HSK-21542 (Anrikefon): A Comprehensive Clinical and Pharmacological Profile of a Novel Peripherally Restricted KOR Agonist

I. Executive Summary

HSK-21542, developed by Sichuan Haisco Pharmaceutical under the trade name Anrikefon, is a novel, intravenously administered, peripherally restricted kappa-opioid receptor (KOR) agonist.[1] It represents a significant advancement in the fields of analgesia and antipruritics, engineered to provide potent therapeutic effects while circumventing the severe central nervous system (CNS) liabilities that have limited the use of traditional mu-opioid receptor (MOR) agonists and earlier generations of KOR agonists.[4] Its core value proposition lies in its ability to selectively target peripheral KORs, thereby blocking pain and itch signals at their source without crossing the blood-brain barrier, thus avoiding side effects such as respiratory depression, addiction, dysphoria, and hallucinations.[4]

The clinical development program for HSK-21542 has yielded robust evidence of its efficacy and safety. In pivotal Phase III trials for the management of postoperative pain following abdominal surgery, HSK-21542 demonstrated statistically significant superiority over placebo. Furthermore, it proved to be non-inferior to the active comparator tramadol in analgesic efficacy but with a markedly improved safety profile, particularly inducing fewer gastrointestinal adverse events.[4] These compelling results led to its regulatory approval in China in May 2025 for the treatment of postoperative pain, where it is uniquely classified as a non-narcotic "white prescription" analgesic, greatly facilitating its clinical adoption.[1]