Eli Lilly Trims Pipeline, Axing Alzheimer's and Obesity Candidates

Eli Lilly, a prominent player in the pharmaceutical industry, has announced significant changes to its drug development pipeline, removing several candidates in key therapeutic areas. The company's fourth-quarter update reveals a strategic realignment, particularly affecting its Alzheimer's disease and obesity programs.

Alzheimer's Program Setback

Eli Lilly has removed ceperognastat, an oral O-GlcNAcase anti-tau agent, from its Alzheimer's disease pipeline. This decision follows the compound's failure to slow clinical decline in early symptomatic Alzheimer's patients during a phase 2 trial. Despite initial promise in preclinical studies, where ceperognastat showed a 50% reduction in tau pathology and a 40% decrease in brain atrophy, these benefits did not translate to human trials.

Dr. Daniel Skovronsky, Chief Scientific Officer at Lilly, had previously highlighted biomarker data suggesting "potential impacts on tau pathology, brain volume and neuro-inflammation." However, the company has now decided to discontinue the program as the phase 2 trial concludes this month.

This setback marks another challenge in Lilly's tau-focused research efforts. In 2021, the company removed zagotenemab, another tau drug candidate, from its pipeline. Despite these obstacles, Lilly maintains that tau remains "a high conviction target" in their Alzheimer's research strategy.

Obesity and Other Pipeline Adjustments

In the obesity therapeutic area, Lilly has discontinued a dual amylin calcitonin receptor agonist (DACRA) from its phase 1 pipeline. This compound, known as DACRA QW II and LY3541105, was part of a collaboration with KeyBioscience that began in 2017. The decision to remove this candidate comes as Lilly focuses on more promising programs, such as tirzepatide, the active ingredient in its products Mounjaro and Zepbound.

Additionally, Lilly has made cuts in other areas of its pipeline:

1. Ucenprubart (LY3454738), a CD200R1 agonist being studied for eczema, was removed after the company halted enrollment in its phase 2 trial last month.

2. Volenrelaxin, which was under investigation for heart failure and chronic kidney disease (CKD), was terminated due to "a lack of foreseeable clinical benefit" in the target population. This decision followed the termination of a related heart failure study that showed no benefit in an overlapping patient group.

These pipeline adjustments reflect Eli Lilly's ongoing efforts to optimize its research and development portfolio, focusing resources on the most promising candidates and therapeutic areas. As the pharmaceutical landscape continues to evolve, such strategic decisions are crucial for maintaining competitiveness and driving innovation in drug development.