As Eli Lilly awaits an FDA approval decision for its oral GLP-1 orforglipron, the pharma has discarded three clinical-stage drugs, including a gene therapy from its $1 billion acquisition of Prevail Therapeutics.
The therapy was being studied as a treatment for a specific type of frontotemporal dementia (FTD) that relates to changes in the progranulin (GRN) gene. Aptly named FTD-GRN, the neurodegenerative disease is primarily inherited and can lead to changes in behavior and executive functioning.
Lilly’s gene therapy for the condition stems from its $1 billion-plus buyout of Prevail Therapeutics back in 2020. Dubbed LY3884963—and formerly known as PR006—the therapy entered a phase 1/2 trial in 2020 and was in the later stage of the study. The trial included five different treatment cohorts across various doses, dosing manners and phases of disease.
“Lilly discontinued GRN gene therapy in frontotemporal dementia due to a lack of compelling efficacy in the studied patient population. The decision was not due to any safety concern,” a spokesperson told Fierce.
The study was slated for a primary readout in 2031, according to ClinicalTrials.gov. The trial’s main goal was to assess the safety and effect of the therapy on GRN levels. Patients already enrolled in the study will be included in a safety follow-up period, according to the Lilly spokesperson.
“We aim to leverage insights gained from this program in upcoming interventions and are planning to share the data at a forthcoming scientific meeting,” the spokesperson added.
The big pharma is still continuing development for several other gene therapies, including a mid-stage GBA1 gene therapy that Prevail had touted as its lead asset. The candidate is being studied in trials for both Parkinson’s disease and Gaucher disease type 1.
And just last week, Lilly inked a deal potentially worth more than $1 billion to get in on the development of a genetic medicine for hearing loss from Seamless Therapeutics.
Next on the chopping block is LY3541860, an anti-CD19 antibody tested out in mid-stage studies for both multiple sclerosis (MS) and rheumatoid arthritis (RA).
In the RA trial, the autoimmune asset was being evaluated for its ability to impact disease activity compared to baseline among 35 patients, according to ClinicalTrials.gov. The phase 2a study’s primary readout was scheduled for November of last year.
“The termination was not safety-driven,” Lilly’s spokesperson said. “The asset did not meet Lilly’s high bar for continued development.”
Meanwhile, the MS phase 2a/2b trial for LY3541860 is slated to readout in August of 2027, according to the federal database. The expected four-year study aimed to enroll 200 patients and was most recently listed as "recruiting."
Previously, preclinical models demonstrated that the anti-CD19 antibody was a “highly potent B cell inhibitor that may have potential to demonstrate improved efficacy over currently available B cell-targeting therapies in treatment of autoimmune conditions without causing B cell depletion.”
Lastly, Lilly is ditching AC-225-PSMA-62, an investigational radioligand therapy that was being studied in a phase 1/2 trial for prostate cancer. More specifically, the trial enrolled patients with prostate-specific membrane antigen (PSMA)-positive cancer with limited spread. The study’s primary readout was scheduled for September 2027.
AC-225-PSMA-62 didn’t meet Lilly’s “bar for differentiated efficacy to advance to phase 2,” according to the spokesperson. The termination wasn’t related to “any new or unexpected safety findings,” they added.
When asked if any layoffs were associated with the pipeline cuts, the spokesperson said, “There are no large-scale workforce reductions underway at Lilly. We continuously evaluate our business model and routinely make workforce adjustments to enhance our speed, agility and ability to deliver the best medicines to patients.”
In the most recent quarter, Lilly’s R&D spend rose 26% to $3.8 billion, or 20% of revenue, according to the company’s earnings report. Over the last few years, the tirzepatide developer has zeroed in on its next-gen obesity candidates, including small molecule orforglipron. Lilly has snared a Commissioner’s National Priority Voucher that could accelerate an approval decision for orforglipron.