Two AD drugs have been granted BTD by the FDA recently, namely Eisai/Biogen's Lecanemab (BAN2401) and Eli Lilly's Donanemab. Lecanemab is known to be an anti-amyloid β(Aβ) fibril antibody under development for the treatment of AD, Donanemab is recognized a humanized antibody of IgG1 subtype that targets a specific form of Aβ protein (i.e., pyroglutamate at the 3rd position of Aβ, hereinafter referred to as N3pG-Aβ). The form of N3pG-Aβ is highly associated with occurrence of aggregation, which is a target of AD treatment under the spotlight.
Lecanemab (BAN2401) is accepted to be a humanized antibody of the mouse monoclonal antibody mAb158 developed by BioArctic based on its proprietary antibody technology, targeting β amyloid (Aβ) fibrils. In 2007, Eisai came to terms with BioArcticto to obtain the rights of global research, development, production and sales to the drug. In 2014, Eisai and Biogen achieved consent for joint development and commercialization of the drug.
The BTD for Lecanemab Was Bestowed Based on the Results of Study 201, which is a Phase 2b clinical trial. Study 201 is established as a randomized, double-blind proof-of-concept clinical trial involving 856 patients with MCI due to AD or mild AD. This study is performed to evaluate the effect of Lecanemab in patients with early AD on mitigating brain amyloid (aβ) and clinical decline. The pre-set analysis plan has suggested that in the highest dose group, the clinical decline of multiple clinical and biomarker endpoints have been consistently brought down.
At present, two Lecanemab-related Phase 3 clinical trials named Clarity AD and AHEAD3-45 are in progress. Clarity AD is designed to be an 18-month placebo-controlled, double-blind, parallel group, open-period extension trial. It has completed the enrollment of 1,795 symptomatic early AD patients, to look at the safety and efficacy of Lecanemab in subjects with early AD (EAD). AHEAD 3-45, consisting of two trials A3 and A45, aims to assess the efficacy and safety of Lecanemab in (asymptomatic) patients with AD in the preclinical stage but with amyloid in the brain.
Donanemab's BTD by the FDA is based on the results of its Phase II clinical trial, TRAILBLAZER-ALZ. The study recruited 257 patients with AD, of which 131 received Donanemab treatment and 126 accepted placebo for control. In January this year, Eli Lilly announced that the Phase II clinical TRAILBLAZER-ALZ has come up to the primary clinical endpoint.
The results show that: Following 76 weeks of treatment, patients who received Donanemab experienced a reduction in Integrated Alzheimer's Disease (AD) Rating Scale (iADRS) by 32% compared with the placebo group, reaching the primary endpoint. Meanwhile, PET imaging suggested that Donanemab can quickly remove amyloid deposits in the patient's brain: Following 6 months of treatment, 40% of patients tested negative in PET; Following 18 months of treatment, 68% of patients met a level of negative PET result.
Currently, a Donanemab-related randomized double-blind, placebo-controlled Phase 3 clinical trial is undergoing to further test its safety, tolerability and efficacy.
There is a new AD drug approved at home and abroad: GV-971 VS Aduhelm
Alzheimer's disease (AD), a degenerative brain disease characterized by progressive neurological degeneration, can typically lead to impaired thinking, memory and independence, and is deemed as the third leading cause of death in the elderly worldwide, next only to cardiovascular and cerebrovascular diseases and cancer. It is reported in World Alzheimer Report 2018 that there are at least 50 million dementia patients in the world, and it will increase to nearly 150 million by 2050 based on an estimation, of which AD patients represent approximately 60%-70%.
Currently, the exact cause of AD remains unknown, which may be asso...
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