Eli Lilly Halts Development of Phase 2 Pain Candidate in Pipeline Shakeup

Eli Lilly has announced the discontinuation of its phase 2 P2X7 inhibitor, LY3857210, for pain indications, marking another significant shift in the company's pain pipeline this year. The decision comes as part of Lilly's ongoing efforts to streamline its research and development portfolio.

P2X7 Inhibitor Falls Short of Expectations

LY3857210, originally licensed from Asahi Kasei Pharma in 2021 for $20 million upfront, failed to meet Lilly's internal benchmarks for success. A Lilly spokesperson stated, "P2X7 data did not meet our high internal bar for success and is being removed from the pipeline for pain." The company is currently evaluating potential next steps for the program, including exploring additional indications beyond pain management.

The asset had been undergoing evaluation for osteoarthritis, diabetic neuropathic pain, and chronic back pain as part of Lilly's phase 2 chronic pain master protocol. Despite the setback in pain indications, the licensing agreement with Asahi Kasei Pharma remains intact, according to an Asahi Kasei spokesperson.

Lilly's Evolving Pain Pipeline

This latest development follows a series of changes to Lilly's pain research portfolio:

1. Earlier this year, Lilly discontinued mazisotine, a non-opioid pain candidate licensed from Centrexion Therapeutics in 2019 for $47.5 million upfront.

2. The company added a phase 1 NaV1.8 inhibitor, STC-004, to its pipeline following the acquisition of SiteOne Therapeutics. This asset targets the same mechanism as Vertex's recently approved pain treatment, Journavx.

3. Lilly's current pain pipeline includes a phase 1 AT2R antagonist licensed from Confo Therapeutics in 2023, a phase 2 epiregulin-targeting antibody called fepixnebart, and the oral GLP-1 candidate orforglipron, which is undergoing two phase 3 trials for osteoarthritis pain.

Challenges in P2X7 Drug Development

The discontinuation of LY3857210 highlights the ongoing challenges in developing drugs targeting P2X7 receptors. Despite their implication in various diseases, including neurodegenerative conditions and cancer, no P2X7-targeting drugs have received regulatory approval to date.

Previous attempts by other pharmaceutical companies to develop P2X7 inhibitors have also faced setbacks. GSK's efforts in chronic pain over a decade ago were halted after disappointing phase 1 results. AstraZeneca's P2X7 candidate for rheumatoid arthritis failed to outperform placebo in phase 2 trials, leading to its discontinuation.

As Eli Lilly continues to refine its research focus, the pharmaceutical industry watches closely to see how these pipeline adjustments will shape the future of pain management therapies.