This is a paid editorial funded by Sanofi. Pragmatism is simple. Pragmatism is powerful. We are all working toward common goals in healthcare, and pragmatism can be a driver to turn ideas into a reality. When talking about helping those living with cancer, we continuously need to evolve and find better ways of approaching clinical trials. As the oncology treatment landscape continues to advance, the bar to making meaningful improvements versus standard of care continues to be raised. As cancer prognoses improve and we aim to catch and treat it earlier, time to achieve significant overall survival (OS)* is increasing, if ever reached. As a result, in instances where regulatory/reimbursement processes rely on OS, patient access to innovative treatments is delayed or compromised.1 Faced with this, we need to evolve the way we choose and interpret clinical and biological endpoints to accelerate access to potential life-saving treatments and advance health through personalized medicine. > At Sanofi, we strive to modernize the treatment of cancer by working to bring > new therapies for difficult-to-treat cancers” At Sanofi, we strive to modernize the treatment of cancer by working to bring new therapies for difficult-to-treat cancers and that starts with focusing our efforts to make a difference where we can. To that end, we work closely with leading cancer institutions and cooperative groups, as well as biotech companies and public-private initiatives, like the Paris-Saclay Cancer Cluster, to move the needle on oncology R&D. We’ve centered our efforts on select hematologic malignancies and select solid tumors with critical unmet needs, including multiple myeloma (MM), acute myeloid leukemia (AML), certain types of lymphomas, as well as gastrointestinal and lung cancers.   Not all cancers are created equal > Cancer treatment is not a one-size-fits-all approach – and neither are the > endpoints that are crucial to ensure that any treatments are truly beneficial > to patients” Cancer treatment is not a one-size-fits-all approach – and neither are the endpoints that are crucial to ensure that any treatments are truly beneficial to patients. It is vital that we consider the myriad factors – such as cancer type, stage and the individual preferred outcomes for patients – when determining clinical trial endpoints. By using certain oncology-relevant endpoints, there is an opportunity for earlier measurement of medicine efficacy. Practically speaking, this enables shorter clinical trial durations, potentially leading to quicker approval of treatments that may benefit patients.   Minimal residual disease (MRD)** is an example of an endpoint that can provide earlier readouts.2,3 Both Sanofi and the MM community see this as an opportunity to continue to generate data that demonstrate the correlation between certain patient-relevant endpoints, such as MRD, depth of response and longer-term clinical outcomes.4,5,6,7 To see change, we need to be agile and pragmatic There is a need – at a regulatory and heath technology assessment (HTA) level – to define and accelerate the qualification of patient-relevant endpoints beyond OS. This will support research into treatments that do more than prolong survival, as they may enhance quality of life and other important efficacy outcomes that really matter to patients. Access to newer, potentially more effective treatments can be accelerated if the US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) best practice is considered. The FDA ODAC recently decided there is available data to support the use of MRD as an intermediate endpoint for accelerated approval in MM clinical trials, in both newly diagnosed and relapsed/refractory disease settings.8 > “Despite the available body of evidence, the HTA agencies still consider OS > the ‘gold standard’ endpoint in oncology, creating a misalignment with science > and patients’ interests” Despite the available body of evidence, the HTA agencies still consider OS the ‘gold standard’ endpoint in oncology,9 creating a misalignment with science and patients’ interests to get earlier access to treatments. At a national level, assessment frameworks must also evolve and place greater value on quality-of-life benefits that really matter to patients. These are the type of patient-centered policy changes that the Europe’s Beating Cancer Plan should champion in its next phase. To stay relevant, Europe must consider pursuing the development of guidelines from regulatory, clinical and HTA perspectives to enable the use of biological and patient-centered endpoints. We must first standardize and address key uncertainties in aspects