Anti-Amyloid Monoclonal Antibody Drugs Continue to Show Promise Treating Alzheimer Disease

Alzheimer disease, a progressive neurological disorder characterized by memory loss and cognitive decline, has long posed a significant challenge to the medical community. However, recent advancements in the field have brought forth new hope in the form of anti-amyloid monoclonal antibody drugs. These novel therapies, including lecanemab (Leqembi) and donanemab, have shown promise in targeting the accumulation of amyloid beta plaques, a hallmark feature of Alzheimer disease.¹

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FDA and CMS

In a significant development, the FDA recently converted lecanemab from accelerated approval to traditional approval for the treatment of mild Alzheimer disease. This marks a milestone as lecanemab becomes the first amyloid beta-directed antibody to receive such recognition.

Lecanemab demonstrated its efficacy with a mean difference of −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001 compared to placebo through the Clinical Dementia Rating Sum of Boxes (CDR-SB) scale, a clinical end point. This sets it apart from its predecessor, aducanumab, which relied on a surrogate end point for its approval in 2021.

Alzheimer disease affects millions of people worldwide and is projected to grow in prevalence. With limited treatment options available, the introduction of anti-amyloid monoclonal antibody drugs brings renewed optimism. These drugs, including lecanemab, target amyloid beta plaques and aim to slow the progression of the disease, providing a potential breakthrough in Alzheimer treatment.²

On April 7, 2022, the Centers for Medicare and Medicaid Services (CMS) issued a National Coverage Determination (NCD) that covers monoclonal antibodies targeting amyloid plaques for the treatment of Alzheimer disease. This decision highlights the growing recognition of the importance of these innovative therapies and potential impact on patient outcomes. As of July 6, 2023, Medicare has declared its coverage of lecanemab under this NCD, ensuring that prescribers and eligible patients have access to this treatment option.³

Affordability

The affordability and accessibility of lecanemab and similar drugs will undoubtedly play a crucial role in their practicality and widespread adoption. The high price tag of these medications has raised concerns about their feasibility for patients and health care systems.

Under Medicare coverage, patients will be responsible for paying the standard 20% coinsurance of the Medicare-approved amount for lecanemab, once they meet the Part B deductible. Although this coverage decision is impactful and a step toward improved accessibility, the cost remains a potential barrier for some individuals seeking treatment.

It is essential to continue exploring strategies to address the affordability aspect of novel therapies, ensuring that they are accessible to more patients. Looking at the specific cost of lecanemab, it is available in 2 formulations: 200 mg/2 mL and 500 mg/5 mL, priced at $152.89 per mL and $152.88 per mL, respectively.

Lecanemab is dosed at 10 mg/kg every 2 weeks. These costs emphasize the financial burden, reinforcing the need for further efforts to make them more affordable.⁴

Looking to the Future

Even with this in mind, the future of Alzheimer research is filled with promise as ongoing studies and clinical trials continue to shed light on the efficacy, safety, and long-term benefits of anti-amyloid monoclonal antibody drugs. These innovative therapies hold great potential to revolutionize the treatment landscape for this debilitating disease.

Several noteworthy studies are currently underway, contributing to the growing body of knowledge in this field. Eisai is conducting a double-blind, placebo-controlled trial (CLARITY AD) that is an extension of a previously published 18-month trial that will conclude in 2027. This study aims to confirm the safety and efficacy of lecanemab in subjects with early Alzheimer disease, providing valuable insights into the potential of this drug.⁵

Biogen's adacadumab, another anti-amyloid monoclonal antibody, is undergoing a phase 3b/4 multicenter study. This randomized, double-blind, placebo-controlled trial is specifically designed to verify the clinical benefit of aducanumab. With an estimated completion date in 2026, this study will offer crucial data on the efficacy and impact of aducanumab in Alzheimer treatment.⁶

Eli Lilly's TRAILBLAZER ALZ trials, consisting of TRAILBLAZER ALZ 2, 3, 4, and 6, are dedicated to exploring the use of donanemab. These trials focus on prevention and clinical efficacy in early Alzheimer disease. With completion dates scheduled between 2024 and 2027, these studies will provide vital insights into the potential of donanemab as a therapeutic option.^7-10

Conclusion

Although the initial results have been encouraging, it remains to be seen how practical the place of these novel therapies in therapy will be considering the high cost associated with them. Affordability and accessibility will play a crucial role in determining the adoption of lecanemab and similar drugs in the future.

Nevertheless, the ongoing research and clinical trials surrounding anti-amyloid monoclonal antibody drugs are expected to provide valuable insights and generate more data on their safety profiles and long-term benefits. It will be intriguing to witness how these drugs perform in real-world applications, shedding light on their true efficacy and impact on patients' lives.

About the Author

Olatunji Gbadebo is a fourth-year pharmacy student attending the University of Hawaii at Hilo Daniel K. Inouye College of Pharmacy.

References

1. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023 Jan 5;388(1):9-21. doi: 10.1056/NEJMoa2212948. Epub 2022 Nov 29. PMID: 36449413.
2. Selkoe DJ. The origins of Alzheimer disease: a is for amyloid. JAMA 2000;283:1615-1617.
3. Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer’s Disease CED Study Registry. CMS. Updated July 6, 2023. Accessed July 13, 2023. CED (cms.gov)
4. Lecanemab. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed July 13, 2023. http://online.lexi.com
5. A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With an Open-Label Extension Phase to Confirm Safety and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease (CLARITY AD). Clinicaltrials.gov identifier: NCT03887455. Updated June 12, 2023. Accessed July 13, 2023. https://www.clinicaltrials.gov/study/NCT03887455
6. A Phase 3b/4 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Verify the Clinical Benefit of Aducanumab (BIIB037) in Participants With Alzheimer's Disease (ENVISION). Clinicaltrials.gov identifier: NCT05310071. Updated June 26, 2023. Accessed July 13, 2023. https://www.clinicaltrials.gov/study/NCT05310071
7. Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease (TRAILBLAZER ALZ 2). Clinicaltrials.gov identifier: NCT04437511. Updated July 12, 2023. Accessed July 13, 2023. https://www.clinicaltrials.gov/study/NCT04437511
8. A Study of Donanemab Versus Placebo in Participants at Risk for Cognitive and Functional Decline of Alzheimer's Disease (TRAILBLAZER ALZ 3). Clinicaltrials.gov identifier: NCT05026866. Updated July 10, 2023. Accessed July 13, 2023. https://www.clinicaltrials.gov/study/NCT05026866
9. A Phase 3, Open-Label, Parallel-Group, 2-Arm Study to Investigate Amyloid Plaque Clearance With Donanemab Compared With Aducanumab-avwa in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER ALZ 4). Clinicaltrials.gov identifier: NCT05108922. Updated January 19, 2023. Accessed July 13, 2023. https://www.clinicaltrials.gov/study/NCT05108922
10. Investigating the Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults With Early Symptomatic Alzheimer's Disease (TRAILBLAZER ALZ 6). Clinicaltrials.gov identifier: NCT05738486. Updated July 12, 2023. Accessed July 13, 2023. https://www.clinicaltrials.gov/study/NCT05738486