Solanezumab (proposed INN, LY2062430[1]) is a monoclonal antibody being investigated by Eli Lilly as a neuroprotector[2] for patients with Alzheimer's disease.
[3][4] The drug originally attracted extensive media coverage proclaiming it a breakthrough, but it has failed to show promise in Phase III trials.
[5][6] Solanezumab was safely used in combination with approved Alzheimer's disease treatment, such as acetylcholinesterase inhibitors or memantine, in the clinical trials.
[1][7][8] Solanezumab binds the amyloid-β peptides that aggregate and form plaques in the brain that are an early pathological feature of Alzheimer's disease.
[11] Solanezumab binds the central epitope of monomeric amyloid-β, KLVFFAED, (PDB ID 4XXD[12]) with picomolar affinity.
[15] It is covered under the patent US 7,195,761 B2, which was filed in 2002 by Eli Lilly, Indianapolis, IN, and Washington University in St.
Treatment with a murine analog of solanezumab (m266) lead to an increase in plasma amyloid beta, which was all bound to m266.
[14] In a single-dose, placebo-controlled study (H8A-LC-LZAH) in 19 patients with mild-to-moderate Alzheimer's disease, solanezumab was well tolerated over the whole dose range.
[7] 52 patients with mild-to-moderate Alzheimer's disease underwent a parallel group, double-blind, randomized, placebo controlled phase 2 trial.
Patients with mild-to-moderate Alzheimer's disease received either placebo or 400 mg solanezumab infusions every 4 weeks over 18 months.
[19][20] In July 2023, the final data showed that it did not slow cognitive decline as compared with placebo over a period of 240 weeks in persons with preclinical Alzheimer's disease.