such as key methods, frequencies and sensitivity thresholds at which these new endpoints should be measured10 – and that’s not going to happen without a catalyst. It is very clear that Europe has made huge progress and built strong foundations in its fight against cancer. Now is the time to build on it and think more broadly. Considering biological and additional patient-relevant endpoints is crucial, as we look into measuring outcomes beyond OS. MAT-GLB-2407554-v1.0-11/2024 | November 2024 ____________________ Definitions: * OS: Duration of patient survival from the time of treatment initiation. ** MRD: MRD refers to the small number of cancerous cells that may survive in the body after treatment. The number of surviving cells in MRD is too small for traditional tests (like biopsies or blood tests) to detect. So, a positive MRD test result indicates that cancer cells are present in the body – even at a minute level. References: 1. European Federation of Pharmaceutical Industries and Associations, Oncology Platform. September, 2023. White Paper – Improving the understanding, acceptance and use of oncology–relevant endpoints in HTA body / payer decision-making. Accessed on 6 November, 2024: https://www.efpia.eu/media/t2nlhr0k/improving-the-understanding-acceptance-and-use-of-oncology-relevant-endpoints.pdf 2. Anderson KC, Auclair D, Kelloff GJ, et al. The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications. Clin Cancer Res. 2017;23(15):3980-3993. doi:10.1158/1078-0432.CCR-16-2895 3. Avet-Loiseau H, Ludwig H, Landgren O, et al. Minimal Residual Disease Status as a Surrogate Endpoint for Progression-free Survival in Newly Diagnosed Multiple Myeloma Studies: A Meta-analysis. Clin Lymphoma Myeloma Leuk. 2020;20(1):e30-e37. doi:10.1016/j.clml.2019.09.622 4. Perrot A, Lauwers-Cances V, Corre J, et al. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood. 2018;132(23):2456-2464. doi:10.1182/blood-2018-06-858613 5. Landgren O, Prior TJ, Masterson T, et al. EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma. Blood. 2024;144(4):359-367. doi:10.1182/blood.2024024371 6. Meseha M, Hoffman J, Kazandjian D, Landgren O, Diamond B. Minimal Residual Disease-Adapted Therapy in Multiple Myeloma: Current Evidence and Opinions. Curr Oncol Rep. 2024;26(6):679-690. doi:10.1007/s11912-024-01537-2 7. Munshi NC, Avet-Loiseau H, Anderson KC, et al. A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma. Blood Adv. 2020;4(23):5988-5999. doi:10.1182/bloodadvances.2020002827 8. FDA. April 12, 2024. Final Summary Minutes of the Oncologic Drugs Advisory Committee Meeting April 12, 2024. Accessed on 6 November, 2024: https://www.fda.gov/media/180108/download 9. Holstein SA, Suman VJ, McCarthy PL. Should Overall Survival Remain an Endpoint for Multiple Myeloma Trials? Curr Hematol Malig Rep. 2019;14(1):31. doi:10.1007/s11899-019-0495-9 10. Myeloma Patients Europe. January, 2023. Patient and haematologist perspectives on minimal residual disease testing in myeloma. Accessed on 6 November, 2024: https://www.mpeurope.org/wp-content/uploads/2023/01/MRD-in-myeloma-Report.pdf

The world stands at a critical juncture in the fight against Alzheimer’s disease and dementia. With life expectancy rising globally and more people living longer, the number of individuals affected by dementia is expected to increase in the coming years – and by 2050 will affect as many as 139 million adults globally.[i]This looming crisis demands immediate, coordinated action from governments, healthcare systems and society at large. The 2023 G7 Nagasaki health ministers’ meeting reaffirmed the G7’s promise to promote research and development to improve health outcomes through the prevention, risk reduction, early detection, diagnosis and treatment of dementia including potential disease-modifying therapies.[ii] As the G7 health ministers convened in Italy, passing the torch to Canada for 2025, we call for renewed efforts to prioritize Alzheimer’s disease, the leading cause of dementia, as a public health priority. Despite this commitment, health systems across the world remain woefully unprepared to embrace new innovations in diagnosis and treatment, risking that European patients may be left behind the rest of the world in access to new tools and discouraging research that could lead to medical innovation where therapeutic options today are scarce.  The urgency for ensuring access to treatments and diagnosis Alzheimer’s disease is a devastating and fatal condition that robs individuals of their memories, independence and, ultimately, their futures. [iii] It is estimated that Alzheimer’s disease specifically impacts 416 million people worldwide, or more than one in five people aged 50 and above.