The ability to think clearly and make decisions plays a central role in the overall well-being and quality of life in elderly individuals. Many medical conditions and traumas can cause dementia affecting memory, thinking, and the ability to perform daily activities. Dementia is one of the most feared geriatric conditions.1
Alzheimer’s disease (AD) is the most common form of dementia that may contribute to 60-70% of the overall cases. It is characterized by the abnormal accumulation of proteins, such as amyloid plaques and tau tangles within the brain years before the onset of symptoms. As Alzheimer’s progresses, there is the deterioration of brain cells, a decline in neurotransmitters like acetylcholine, and eventual brain atrophy, particularly in memory-related regions. While age is the biggest risk factor, Alzheimer’s can also affect individuals younger than 65 referred to as early-onset Alzheimer’s. Emerging therapies like Lecanemab, lower beta-amyloid in the brain and significantly reduce a decline in cognitive and functional abilities in those diagnosed with early Alzheimer’s.2-3
Current treatment options and unmet needs.
FDA-approved medications such donepezil, rivastigmine, galanthamine, and acetylcholinesterase inhibitors, can help control mild symptoms. However, these pharmacological agents cannot slow or reverse the disease progression because they do not treat the underlying cause of AD or halt the rate of decline.4-5
Over the years, the accuracy of diagnosing Alzheimer's disease has improved significantly due to molecular imaging techniques like tau PET, amyloid PET, or 18F-FDG PET but there is still a dearth of disease-modifying agents that can treat AD.6 The scientific fraternity is heavily invested in finding new molecules, especially disease-modifying therapies. Recent data with Lecanemab re-energized the amyloid theory and concern in monoclonal antibodies against amyloid β.7
Lecanemab -The game changer in treating AD.
Lecanemab/Leqembi™ (BAN 2401), an anti-amyloid β drug from Eisai and Biogen is the first beta-amyloid-targeting drug to pass a full FDA review. The FDA approved the drug on January 6, 2023, for Alzheimer’s disease treatment. The ethical clearance was granted following the results of a phase II clinical study and the results of a phase III trial published in November 2022.8 Lecanemab is a monoclonal antibody composed of a humanized version of the mouse antibody mAb158, which specifically targets protofibrils. It belongs to the IgG1 class of antibodies.9
Lecanemab removes beta-amyloid, a protein that accumulates in the brains of patients with Alzheimer's disease. Pharmaceutical companies sought to develop drugs to target amyloid for two decades, on the theory that removing the protein clumps from the brain could slow or stop memory and thinking problems. The clinical study showed people who received the drug as an infusion every two weeks experienced a 27% decline than those in the placebo group. This was the first Aβ immunotherapy trial to show a substantial slowing of progression on the clinical dementia rating scale-sum of boxes at 18 months in the entire cohort.10
Clinical Evidence
Lecanemab's efficacy was assessed using the findings of Study 301 (CLARITY AD), a Phase III randomized, controlled clinical study. The Phase III study included 1,795 individuals with AD in a multicentre, randomized, double-blind, placebo-controlled, parallel-group research. The therapy was started in patients experiencing moderate cognitive impairment or mild dementia with amyloid beta pathology evaluated. Patients were randomly allocated to receive either placebo or Lecanemab at a dosage of 10 milligrams (mg)/kilogram (kg) every two weeks in a ratio of 1:1.11
When compared with the placebo, lecanemab revealed a statistically significant and clinically noteworthy reduction in declining from baseline to 18 months on the primary endpoint, the Clinical Dementia Rating Scale Sum of Boxes score. All secondary endpoints, including the Alzheimer's Disease Assessment Scale Cognitive Subscale 14 and the Alzheimer's Disease Cooperative Study-Activities of Daily Living, revealed statistically significant changes between treatment groups.11
Lecanemab is the first amyloid beta-directed antibody approved for the treatment of Alzheimer's disease. The drug works by lowering amyloid plaques that accumulate in the brain, which represent a distinguishing pathophysiological aspect of the disease. Monoclonal antibodies are redefining drugs and creating a new terrain for therapeutic research thus giving new hope for early Alzheimer’s disease.
Indications and Usage: Treatment with Lecanemab should be started in individuals with moderate memory loss or mild dementia.
Dosage Formulations and Strengths:8
Injection:
- Single-dose vial contains 500 mg/5 mL (100 mg/mL) solution.
- Single-dose vial contains 200 mg/2 mL (100 mg/mL) solution.
About the Author: Silpa Rani Gajavalli, is a pharmacy post graduate, passionate for medical research and medical writing. She is keen to understand pharmacological agents, innovative treatment options, scientific discoveries and regulatory principles. Click her to connect with Silpa Rani.
References
1. Langa KM. Cognitive Aging, Dementia, and the Future of an Aging Population. In: National Academies of Sciences, Engineering, and Medicine; Division of Behavioral and Social Sciences and Education; Committee on Population; Majmundar MK, Hayward MD, editors. Future Directions for the Demography of Aging: Proceedings of a Workshop. Washington (DC): National Academies Press (US); 2018 Jun 26.
2. Dementia. Available at: https://www.who.int/news-room/fact-sheets/detail/dementia/?gclid=CjwKCAjwvfmoBhAwEiwAG2tqzBHEwtMhF9KYiiKybaTEigr39LydD2xs_ub8Gy-QKp66qaOX7QvZSxoCB8cQAvD_BwE Accessed on 5th October 2023.
3. Causes. Alzheimer’s disease. Available at: https://www.nhs.uk/conditions/alzheimers-disease/causes/#:~:text=Alzheimer's%20disease%20is%20thought%20to,form%20tangles%20within%2 0brain%20cells. Accessed on 5th October 2023.
4. Lecanemab Approved for Treatment of Early Alzheimer’s Disease. Available at: https://www.alz.org/alzheimers-dementia/treatments/lecanemab-leqembi Accessed on 5th October 2023.
5. Qiao Y, Chi Y, Zhang Q, et al. Safety and efficacy of lecanemab for Alzheimer’s disease: a systematic review and meta-analysis of randomized clinical trials. Front. Aging Neurosci. 2023; 15:1169499.
6. Ayaz M, Junaid M, Ullah F, et al. Comparative chemical profiling, cholinesterase inhibitions and anti-radicals properties of essential oils from Polygonum hydropiper L: a preliminary anti- Alzheimer's study. Lipids Health Dis. 2015 Nov 4;14:141.
7. Cummings J. Anti-Amyloid Monoclonal Antibodies are Transformative Treatments that Redefine Alzheimer's disease Therapeutics. Drugs. 2023; 83(7):569-576.
8. Biogen. Available at: https://investors.biogen.com/news-releases/news-release-details/eisai-files-marketing-authorization-application-lecanemab. Accessed on 15th September 2023.
9. Man VH, He X, Han F, et al. Phosphorylation at Ser289 Enhances the Oligomerization of Tau Repeat R2. J Chem Inf Model. 2023 Feb 27;63(4):1351-1361.
10. Povova J, Ambroz P, Bar M, et al. Epidemiological of and risk factors for Alzheimer's disease: a review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012 Jun;156(2):108-14.
11. Masters CL, Bateman R, Blennow K, et al. Alzheimer's disease. Nat Rev Dis Primers. 2015 Oct 15;1:15056.
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