Solanezumab
From Wikipedia, the free encyclopedia
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized |
| Target | Beta amyloid |
| Clinical data | |
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| Identifiers | |
| CAS Number | |
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| Chemical and physical data | |
| Formula | C6396H9922N1712O1996S42 |
| Molar mass | 144084.24 g·mol−1 |
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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]
Aside from Alzheimer's disease, there are other amyloid beta related diseases, in which solanezumab could be used, e.g., Down syndrome or cerebral amyloid angiopathy.[9] However, this has not been studied so far.
Adverse effects
No safety concerns were detected in any of the studies.[1][7][8][10] A few patients suffered from mild infusion reactions that resolved on their own.[1][7] The measured laboratory values and vital signs, showed no changes.[7] Other adverse events that occurred, e.g., headache or hematoma, were not considered as related to treatment.[1][7]
Other anti-amyloid beta antibodies caused amyloid-related imaging abnormalities,[1] which is not the case for solanezumab.[1][7][8]
Pharmacology
Mechanism of action
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.[13] This epitope is known as the nucleation site for Aβ oligomerization, and it is these oligomers of Aβ that are thought to be toxic to neurons.
Solanezumab is thought to act as an "amyloid beta sink"[14] that is "facilitating flux of amyloid beta from a central to peripheral compartment".[14] This increases the peripheral elimination of both amyloid beta and the antibody. Amyloid beta plaques mostly consist of amyloid beta42. Solanezumab binds free amyloid beta which causes amyloid beta42 to solubilize to reestablish the equilibrium in the cerebrospinal fluid.[1]
Manufacturing
Solanezumab is expressed in Chinese hamster ovary cells. The produced antibodies are extracted and purified according to the standard procedures of the art.[9]
Society and culture
Commercial aspects
Solanezumab is developed and investigated by Eli Lilly and Company, Indianapolis, IN.[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. Louis.[9]
In 2011, TPG-Axon Capital funded part of the phase 3 trials. It will receive an estimated $70 million of based on sales milestones after the launch of the product.[16]