Synonyms: LY3372993, N3pG-Abeta mAb
Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 3)
Company: Eli Lilly & Co.
LY3372993 is an investigational monoclonal antibody. Lilly's development pipeline lists it as an N3pG-Aβ mAb, suggesting it recognizes a pyroglutamated form of Aβ that is aggregated in amyloid plaques. LY3372993 is a follow-on to donanemab, the company's Phase 3 antibody also against pyroglutamated Aβ.
In November 2018, Lilly started a Phase 1 trial with the intention to compare LY3372993 to placebo in 100 healthy adults and people with MCI due to Alzheimer's disease or mild to moderate AD. The study delivered intravenous infusions of single or multiple escalating doses of LY3372993, and assessed adverse events, LY3372993 exposure in blood, and its ability to affect brain amyloid as measured by florbetapir PET. This study was set to run at eight U.S. centers until October 2020, but in April 2019, Lilly decided to terminate the trial after testing 36 healthy adults, and never enrolled any participants with AD. Study results were not made public.
In July 2020, Lilly began a separate Phase 1 study in people with AD. Thirty participants with clinically diagnosed mild cognitive impairment due to AD, or AD dementia, are receiving multiple escalating doses of antibody, or placebo, over nine months. The primary outcome is the number of serious adverse events; secondary outcomes include pharmacokinetics and change in brain amyloid from baseline to week 25. In 2021, the company added a second part to this trial, enrolling an additional 32 healthy adults of first-generation Japanese origin to receive a single infusion of antibody or placebo. Through 2021 and 2022, enrollment was adjusted upward twice to a final of 224, the treatment period increased to 61 weeks, and the study added subcutaneous dosing. Conducted at nine U.S. sites and three in Japan, the trial will run through January 2024.
In August 2022, Lilly started a Phase 3 and called it TRAILRUNNER-ALZ1. It plans to randomize 400 people with early symptomatic AD to receive antibody or placebo for one year, with dosing by either intravenous infusion or subcutaneous injection. The primary outcome is percentage of patients whose amyloid plaques are cleared by the end of treatment period. Secondary outcomes further measure amyloid clearance, pharmacokinetics, and anti-drug antibodies. The trial includes a year-long blinded extension, where remternetug recipients will cross over to placebo, and placebo recipients to drug. An additional safety cohort of 400 patients will receive open-label intravenous remternetug for one year. The study plans to run at 75 sites in the U.S. and two in Japan. Recruiting began in October, with completion expected in March 2025.
For all trials of LY3372993, see clinicaltrials.gov.
Last Updated: 02 Nov 2022
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