ORC-13661

ORC-13661 is an investigational drug developed to protect against hearing loss caused by aminoglycoside antibiotics and cisplatin. It works by blocking the mechanoelectrical transducer (MET) channel in sensory hair cells of the inner ear, preventing the entry of ototoxic compounds. ## Development and Current Status ORC-13661 was originally derived from PROTO-1, a compound identified through a large-scale screen using zebrafish larvae. The drug was developed at the University of Washington by researchers Edwin Rubel and David Raible, who co-founded Oricula Therapeutics in 2013 to commercialize the compound. The drug has successfully completed Phase 1 clinical trials in normal human volunteers, demonstrating favorable pharmacokinetics with linear dose proportionality and a long half-life (>72 hours) that facilitates daily oral dosing. It was well-tolerated with no definite drug or dose-related adverse events, even at doses greater than threefold above the expected clinical dose. A Phase 2 "proof of concept" clinical trial is planned to further define the drug's effectiveness. As of May 2025, ORC-13661 is being investigated in clinical trial NCT05730283 for the prevention of ototoxicity in patients with nontuberculous mycobacteria (NTM) infections treated with intravenous amikacin. ## Mechanism of Action ORC-13661 functions as a high-affinity permeant blocker of the mechanoelectrical transducer (MET) channel in outer hair cells. This mechanism suggests it reduces the toxicity of aminoglycosides by directly competing for entry at the level of the MET channel, and protects against cisplatin through a MET-dependent mechanism. Preclinical testing has demonstrated that ORC-13661 provides robust protection of hair cells against both aminoglycoside antibiotics and cisplatin in multiple species: in zebrafish larvae, it protected lateral line hair cells from aminoglycoside toxicity; in mouse cochlear cultures, it protected hair cells against both gentamicin and cisplatin; in rats, it prevented hearing loss in a dose-dependent manner when treated with amikacin. Importantly, ORC-13661 exhibited no interference with the bactericidal effects of aminoglycosides against pathogenic bacteria, meaning it doesn't reduce the effectiveness of the antibiotics in treating infections. If approved, ORC-13661 would be the first FDA-approved medicine specifically designed to prevent hearing loss for patients undergoing aminoglycoside treatment.

Other names

ORC-13661ORC13661ORC 13661BPN-13661BPN13661BPN 13661DB 041DB041DB-041