One of the assets shelved by Eli Lilly is a gene therapy for dementia, which it obtained in its $1.04-billion acquisition of Prevail Therapeutics in late 2020.
As it works to expand its GLP-1 portfolio into a pipeline-in-a-product franchise, Eli Lilly is cleaning up its clinical pipeline, discontinuing three assets—including one dementia gene therapy.
That asset, LY3884963, came to the company from Prevail Therapeutics, which Lilly swallowed for $1.04 billion in December 2020. LY3884963 was still in the pharma’s pipeline as of its Q3 earnings report in October 2025 but had been removed from a similar presentation Wednesday.
Before being discontinued, Lilly was running a Phase 1/2 study for LY3884963 in patients with frontotemporal dementia who harbor mutations to the progranulin gene, a key player in neuron survival. A listing for this trial in a federal database indicates the study is still “recruiting” and has not yet been terminated. The study’s completion date is set for April 30, 2031.
A spokesperson for Lilly confirmed the discontinuation of LY3884963 in frontotemporal dementia to Fierce Biotech. The move, the spokesperson added, was “due to a lack of compelling efficacy in the studied patient population. The decision was not due to any safety concern.” Lilly will share related data at an upcoming medical congress.
Aside from LY3884963 Lilly has also scrapped the CD19 antibody LY3541860, for which the pharma had run two Phase 2 studies. The first looked at its potential in treating relapsing multiple sclerosis and has a primary completion date of August 2027, while the second focused on active rheumatoid arthritis and should have delivered preliminary data last November.
Lilly has also dropped 225Ac-PSMA-62, an actinium-225-based radioligand therapy that targets the PSMA protein. The pharma had been running a Phase 1 study for the asset to test its therapeutic value in hormone-sensitive and metastatic castration-resistant prostate cancer.
As in the case of the dementia gene therapy, the decision to scrap both the antibody and the radioconjugate was due efficacy, which the spokesperson told Fierce failed to meet the pharma’s bar for progression. Safety did not factor into the discontinuation.
Lilly’s clinical clean-up comes as it seeks to transform its GLP-1 franchise, anchored by its tirzaptide brands Mounjaro and Zepbound, into a pipeline-in-a-product. Phase 3b data released last month showed that tirzepatide, when combined with the autoimmune drug Taltz, led to a 50% improvement in psoriatic arthritis versus Taltz alone.
In an investor call on Wednesday, Chief Scientific and Product Officer Dan Skovronsky said this outcome sheds “further light on how incretins may have a positive effect on other diseases independent from weight loss.” Lilly is also testing tirzepatide with the interleukin blocker Omvoh in Phase 3b trials of Crohn’s disease and ulcerative colitis, Skovronsky added.
