SEATTLE, WASHINGTON — Sound Pharmaceuticals (SPI) will unveil Phase 2b STOP Ototoxicity data, chosen for a podium presentation at the Association for Research in Otolaryngology (ARO) Midwinter Meeting in Anaheim, CA (February 3-7).
This study examined the safety and efficacy of SPI-1005 (ebselen) in preventing and treating aminoglycoside-induced ototoxicity in 60 adult CF patients undergoing intravenous (IV) tobramycin for acute pulmonary exacerbation. Ototoxicity, which includes hearing loss, tinnitus, vertigo, or dizziness, is a common side effect of aminoglycoside antibiotics such as tobramycin, amikacin, gentamycin, and streptomycin.
Presently, there are no FDA-approved therapies for preventing/treating aminoglycoside ototoxicity or any other form of sensorineural hearing loss, tinnitus, or dizziness.
Reducing Aminoglycoside Ototoxicity
In the Phase 1b observational study (N=20), SPI noted ototoxicity rates of 89% and 93% at 2 and 4 weeks after aminoglycoside treatment concluded with a 14-day course of IV tobramycin (Harruff, Journal of Cystic Fibrosis, 2021). The Phase 2b interventional study randomized adult patients to three different ebselen doses or a placebo, administered orally for 21 days within 3 days of commencing IV tobramycin.
In the Phase 2b study (N=40), ototoxicity rates were 73% and 63% at 2 and 4 weeks post-aminoglycoside treatment, marking a statistically significant reduction compared to the Phase 1b study (p-value <0.05). No significant differences were observed in age, IV tobramycin duration, concomitant medications, respiratory status, or baseline hearing loss between the studies.
Interim analysis of Phase 2b results reveals a dose-dependent reduction in ototoxicity rates (from placebo, 200, 400, to 600 mg ebselen), with the 400 and 600 mg doses demonstrating rates of 44% and 43% at 4 weeks (400 mg, p-value <0.05).
To our knowledge, these are the first positive results of an ototoxicity intervention trial in humans undergoing antibiotic treatment for pulmonary exacerbation”
–Jonathan Kil, MD, SPI’s Co-Founder and CEO.
Results from two other preclinical studies on ebselen, a novel anti-inflammatory compound that has shown promise in trials for acute noise exposure, bipolar mania, and Meniere’s disease, will also be presented at the ARO.
The Cystic Fibrosis Foundation (CFF) awarded SPI a $2.2M Therapeutic Development Grant to support these studies. Further trial details (NCT02819856) are available online at www.clinicaltrials.gov or www.soundpharma.com.
Source: Sound Pharmaceuticals
