Sound Pharmaceuticals was recently awarding funding up to $1.6 million to support the early development of its lead drug candidate SPI-1005 for cystic fibrosis (CF) patients who are taking the antibiotic tobramycin to treat lung infections or acute pulmonary exacerbations.
One major side effect of tobramycin (brand names Tobi or Tobrex) is the damage it can cause to the inner ear, called ototoxicity.
The funding came from Cystic Fibrosis Foundation Therapeutics (CFFT), the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation.
Sound’s randomized, double-blind, placebo-controlled, Phase 1b clinical trial (STOP Ototoxicity, NCT02819856) will evaluate the safety, pharmacokinetics (how the drug moves in the body) and pharmacodynamics (how the body reacts to the drug) of SPI-1005 in 100 CF patients with active pulmonary exacerbation and who are receiving tobramycin intravenously (IV).
The trial’s primary endpoint is the number of participants with adverse events as a measure of safety and tolerability at seven weeks of treatment. Another primary endpoint is the safety and tolerability of SPI-1005 at three different dose levels (200, 400, and 600 mg).
The study will assess the incidence and severity of hearing loss, tinnitus (ringing in the ears), dizziness, or vertigo due to IV tobramycin treatment, and the effects of SPI-1005 in reducing these symptoms.
Patrick Flume, MD, professor of medicine and pediatrics at the Medical University of South Carolina (MUSC) in Charleston will lead the clinical trial. Flume is an international expert in cystic fibrosis and pulmonary disease, and has co-chaired the development of the CF Foundation’s care guidelines on the treatment of pulmonary exacerbations.
“This is the first comprehensive U.S. study of ototoxicity in the CF population and we are pleased to be leading it,” Flume said in a press release.
Jonathan Kil, MD, Sound Pharmaceuticals’ co-founder, CEO, and chief medical officer, said the company is “thrilled to have the support of the CF Foundation and Dr. Flume on this groundbreaking study of tobramycin-induced ototoxicity.”
Ototoxicity is a type of ear poisoning caused by exposure to drugs or chemicals that damage the inner ear or the vestibulo-cochlear nerve (the nerve sending balance and hearing information from the inner ear to the brain).
Aminoglycosides, such as tobramycin or amikacin, are toxic to the hair cells of the cochlea and can cause irreversible sensorineural hearing loss. CF patients are extremely vulnerable to ototoxicity when they receive repeated courses of these drugs through inhalation and intravenous routes, starting at a young age.
Ototoxicity can be temporary or permanent and may require a cochlear implant. Currently, there are no drugs approved by the U.S. Food and Drug Administration (FDA) for the prevention or treatment of any type of sensorineural hearing loss or tinnitus.
SPI-1005 is an investigational drug that contains an orally available small molecule that mimics and induces glutathione peroxidase (GPx) activity. GPx1 activity is diminished after ototoxic insults that cause sensorineural hearing loss and tinnitus.