Monoclonal antibody | |
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Type | ? |
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Other names | MTAU-9937A; MTAU9937A; RG-6100; RG6100; RO-7105705; RO7105705 |
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Semorinemab (INN , USAN ; developmental code names MTAU-9937A, RG-6100, RO-7105705) is a monoclonal antibody against tau which was under development for the treatment of Alzheimer's disease but was discontinued. [1] [2] [3] It binds to the N-terminus of all six isoforms of tau. [2] [3] The drug was ineffective in the treatment of Alzheimer's disease in two phase 2 clinical trials. [2] [3] Clinical development of semorinemab for Alzheimer's disease was discontinued in February 2024. [1]
Tis has led to a number of frst-generation tau-targeting immunotherapies targeting the N-terminus such as semorinemab [58], tilavonemab [59], zagotenemab [60] and gosuranemab [61]. However, these antibodies achieved negative outcomes in AD and primary tauopathy clinical trials, showing lack of efcacy and missing their primary endpoints. An exception is semorinemab which, in one of the two phase 2 trials, improved cognitive function (one of the co-primary endpoints) without afecting the activities of daily living or any of the prespecifed secondary outcomes [62]. Tese negative outcomes were achieved despite clear evidence of target engagement, with N-terminal tau decreasing in CSF and increasing in plasma. In the most extreme example, gosuranemab decreased N-terminal tau in CSF by 98% (11% increase for placebo) without showing clinical efcacy in progressive supranuclear palsy (PSP).