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Real-World Evidence is Front-and-Center in Alzheimer’s Disease

Wednesday, June 21, 2023

An estimated 6.7 million Americans aged 65 and older are living with Alzheimer’s dementia1. The total lifetime cost of care of a person with Alzheimer’s disease is approximately $392,874 (in 2022 dollars) including out-of-pocket costs, Medicare, and Medicaid expenditures1.

With no disease-modifying or curative treatments marketed, and a previously published failure rate in Alzheimer’s disease clinical trials of 99.6%2, the development of therapeutics for Alzheimer’s disease seems very risky. Despite these numbers, there is recent enthusiasm that Pharma continues to push for novel therapeutics even with a high barrier to success. The Alzheimer’s Association reported that there were 143 drug candidates in the clinical development pipeline in 2022, 83.2% of which were disease-modifying3. The furthest along in development are three monoclonal antibodies that target amyloid-beta (Aβ) plaques in the brain, a defining feature of Alzheimer’s disease. These therapeutics include Eisai and Biogen’s lecanemab, Eli Lilly’s donanemab, and Genentech’s gantenerumab.

On January 7, 2023, Eisai and Biogen announced that the U.S. Food and Drug Administration (FDA) approved LEQEMBITM (lecanemab) for the treatment of Alzheimer’s disease under the Accelerated Approval Pathway 4. The FDA’s Accelerated Approval program is intended “to allow for earlier approval of drugs that treat serious conditions and fill an unmet medical need5,” allowing sponsors to use a surrogate endpoint that predicts clinical benefit but is not itself a measure of clinical benefit5. In the case of LEQEMBITM, approval was based on a reduction of amyloid plaques. However, to receive traditional FDA approval, sponsors are still required to conduct confirmatory studies that the drug does provide a clinical benefit. A committee of experts who advises the FDA on brain medicines met on June 9, 2023, voting 6-0 that the recently collected confirmatory clinical trial data shows that LEQEMBITM does indeed benefit Alzheimer’s patients6. This vote supports traditional approval, which should be decided by the agency by July 6, 20236.

At the time of approval, the Centers for Medicare and Medicaid Services (CMS) policy required enrollment in a clinical trial as a condition of coverage of antibody treatments that received expedited approval7. This limited LEQEMBITM access to patients who were close enough to clinical trial sites to participate, largely excluding patients living in rural and underserved areas, and wealthy patients who could afford to pay out-of-pocket. On June 1, however, CMS announced that it will cover Alzheimer’s disease drugs that are granted traditional approval7. The stated policy requires the patient to be actively enrolled in Medicare Part B with a diagnosis of mild cognitive impairment or early dementia caused by Alzheimer’s disease. Also, the patient’s physician and clinical team must participate in a registry, where real-world data would be collected about how the drug works7.

Registries are vital approaches to collecting real-world data that inform patient care. Pertaining to the CMS announcement, however, both PhRMA and the Alzheimer’s Association have released statements saying that registries are an unnecessary barrier to care8-9. PhRMA also voiced concerns that patients might be forced to travel to providers participating in the registry program and that the registry might not be available when the FDA approval comes through8.

These concerns create opportunities for manufacturers to engage with partners who have deep experience planning and operationalizing patient-centric registries in the post-approval setting. Identification of evidence gaps through a systematic review of external stakeholder requirements, the current clinical and scientific landscape, and internal strategic initiatives is a good first step. Utilizing existing infrastructure and integrating existing registries are other practical solutions, leveraging efforts already in place, and information already being collected in a real-world setting. Finally, well-designed registries that leverage modernized technology and data acquisition approaches, including decentralized study design, may reduce burden on providers and patients, and help lower certain barriers to care for these patients and/or caregivers or care teams. Having partners well-versed in such study approaches can help reduce the time to plan and operationalize studies by bringing experience and expertise needed to best support study design, operational aspects, recruitment and retention, and the technology and infrastructure needed.

The Alzheimer’s patient community, advocacy groups, regulators, coverage bodies, and manufacturers are on the cusp of a material breakthrough. Having an organization that understands the intersection of these equally important agendas and data requirements to ensure successful outcomes, in concert with the safe and appropriate use of the drug, combined with the need to ensure reasonableness and outcomes of the therapy is a new ground – UBC is ready.

About UBC

United BioSource LLC (UBC) is the leading provider of evidence development solutions with an expertise in unifying evidence and access. UBC helps biopharma mitigate risk, address product hurdles, and demonstrate safety, efficacy, and value under real-world conditions. Bringing over 30 years of experience, UBC is uniquely positioned to develop end-to-end integrated evidence generation strategies, identify fit-for-purpose data sources, operationalize planned studies, and ensure regulatory-grade, publishable outputs.

To find out more about how UBC can help you on your RWE journey, get in touch with our team here.

About the Author

Judith Lytle, PhD, MBEE, PMP, is the Executive Director of Real-World Evidence Study Solutions at UBC. She utilizes her extensive expertise to help biopharma develop evidence generation strategies, powered by rigorous science, that are designed to demonstrate value.



1. Alzheimer’s Association. 2023 Alzheimer’s Disease Facts and Figures. Alzheimer’s Dement 2023;19(4). DOI 10.1002/alz.13016.
2. J.L. Cummings, T. Morstorf, K. Zhong, Alzheimer’s disease drug-development pipeline: few candidates, frequent failures, Alzheimers Res. Ther. 14 (4) (2014). 37.
3. J. Cummings, G. Lee, P. Nahed, et al. Alzheimer’s disease drug development pipeline: 2022. Alzheimer’s Dement. 2022; 8:e12295.
4. Eisai. “FDA Approves LEQEMBI™ (lecanemab-irmb) Under the Accelerated Approval Pathway for the Treatment of Alzheimer’s Disease.” Current as of January 7, 2023. Accessed June 6, 2023.
5. U.S. FDA. “Accelerated approval program.” Current as of May 30, 2023. Accessed June 6, 2023.
6. Biopharma Dive. “FDA panel backs full approval for Esai, Biogen Alzheimer’s drug.” Current as of June 9, 2023. Accessed June 9, 2023.
7. CMS. “CMS announces plan to ensure availability of new Alzheimer’s drugs.” Current as of June 1, 2023. Accessed June 6, 2023.
8. CNBC. “Bipartisan attorneys general call on Medicare to cover Alzheimer’s treatments.” Current as of May 1, 2023. Accessed June 6, 2023.
9. Fierce Pharma. PhRMA cries foul on CMS’ registry approach for Alzheimer’s disease drugs. Current as of June 2, 2023. Accessed June 6, 2023.