Novartis Scemblix®, with novel mechanism of action, approved by the European Commission for adult patients with chronic myeloid leukemia

• Approval based on results from pivotal Phase III ASCEMBL trial, in which Scemblix^® (asciminib) nearly doubled the major molecular response rate vs. Bosulif^®* (bosutinib) (25.5% vs. 13.2%) with a more than three times lower discontinuation rate due to adverse reactions (5.8% vs 21.1%) at 24 weeks and confirmed at 96 weeks^1,2 
  
  
• Known in scientific literature as a STAMP inhibitor, Scemblix offers a different therapeutic option to patients with chronic myeloid leukemia (CML) who struggle with intolerance or inadequate response after at least two prior tyrosine kinase inhibitor treatments^1,2
  
  
• Novartis maintains its 20-year commitment to transform the standard of care in CML, hoping to bring Scemblix to more patients around the world, with ongoing regulatory filings and additional trials in other settings underway

Basel, August 29, 2022 — Novartis today announced that the European Commission (EC) has approved Scemblix^® (asciminib) for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP), previously treated with two or more tyrosine kinase inhibitors (TKIs)¹. Scemblix is the first CML treatment in Europe that works by specifically targeting the ABL myristoyl pocket (also known as a STAMP inhibitor in scientific literature), offering a reimagined treatment approach for patients who experience intolerance and/or resistance to currently available TKI therapies^1,2.

“Until now, patients with CML in Europe had oral TKI therapies with the same mechanism of action to turn to, and those experiencing significant side effects or resistance to these treatment options would often cycle between these very similar therapies, with little success in controlling their disease or improving their quality of life,” said Dr. Andreas Hochhaus, Head of the Department of Hematology and Medical Oncology at Jena University Hospital in Germany. “The approval of Scemblix in Europe is a timely milestone that will help many patients find hope for the management of their CML.”

The EC approval for Scemblix follows a positive opinion by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in June, and the previous designation of Scemblix as an orphan drug; and it is applicable to all 27 European Union member states plus Iceland, Norway and Liechtenstein. The approval is based on results from the pivotal Phase III ASCEMBL trial, which showed a near doubling in MMR rate for patients treated with Scemblix vs. Bosulif^®* (bosutinib) (25.5% vs. 13.2%, [P=.029]), with a more than three times lower discontinuation rate due to adverse reactions (5.8% vs. 21.1%), at the 24-week primary endpoint^1,2. These results were confirmed in the 96-week longer-term follow-up where the MMR rate was more than double with Scemblix (37.6%, 95% CI: 29.99-45.65) compared with Bosulif (15.8%, 95% CI: 8.43-25.96) and the discontinuation rate due to adverse reactions was 7.7% for Scemblix and 26.3% for Bosulif. These data were shared as oral presentations during the annual meetings of the American Society for Clinical Oncology (ASCO) and the European Hematology Association (EHA) in June 2022^3,4. Based on all patients exposed to Scemblix in the ASCEMBL study and in the phase I study, the most common (incidence ≥ 20%) adverse reactions in patients receiving asciminib were musculoskeletal pain (37.1%), upper respiratory tract infections (28.1%), thrombocytopenia (27.5%), fatigue (27.2%), headache (24.2%), arthralgia (21.6%), increased pancreatic enzymes (21.3%), abdominal pain (21.3%), diarrhoea (20.5%) and nausea (20.2%)¹.

“Approval of Scemblix from the European Commission is a critical milestone to help bring this novel treatment to patients living with CML in Europe,” said Haseeb Ahmad, President, Europe Innovative Medicines, Novartis. “Building on more than twenty years of innovation in CML, we are excited by the potential to once again transform the standard of care for more patients around the world.”  

It is estimated that, every year, more than 6,300 people will be diagnosed with CML in Europe⁵. While many patients will benefit from available TKI therapies, a significant proportion may experience intolerance or resistance to these treatments^6-13.

About Scemblix^® (asciminib)
Scemblix is the first CML treatment that acts as a STAMP inhibitor, specifically targeting the ABL myristoyl pocket^1,2. This novel mechanism of action may help address resistance in patients with CML previously treated with two or more TKIs and overcome mutations at the defective BCR::ABL1 gene, which is associated with the over-production of leukemic cells^1,2,14-20.  

Scemblix represents an important development for patients who experience resistance and/or intolerance to currently available TKI therapies, and it is being studied across multiple treatment lines for CML-CP, both as a monotherapy and in combination^1,14-28. Specifically, the ASC4FIRST Phase III study (NCT04971226) evaluates Scemblix in newly diagnosed adult patients with Ph+ CML-CP vs. an investigator-selected TKI²².

Novartis has initiated regulatory filings for Scemblix in multiple countries and regions across the globe. In October 2021, the US FDA granted accelerated approval of Scemblix for adult patients with Ph+ CML-CP, previously treated with two or more TKIs based on MMR rate at 24 weeks, and full approval for adult patients with Ph+ CML-CP with the T315I mutation. In accordance with the Accelerated Approval Program, continued approval for the first indication may be contingent upon verification and description of clinical benefit from confirmatory evidence. The longer-term, 96-week efficacy and safety data have been shared with the FDA and are currently under evaluation through a priority review²⁹.

Scemblix has received approval in several countries outside the US, including Japan, Switzerland, and the United Kingdom, for adult patients with Ph+ CML-CP with resistance or intolerance to at least two or more previous therapies.

Disclaimer
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About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

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*Bosulif is a registered trademark of Pfizer

References

1. Scemblix Summary of Product Characteristics, 2022.
2. Rea D, et al. A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After≥ 2 Prior TKIs. Blood. 2021. DOI: 10.1182/blood.2020009984. PMID: 34407542. 
3. Cortes JE, et al. Oral presentation at ASCO 2022; June 3-7, 2022. Chicago IL and virtual. Abstract 7004  
4. Réa D, et al. Oral presentation at EHA 2022; June 9-17, 2022. Vienna Austria and virtual. Abstract S155 
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17. Hughes TP, et al. Expanded Phase 1 Study of ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Reveals Significant and Durable Responses in Patients with CML-Chronic Phase with Failure of Prior TKI Therapy. Poster presented at: ASH Annual Meeting & Exposition; Dec. 5, 2016.
18. Ottmann OG, et al. ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Exhibits Safety and Promising Single- Agent Activity in a Phase I Study of Patients with CML with Failure of Prior TKI Therapy. Blood. 2015;126(23):138.
19. Mauro MJ, et al. Combination of Asciminib Plus Nilotinib (NIL) or Dasatinib (DAS) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Poster presented at: EHA Annual Meeting; June 15, 2019.
20. Cortes JE, et al. Combination Therapy Using Asciminib Plus Imatinib (IMA) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Poster presented at: EHA Annual Meeting; June 15, 2019.
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23. ClinicalTrials.gov. 2020. Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and WithoutT315I Mutation (AIM4CML). [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04666259.
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29. Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.

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