Teng E, Manser PT, Pickthorn K, Brunstein F, Blendstrup M, Sanabria Bohorquez S, Wildsmith KR, Toth B, Dolton M, Ramakrishnan V, Bobbala A, Sikkes SA, Ward M, Fuji RN, Kerchner GA, Tauriel Investigators. Safety and Efficacy of Semorinemab in Individuals With Prodromal to Mild Alzheimer Disease: A Randomized Clinical Trial. JAMA Neurol. 2022 Aug 1;79(8):758-767. PubMed.

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Comments

  1. This negative TAURIEL semorinemab trial in prodromal Alzheimer disease (MMSE 30 to 20) received far more notice than its sibling LAURIET trial (NCT03828747) in mild to moderate AD dementia (MMSE 21 to 16). Yet, in LAURIET there was a highly significant effect on the ADAS-cog11 co-primary after one year of treatment, P value =.0025 (CTAD, Boston, November 2021). There was no significant effect on the ADCS-ADL co-primary or on tau-PET tracer accumulation.

    This low P value in an adequate and well-controlled trial is usually considered compelling by statisticians and “persuasive” by the FDA when they are considering a drug for approval. In addition, the ADAS-cog11 drug-placebo mean difference of 2.96 points is larger than in most any other AD trial, and is at a magnitude considered to be a minimum clinically important difference.

    Most experts appear unimpressed with LAURIET, however, writing it off as a fluke or random outcome; and there seems to be absent enthusiasm for a confirming or validation trial. Maybe the idea of a treatment intended as a disease modifier showing efficacy in a mild to moderate AD trial runs counter to an orthodoxy that we must treat early stage, prodromal, or preclinical AD with so-called disease-modifying treatments and show biomarker changes in order to appreciate any clinical change.

    View all comments by Lon S. Schneider

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This paper appears in the following:

News

  1. TAURIEL Phase 2 Data Published

Therapeutics

  1. Semorinemab