Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
This is a monoclonal antibody directed primarily against soluble protofibrillar and fibrillar species of Aβ. It is relatively inactive against Aβ monomers and small oligomeric aggregates. This humanized antibody was engineered on an IgG4 backbone. Its parent murine mAb, SAR255952, is reported to have low effector function, which is thought to reduce the risk of amyloid-related imaging abnormalities (ARIA). SAR228810 reportedly has low binding affinity for activating FcγRs on human microglia and no binding to complement C1q, a pro-inflammatory component of the innate immune system. The rationale is that these features confer less risk of a proinflammatory response leading to vasogenic edema and cerebral microhemorrhage (AAIC 2013 abstract).
A multicenter Phase 1 trial testing six ascending doses of intravenous infusion and two doses of subcutaneous injection is testing safety, pharmacokinetics, and pharmacodynamics of SAR228810 in 48 patients at sites in Sweden and other countries. See trials listed on clinicaltrials.gov.
- Aisen PS, Vellas B. Passive immunotherapy for Alzheimer's disease: what have we learned, and where are we headed?. J Nutr Health Aging. 2013 Jan;17(1):49-50. PubMed.