Eli Lilly has halted development of a phase 2 P2X7 inhibitor for pain, the company confirmed to Fierce Biotech, in the latest shakeup to a pipeline that has already seen significant pivots this year.
The asset, coded LY3857210, was originally licensed from Asahi Kasei Pharma in 2021. The Japanese pharma received $20 million upfront for the candidate, then known as AK1780, and had already put the molecule through phase 1 testing.
“P2X7 data did not meet our high internal bar for success and is being removed from the pipeline for pain,” a Lilly spokesperson told Fierce. “Lilly is assessing next steps for the program, including possible additional indications.”
Though Lilly is no longer pursuing LY3857210 in pain, the licensing pact remains intact, an Asahi Kasei spokesperson confirmed to Fierce.
Lilly had been putting the asset through its paces in osteoarthritis, diabetic neuropathic pain and chronic back pain as part of the Big Pharma’s phase 2 chronic pain master protocol.
LY3857210 joins mazisotine in Lilly’s pain scrapheap. The Indianapolis drugmaker dropped the non-opioid pain candidate last quarter after licensing it from Centrexion Therapeutics in 2019 for $47.5 million upfront.
In parallel with mazisotine’s shelving, Lilly added a phase 1 NaV1.8 inhibitor from its SiteOne Therapeutics acquisition to its pipeline. That asset, STC-004, hits the same target as Vertex’s pain treatment Journavx.
In addition to the NaV1.8 inhibitor, Lilly’s pain pipeline also includes a phase 1 AT2R antagonist licensed from Confo Therapeutics in 2023, a phase 2 epiregulin-targeting antibody called fepixnebart, and star oral GLP-1 candidate, orforglipron, which Lilly is testing in two phase 3 osteoarthritis pain trials.
P2X7 receptors have been implicated in a wide swath of diseases, including neurodegenerative conditions and cancer. However, no drugs targeting P2X7 have been approved, though not for lack of trying.
GSK once tested its own P2X7 prospect in chronic pain more than a decade ago, but cut the candidate after an unimpressive phase 1 showing. AstraZeneca, meanwhile, pushed a P2X7 candidate through phase 2 for rheumatoid arthritis, but the company then dropped the asset after it failed to top placebo.