Decibel Therapeutics reported positive top-line results from an interim analysis of its ongoing Phase 1b clinical trial of DB-020, a novel, proprietary formulation of sodium thiosulfate (STS) designed to protect against hearing loss in cancer patients receiving cisplatin chemotherapy. Cisplatin, one of the most commonly used chemotherapeutic agents, has severe dose-limiting side effects, including ototoxicity, which leads to permanent hearing loss in many patients. There are no approved therapies to prevent or treat cisplatin-induced ototoxicity.

Patients enrolled in the Phase 1b clinical trial were randomized to receive one of two doses of DB-020 in one ear while the contralateral ear received placebo, enabling each patient to serve as their own control. Patients were administered DB-020 and placebo up to three hours prior to each cisplatin infusion. Consistent with the results of a Phase 1 clinical trial of DB-020 previously completed by the Company in healthy volunteers, data from the interim analysis demonstrated that DB-020 was well tolerated, with adverse events generally mild to moderate.

In the data from the interim analysis, 88% of patients experienced ototoxicity in their placebo-treated ear, and of these patients, 87% were partially or completely protected from ototoxicity in their DB-020-treated ears. The interim analysis includes data collected as of February 4, 2022 from 19 cisplatin-naïve cancer patients being treated with high doses of cisplatin every 21 or 28 days. Of the 19 patients in the interim analysis, 17 patients had evaluable audiograms at baseline and after being dosed with DB-020 in one ear and placebo in the contralateral ear in conjunction with their prescribed infusion of cisplatin chemotherapy.

Ototoxicity was defined according to the American Speech-Language-Hearing-Association (ASHA) criteria for significant ototoxic change. Key findings: DB-020 was generally well tolerated, with no significant safety issues observed; DB-020, administered prior to cisplatin, had no apparent effect on systemic cisplatin levels; 13 of 17 (76.5%) patients experienced cisplatin-induced ototoxicity in the placebo ear after the first cycle of cisplatin; 15 of 17 (88.2%) patients experienced cisplatin-induced ototoxicity in the placebo ear by the last evaluable test; Placebo-treated ears lost approximately 30dB on average from baseline in high frequencies, shifting patients from normal or slight hearing loss to moderate hearing loss (two hearing loss categories) on average; In the 15 patients who experienced ototoxicity in the placebo ear by the last evaluable test, DB-020 protected 13 (87%) from ototoxicity in their DB-020-treated ear; 8 of 15 (53.3%) were completely protected, and 5 of 15 (33.3%) were partially protected. (Complete protection was defined as no change in hearing from baseline in the ear that received DB-020 according to the ASHA ototoxicity criteria in the clinically assessed range.); Ears treated with DB-020 lost approximately 8dB on average from baseline; DB-020 reduced cisplatin-induced loss of speech audibility by 80% as measured by the Speech Intelligibility Index, suggesting treatment with DB-020 may reduce the risk of needing assistive hearing devices after receiving cisplatin.