[iv] In Europe alone, 7 million people are currently living with the disease, a number that could double by 2030.³ The wider impacts on health systems and economies are also profound – an estimated $2.8 trillion per year, a sum which is predicted to rise to $4.7 trillion by 2030.[v] > Alzheimer’s disease is a devastating and fatal condition that robs individuals > of their memories, independence and, ultimately, their futures. For far too long, a lack of new breakthroughs and a string of clinical trial failures has created helplessness and apathy to the treatment of Alzheimer’s disease, leading to many – including healthcare professionals – thinking it is part of aging and there is nothing we can do. Still today, most cases of Alzheimer’s disease are misdiagnosed, diagnosed too late for treatment to be considered or never diagnosed at all.[iv] With newly investigated treatments that target the underlying pathology of the disease, we are potentially altering and slowing the course of disease progression and delaying the need for care services. Furthermore, advanced testing methods, such as blood-based biomarker tests, are potential game-changers in rapid and accurate diagnosis. > With newly investigated treatments that target the underlying pathology of the > disease, we are potentially altering and slowing the course of disease > progression A decade of remarkable progress The 2013 G8 Dementia Summit in London challenged the Alzheimer’s disease research community to develop a disease-modifying therapy by 2025.[vi] Today, there is not just one, but multiple therapies in the field that have been demonstrated to deliver meaningful benefits. We know that the hallmarks of the disease can appear two decades before symptoms manifest.[vii] We now possess the tools to respond to Alzheimer’s disease informed by patients’ genetic profiles. But only if the disease is detected early enough. Just as detecting cancer cells early and personalized medicine is a winning strategy, we are entering a new stage for Alzheimer’s disease response and management. > We now possess the tools to respond to Alzheimer’s disease informed by > patients’ genetic profiles. But only if the disease is detected early enough People around the world want and deserve access[viii] to diagnosis and treatment options available now, and we must ensure European patients are not left behind. Committing to a future where memories endure We have a historic opportunity to elevate the G7 target for a new era in the fight against dementia and Alzheimer’s disease, drawing on the latest scientific understanding, advanced detection and treatment tools for a potentially far stronger response. Lilly has driven scientific progress for over 35 years, and we have no plans to slow our efforts now. We envision a future where timely detection, accurate diagnosis, appropriate treatment and prevention become reality. We are committed to collaborating with healthcare ecosystems to build the infrastructure needed to scale and adopt scientific advances. Together, we can change the discourse around Alzheimer’s disease and usher in a new era – one of support, understanding and hope.   -------------------------------------------------------------------------------- [i] Alzheimer’s Disease International. Dementia Statistics. Available at: https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/ [ii] G7 Nagasaki Health Ministers’ Communiqué https://www.mhlw.go.jp/content/10500000/001096403.pdf [iii] EBC and EFPIA. (2023). RETHINKING Alzheimer’s disease: Detection and diagnosis. Available at: https://www.braincouncil.eu/wp-content/uploads/2023/04/RETHINK-AlzheimerDisease-Report_DEF3_HD_rvb_03042023.pdf [iv] Alzheimer’s Association (2022) Global estimates on the number of persons across the Alzheimer’s disease continuum. Available at: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12694 [v] Nandi A, Counts N, Chen S, et al. Global and regional projections of the economic burden of Alzheimer’s disease and related dementias from 2019 to 2050: A value of statistical life approach. EClinicalMedicine. 2022;51:101580. Published 2022 Jul 22. doi:10.1016/j.eclinm.2022.101580. [vi] GOV.UK. (n.d.). G8 dementia summit communique. [online] Available at: https://www.gov.uk/government/publications/g8-dementia-summit-agreements/g8-dementia-summit-communique. [vii] Aisen PS, Cummings J, Clifford RJ, On the path to 2025: understanding the Alzheimer’s disease continuum. Alzs Res Therapy. 2017 9: 60. [viii] World Alzheimer Report 2024 | Alzheimer’s Disease International (ADI) (alzint.org)