Name:	Solanezumab
Other Names:	LY2062430
Therapeutic Applications:	Mild to moderate Alzheimer disease
Therapy Types:	Protein: humanized monoclonal antibody against Aβ.
Mechanisms:	Designed to bind and remove the Aβ peptide that accumulates in the brain.
Development Status:	investigational in U.S.
FDA Phase:	Phase III
Primary Medical Role:	Immunotherapy approaches to the treatment of Alzheimer disease are based on the ability of antibodies raised against Aβ peptides to bind to and clear Aβ from the brain, thus removing the peptide and inhibiting the damage to neurons that Aβ inflicts. Solanezumab is a passive immunotherapy approach, in which patients are treated with humanized monoclonal antibodies with specificity to Aβ peptides. The treatment with antibodies should bind and clear Aβ, with the potential added benefit of a better safety and tolerability profile.
Role in Alzheimer's Disease:	Solanezumab binds specifically to soluble amyloid-β and therefore may act to draw the peptide away from the brain through the blood to be cleared peripherally. In short-term clinical studies, solanezumab appeared to have dose-dependent effects on amyloid-β in blood and cerebrospinal fluid. The correlation between total plasma Aβ1-42 after treatment and baseline amyloid plaque burden by single photon emission tomography (SPECT) scanning, together with the dose-dependent increase in unbound CSF Aβ1-42, suggest that this antibody may mobilize Aβ1-42 in AD plaques, and normalize soluble CSF Aβ1-42 in AD patients. The clinical studies to date have been too short to evaluate any potential delay in the progress of Alzheimer disease. Also see ARF related news story and ARF news story. In a 21-day study, 19 mild to moderate AD patients were tested with single dose infusions of LY2062430 (solanezumab), dose ranging from 0.5 to 10 mg/kg (Siemers et al., 2010). The highest dose elicited infusion reaction, but the lower doses were well tolerated. CSF and plasma Aβ increased after treatment, consistent with antibody binding and stimulated clearance, with no evidence of either cognitive efficacy or adverse effects.
Side Effects:	To date, the only side effect experienced in clinical studies that appeared to be associated with solanezumab treatment has been mild chills consistent with an infusion reaction; other side effects reported in the Phase 2 study include nausea, vomiting, headache, back pain, and cough.
Companies:	Eli Lilly and Company
Notes:	This entry was updated on September 29, 2010.

References

Siemers ER, Friedrich S, Dean RA, Gonzales CR, Farlow MR, Paul SM, Demattos RB. Safety and changes in plasma and cerebrospinal fluid amyloid beta after a single administration of an amyloid beta monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol. 2010 Mar-Apr;33(2):67-73. Abstract

Siemers ER, Friedrich S, Dean RA, Sethuraman G, DeMattos R, Jennings D, Tamagnan G, Marek K, Seibyl J. 2008. Safety, tolerability and biomarker effects of an Abeta monoclonal antibody administered to patients with Alzheimer's disease. ICAD July 30, 2008 (Chicago) Abstract P4-346