Eli Lilly Enters $410M Licensing Deal with Asahi Kasei for Oral P2X7R Antagonist AK1780 in Chronic Pain

Compiled by | newborn

On January 28, Eli Lilly and Asahi Kasei Pharma Corporation of Japan announced a licensing agreement under which Eli Lilly will obtain exclusive rights to AK1780 from Asahi Kasei. AK1780 is an orally bioavailable P2X7 receptor antagonist that has recently completed Phase 1 single and multiple ascending dose studies as well as clinical pharmacology studies. The P2X7 receptor has been implicated in neuroinflammation, a driver of various chronic pain conditions.

Under the terms of the agreement, Eli Lilly will be responsible for the future global development and regulatory activities for AK1780. Eli Lilly will pay Asahi Kasei a $20 million upfront payment, and Asahi Kasei will also be eligible to receive up to $210 million in potential development and regulatory milestone payments. Asahi Kasei will retain the rights to promote AK1780 in Japan and China (including Hong Kong and Macau). If AK1780 is successfully commercialized, Asahi Kasei will be eligible to receive up to $180 million in potential sales milestones, as well as tiered royalties ranging from the mid-single digits to the low double digits.

P2X7R is an ATP-gated non-selective cation channel associated with autoimmune diseases, chronic pain, and neurodegenerative disorders. AstraZeneca previously developed a P2X7R antagonist, AZD9056, which advanced to Phase 2b clinical trials for rheumatoid arthritis but was terminated due to its failure to demonstrate efficacy superior to placebo. Following AstraZeneca, P2X7R antagonist programs from several other pharmaceutical giants, including GlaxoSmithKline, Johnson & Johnson, and Pfizer, have also entered clinical development.

Although the initial clinical trials of P2X7R antagonists targeted rheumatoid arthritis, Eli Lilly considers AK1780 a potential therapeutic agent for neuroinflammatory pain. This focus on such patients is grounded in evidence from animal models and other sources, which suggest that targeting P2X7R may alleviate inflammatory pain.

However, clinical evidence supporting the use of P2X7R antagonists for the treatment of neuropathic pain remains limited. Asahi Kasei has completed a Phase 1 study of AK1780, including single and multiple ascending dose cohorts and clinical pharmacology assessments, but has not yet publicly disclosed the data. Other research groups are also evaluating P2X7R antagonists in conditions such as autoimmune diseases and depression.

This transaction will add a new asset to Eli Lilly’s pain pipeline. Currently, the pipeline comprises multiple novel drug candidates with diverse mechanisms of action, including three agents in Phase I clinical trials (a PACAP38 antibody, an SSTR4 agonist, and a TRPA1 antagonist), and one TGFα antibody in Phase II clinical trials. The lead candidate, the anti-NGF antibody tanezumab, is being co-developed with Pfizer and is currently under review by the U.S. FDA for the treatment of osteoarthritis pain. Although its PDUFA target date was December 2020, no regulatory decision has been issued to date.

The ruling on tanezumab could have implications for NGF-inhibiting analgesics. Nearly a decade ago, this field was overwhelmed by safety concerns, leading to prolonged and slow late-stage clinical trials. Eli Lilly and Pfizer hoped to reverse the downturn, but poor Phase 3 safety data released in early 2019 deterred analysts.

Despite the bleak outlook, Eli Lilly and Pfizer have decided to press on, hoping to secure FDA approval for low-dose tanezumab. A competing drug from Regeneron and Teva also emerged as a strong contender after its Phase 3 clinical data were released last August. At the time, Regeneron CEO Len Schleifer told Endpoints News that the company would closely monitor the FDA’s decision on tanezumab.

References:

1.Lilly and Asahi Kasei Pharma Announce License Agreement for Chronic Pain Drug Candidate

2.Lilly lands clinical-phase pain drug via deal with Asahi Kasei

3.Lilly attempts to revive an old idea for tackling pain, licensing PhI program from Japan’s Asahi Kasei Pharma