Sound Pharmaceuticals has announced positive results from its Phase 3 clinical trial (STOPMD-3) of SPI-1005, a novel anti-inflammatory compound (ebselen), for the treatment of Meniere's Disease. The trial met its co-primary endpoints, demonstrating significant improvements in both hearing loss and speech discrimination.
Meniere's disease (MD) is an inner ear disorder characterized by fluctuating hearing loss, tinnitus, and episodic vertigo or dizziness. Currently, there are no FDA-approved medical treatments specifically for MD, nor for the associated symptoms of hearing loss, tinnitus, vertigo, or dizziness. SPI-1005, an oral capsule containing 200 mg of ebselen, has previously shown promise in Phase 2 clinical trials across various hearing loss and tinnitus indications, including MD.
The STOPMD-3 trial enrolled 221 adult subjects with a confirmed diagnosis of MD and active symptoms. Participants were randomized into a double-blind, placebo-controlled trial, receiving either SPI-1005 (400 mg twice daily) or a placebo for 28 days, with monthly follow-up assessments of auditory and vestibular function over 84 days. Compliant patients were then eligible to enter an open-label extension (OLE) phase, continuing SPI-1005 treatment for up to 12 months, with auditory and vestibular function reassessed every 3 months.
Key Findings from the Clinical Trial
Both intent-to-treat and per-protocol analyses of the randomized controlled trial (RCT) revealed that the SPI-1005 group experienced higher rates of improvement in low-frequency hearing loss (≥10 dB gain at one low frequency from baseline) as measured by pure-tone audiometry (LFPTA) and speech discrimination (≥4-word increase from baseline) using the words-in-noise (WIN) test compared to the placebo group at days 28, 56, and 84 of follow-up.
On day 84, the SPI-1005 group exhibited a statistically significant rate of LFPTA improvement over the placebo group (57.9% vs 36.5%, representing a 58.6% increase over placebo, p-value=0.0037). When the LFPTA criteria were made more stringent, requiring a ≥10 dB gain at two adjacent low frequencies from baseline, the SPI-1005 group showed a significant rate of improvement of 204.4% over placebo (41.1% vs 13.5%, p-value <0.0001). Additionally, on day 84, the SPI-1005 group demonstrated a significant rate of WIN improvement of 54.4% over placebo (42.1% vs. 27.1%, p=0.0336).
Sustained Improvements in Open-Label Extension
During the open-label extension (OLE), responder rates for both LFPTA and WIN continued to improve. Furthermore, patient-reported outcome measures for tinnitus, vertigo, aural fullness, and dizziness severity all showed significant improvements from baseline (≥30% on average, p-value <0.001).
Implications for Meniere's Disease Treatment
"We would like to thank all of our investigators and study participants for contributing to this pivotal Phase 3 trial success involving SPI-1005," stated Jonathan Kil, MD, CEO of Sound Pharmaceuticals. The full RCT/OLE data analysis, along with additional post-hoc analyses, will be presented at the Association for Research in Otolaryngology Midwinter Meeting in Orlando, FL, from February 22-26, 2025.
These results suggest that SPI-1005 could represent a significant advancement in the treatment of Meniere's disease, addressing both hearing loss and speech discrimination deficits, which are major challenges for patients with this condition. Currently, Meniere's disease is often managed with low-salt diets, thiazide diuretics, and oral or locally injected steroids, but these approaches are not consistently effective and lack FDA approval for this specific indication. SPI-1005 offers a potential targeted therapy to improve the lives of individuals affected by Meniere's disease.
