Sound Pharmaceuticals is pleased to announce that it has enrolled the first patient in its Phase 3 clinical trial involving SPI-1005 for the Treatment of Meniere’s Disease (STOPMD-3). Additionally, this marks the first Phase 3 trial of an investigational new drug for the treatment of Meniere’s Disease (MD).
Prior to STOPMD-3, all US based MD trials involved drugs that were already FDA-approved for other indications. To date, no FDA-approved therapies exist for the treatment of sensorineural hearing loss, tinnitus, vertigo, or dizziness, which together comprise definite or probable MD. “We are grateful to be able to advance this pivotal trial after a 2-year COVID-19 delay” said Jonathan Kil, MD, Co-Founder and CEO. SPI’s clinical data from two completed multi-center, randomized, placebo-controlled studies (Phase 1b and Phase 2b trials) showed that oral delivery of SPI-1005 for 21 or 28 days improved sensorineural hearing loss and tinnitus in patients affected by MD. The STOPMD-3 clinical trial is led by Dr. Paul Lambert, Distinguished Professor in the Dept. of Otolaryngology-HNS at MUSC in Charleston, SC and past President of the American Neurotologic Society. “The unmet need for an effective treatment of Meniere’s has been elusive and we look forward to leading this pivotal study to test whether SPI-1005 is safe and effective,” said Dr. Lambert. Approximately 20 US sites will enroll 200 patients into a randomized double-blind placebo-controlled trial (RCT) where SPI-1005 400 mg twice daily (BID) will be tested against matching placebo. After completing the RCT, patients will be invited to receive open label access to SPI-1005 for 6 to 12 months to further establish the safety of SPI-1005 for intermittent chronic and chronic use.
About the SPI-1005 Phase 1b and Phase 2b clinical trials
The Phase 1b and Phase 2b trials randomized 39 and 126 subjects, respectively to placebo or active doses of SPI-1005, and treated for 21 or 28 days, respectively. Clinically relevant improvements in sensorineural hearing loss were determined using pure-tone audiometry (PTA) and the words-in-noise (WIN) test, two validated measures of hearing sensitivity and specificity administered by an audiologist. Patient-reported outcomes involving tinnitus and vertigo were assessed using the Tinnitus Functional Index (TFI) and Vertigo Symptoms Scale (VSS). Improvement in PTA/WIN and TFI/VSS scores from baseline were compared between SPI-1005 dose groups and the placebo group.
In the Phase 2b study, clinically relevant improvements were observed in low frequency hearing by PTA and WIN scores at 8 weeks after the start of SPI-1005 when compared to placebo. The percentage of subjects showing significant auditory improvements using PTA (≥10 dB gain at one low frequency) in the SPI-1005 400 mg BID dose group rose from 47% at 4 weeks to 61% at 8 weeks, while the percentage showing significant improvements in WIN (≥20% increase in word recognition) rose from 57% at 4 weeks to 68% at 8 weeks. Additionally, SPI-1005 treatment also significantly reduced tinnitus perception or tinnitus loudness (TL) when compared to placebo (p < 0.05). Reductions in TL averaged 1.4 pts in the 400 mg group vs 0.7 pts in the placebo group (30% reduction vs 10% reduction, p <0.02). These Phase 2b data confirmed an initial finding from the Phase 1b trial, that SPI-1005 can reduce tinnitus loudness by clinically relevant levels. These improvements in auditory function further support the use of SPI-1005 to treat sudden sensorineural hearing loss, noise-induced hearing loss, and age-related loss, other indications where hearing loss and tinnitus are prominent features.
About Meniere’s Disease (MD)
MD is diagnosed by episodic vertigo or dizziness, fluctuating hearing loss, and intermittent or constant tinnitus, and is thought to be due to a swelling or inflammation of the inner ear. The auditory symptoms of hearing loss and tinnitus often involve only one ear. Patients are typically diagnosed between 40-65 years of age. In addition, some patients experience aural fullness or pressure that can also contribute to dizziness. As patients age, the hearing loss and/or tinnitus become progressively worse resulting in profound hearing loss or intractable tinnitus. For the definitive diagnosis of MD, the American Academy of Otolaryngology-Head & Neck Surgery guidance requires documentation of ≥30 dB of low frequency hearing loss in at least one ear using PTA. Loss of word recognition or speech discrimination, especially in noisy environments or when tinnitus is present, is common in MD and other forms of hearing loss. MD is currently managed with low salt diets, thiazide diuretics, and oral or locally injected steroids. Unfortunately, this standard of care has not been proven to be effective and is not FDA-approved for the treatment of MD.
SPI-1005 is an investigational drug that contains ebselen, a small molecule that is a new chemical entity, under FDA classification. Ebselen is a selenorganic compound that mimics and induces glutathione peroxidase (GPx) activity and represents a novel class of anti-inflammatory. GPx activity is critical to several cell types and tissues in the inner ear, retina, prefrontal cortex of brain, lung and kidney, and is often reduced during exposures to environmental insults or aging. Loss of GPx activity has been shown to result in sensorineural hearing loss in multiple animal models. SPI-1005 is given orally and is being developed for several neurotologic indications including noise-induced hearing loss and two types of ototoxicity (hearing loss, tinnitus, dizziness or vertigo): due to aminoglycoside antibiotics (such as tobramycin) and due to platinum-based chemotherapy. To our knowledge, SPI-1005 is the only neurotologic drug currently in Phase 3 testing in the US, Europe, or Asia, that has demonstrated clinically relevant improvements in sensorineural hearing loss and tinnitus.
About Sound Pharmaceuticals
A privately held biotechnology company is testing SPI-1005 under four other active Investigational New Drug Applications involving several neurotologic indications, including an ongoing Phase 2 clinical trial in Cystic Fibrosis patients receiving IV tobramycin for the treatment of pulmonary exacerbation. Details of the SPI-1005 clinical trials can be viewed online at www.clinicaltrials.gov, or by visiting www.soundpharma.com.