LY3202626 / Eli Lilly - LARVOL DELTA

Pharmacological Inventions for Alzheimer Treatment in the United States of America: A Revision Patent from 2010 - 2020. (PubMed, J Prev Alzheimers Dis) - "The molecules Elenbecestat and LY3202626 decreased the burden of Aβ plaques without significant cognitive improvement, Donanemab is in Phase 3 clinical trial, and the FDA has designated it Breakthrough Therapy. CPC-201 and PXT864 demonstrated, in Phase 2, good tolerability and improvement of AD symptoms...The most advanced treatments in their research are those focused on treating Aβ accumulation. More studies are needed to prove the efficacy of the patented molecules."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Immunology • Inflammation

Robust Pharmacodynamic Effect of LY3202626, a Central Nervous System Penetrant, Low Dose BACE1 Inhibitor, in Humans and Nonclinical Species. (PubMed, J Alzheimers Dis Rep) - "LY3202626 is a potent BACE1 inhibitor with high blood-brain barrier permeability. The favorable safety and pharmacokinetic/pharmacodynamic profile of LY3202626 supports further clinical development."

Journal • PK/PD data • Alzheimer's Disease • CNS Disorders • Hepatology • APP

A Study of LY3002813 in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ) (clinicaltrials.gov) - P2 | N=272 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders

Phase II (NAVIGATE-AD study) Results of LY3202626 Effects on Patients with Mild Alzheimer's Disease Dementia. (PubMed, J Alzheimers Dis Rep) - "LY3202626 tested at doses generating 70-90% BACE inhibition was generally well tolerated in this study. LY3202626 treatment did not result in a clinically significant change in cerebral tau burden as measured by flortaucipir nor in change of functional or cognitive decline compared to placebo."

Clinical • Journal • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Mental Retardation • Psychiatry • APP

Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor. (PubMed, J Med Chem) - "We have previously reported the clinical development of LY2811376 and LY2886721. LY2886721 advanced to Phase II, but development was halted due to abnormally elevated liver enzymes. Herein, we report the discovery and clinical development of LY3202626, a highly potent, CNS-penetrant, and low-dose BACE inhibitor, which successfully addressed these key development challenges."

Clinical • Journal • Alzheimer's Disease • CNS Disorders

A Study of LY3202626 in Healthy Participants and Participants With Alzheimer's Disease (clinicaltrials.gov) - P1; N=94; Completed; Sponsor: Eli Lilly and Company; N=136 ➔ 94

Enrollment change • Alzheimer's Disease • CNS Disorders

Excretion, Mass balance and Metabolism of [C] LY3202626 in Humans: An interplay of microbial reduction, reabsorption, and AO oxidation that leads to an extended excretion profile. (PubMed, Drug Metab Dispos) - "A portion of plasma radioactivity was unextractable and presumably bound covalently to plasma proteins. In vitro incubation of LY3202626 in human liver microsomes in the presence of NADPH with dimedone as a trapping agent implicated the formation of the proposed sulfenic acid intermediate."

Journal

Plasma NF-L As a Biomarker for Neurodegeneration in Mild AD Subjects of Phase 2 Navigate-AD Study (AAIC 2019) - P2; "...NAVIGATE-AD is a phase 2 clinical trial (NCT02791191) evaluating the safety and efficacy of the BACE1 inhibitor LY3202626 in mild AD subjects...Clinical outcomes and imaging biomarkers, florbetapir, flortaucipir, florbetapir perfusion PET, and vMRI, were assessed... Baseline plasma NF-L levels associate with baseline clinical and imaging biomarkers of mild AD subjects. Additional results on the longitudinal NF-L change would inform on the utility of plasma NF-L as prognostic or surrogate biomarker for neurodegeneration in AD trials."

Biomarker • Clinical • P2 data