newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase (Ph+ CML-CP). Scemblix achieved significantly higher major molecular response (MMR) rates compared to standard-of-care TKIs (74.1% vs. 52%) and imatinib alone (76.2% vs. 47.1%), along with a favorable safety and tolerability profile, including fewer severe adverse events and a lower discontinuation rate. These findings, presented at the 66th ASH Annual Meeting, reinforce Scemblix as a preferred treatment option, now recommended by the NCCN for first-line use. Novartis also shared interim Phase II ASC2ESCALATE trial data, further highlighting Scemblix’s efficacy in second-line and newly diagnosed settings, solidifying its role in addressing unmet needs in CML care.

(PRESS RELEASE) BASEL, 9-Dec-2024 — /EuropaWire/ —  Novartis (SWX: NOVN), a Swiss multinational pharmaceutical company, has shared promising 96-week findings from its pivotal Phase III ASC4FIRST trial, underscoring the superior efficacy of Scemblix® (asciminib) in achieving major molecular response (MMR) in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase (Ph+ CML-CP). The study evaluated Scemblix against investigator-selected standard-of-care tyrosine kinase inhibitors (TKIs) and imatinib alone, meeting key secondary endpoints with notable outcomes. The data, presented at the 66th American Society of Hematology Annual Meeting, affirm Scemblix’s growing role as a transformative treatment option.

At 96 weeks, Scemblix demonstrated higher MMR rates—74.1% versus 52% compared to all investigator-selected TKIs and 76.2% versus 47.1% against imatinib alone. Additionally, Scemblix outperformed second-generation (2G) TKIs, achieving a 15.1% greater MMR rate (72% versus 56.9%). These results reflect deeper and more durable molecular responses, including higher rates of MR4 and MR4.5, reinforcing Scemblix as a leading therapeutic option for patients.

“This long-term data highlights Scemblix’s capacity to balance efficacy with a favorable safety profile, which is crucial for helping newly diagnosed CML patients achieve sustained treatment milestones,” stated Dr. Jorge Cortes, Director of the Georgia Cancer Center.

The trial also confirmed Scemblix’s tolerability, with fewer grade ≥3 adverse events (AEs) and a significantly lower discontinuation rate due to AEs than comparator treatments. Over 50% fewer patients discontinued Scemblix compared to imatinib and 2G TKIs, showcasing its safety advantage. Commonly reported side effects included diarrhea, headache, and musculoskeletal pain, all manageable within the treatment framework.

In line with these findings, Scemblix continues to gain recognition as a key treatment for both newly diagnosed and previously treated Ph+ CML-CP patients. The therapy has received an expanded indication in the U.S. and is endorsed by the National Comprehensive Cancer Network (NCCN) as a preferred first-line treatment across risk groups.

Novartis also unveiled interim data from the Phase II ASC2ESCALATE trial, which explores Scemblix’s potential in second-line and newly diagnosed settings. Preliminary findings at 24 weeks demonstrated encouraging MMR and deeper molecular responses, alongside a consistent safety profile, further bolstering Scemblix’s versatility.

Jeff Legos, Executive Vice President and Global Head of Oncology Development at Novartis, commented, “These results reflect more than a decade of dedicated research in chronic myeloid leukemia and reaffirm Scemblix’s differentiated profile. We remain committed to addressing unmet needs and delivering innovative solutions for patients worldwide.”

With Scemblix now approved in over 75 countries, including recent U.S. and EU approvals for newly diagnosed and previously treated patients, Novartis continues its long-standing mission to improve outcomes in CML. This commitment is amplified through global partnerships aimed at expanding access to innovative treatments for patients in underserved regions.

About the ASC4FIRST Phase III Clinical Trial
ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix^® 80 mg QD vs. IS first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP^2,6. The trial met both primary endpoints with Scemblix demonstrating superior MMR rates at week 48 vs. investigator-selected SoC TKIs (imatinib, nilotinib, dasatinib and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%) as well as the secondary, non-powered endpoint for the 2G TKI stratum of (66% vs 57.8%)^1,6. The study remains ongoing with further efficacy and safety readouts planned.

About the ASC2ESCALATE Phase II Study
ASC2ESCALATE (NCT05384587) is a Phase II, multicenter, single-arm, dose-escalation study of oral Scemblix^® 80 mg QD in both the second line (2L) and newly diagnosed (1L) Ph+ CML-CP settings in the US ^5,7. While Scemblix is already approved across lines of therapy, this is the first prospective trial to assess asciminib in the 2L setting and a dose-escalation strategy of asciminib as 2L and 1L treatment for patients with CML-CP not meeting molecular milestones ⁵. The proportion of patients achieving MMR at 12 months in the 2L setting will be measured as the primary endpoint ⁵. The study remains ongoing and has completed enrollment with 196 patients (100 patients in 2L, 96 patients in 1L)⁵.

About Scemblix^® (asciminib)
Scemblix^® is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)^4,8,9. Other currently approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive)⁹.

In the US, Scemblix was granted accelerated approval to treat newly diagnosed adults with Ph+ CML-CP and is also approved for previously treated adult patients with Ph+ CML-CP. Outside the US, it is approved in more than 75 countries, including the EU, to treat those who have previously been treated with two or more TKIs with Ph+ CML-CP^2,10,11. In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation^2,3,10.

Scemblix is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination^{2,4,6,8,10,12-24}.

Patient Access and Support
Novartis, with its 20+ year history in CML, is committed to continuing to address areas of unmet patient need and reducing barriers to patient access and affordability that prevent patients from benefiting from innovation. Novartis Patient Support is available to help guide eligible patients through the various aspects of getting started on treatment including help understanding insurance coverage and identifying potential financial assistance options. Patients or providers can call 866-433-8000 or visit support.scemblix.com to learn more.

About Novartis Commitment to CML
Novartis has a long-standing scientific commitment to patients living with CML. For more than two decades, our bold science has helped transform CML from a life-limiting condition for many patients. Despite these advancements, there’s still work to be done. We continue to research ways to target the disease more selectively and to address the challenges of not reaching treatment efficacy goals, experiencing treatment resistance and/or intolerance that many patients face. Our legacy inspires our future innovation – we continue to lead the way in developing novel medicines to address serious unmet needs in CML. Our commitment also goes beyond science. Our 20+ year collaboration with the Max Foundation has provided access to Gleevec (imatinib), Tasigna (nilotinib) and now Scemblix and is delivering tremendous patient impact in low- and middle-income countries, with over 100,000 patients supported to date.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “may,” “committed,” “contingent,” “lead,” “continue,” “ongoing,” “to deliver,” “allowing,” “continuing,” “commitment,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Scemblix, or regarding potential future revenues from Scemblix. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Scemblix will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Scemblix will be commercially successful in the future. In particular, our expectations regarding Scemblix could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide.

Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.

References

1. Cortes JE, Hochhaus A, Hughes TP, et al. Asciminib Continues to Provide Superior Efficacy and Favorable Safety and Tolerability vs Tyrosine Kinase Inhibitors In Newly Diagnosed Chronic Myeloid Leukemia in ASC4FIRST: Week 96 Update. Presented at: 66th ASH Annual Meeting & Exposition; December 7 – 10, 2024; San Diego, CA.
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