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Sound Pharmaceuticals announces positive topline results from the SPI-1005 Phase 2b Meniere’s Disease clinical trial

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SEATTLE — SPI-1005 hits pre-specified endpoints resulting in a significant improvement in hearing loss of 65% and 95% relative to placebo

Sound Pharmaceuticals today announced positive top-line results from a randomized, double-blind, placebo-controlled, multi-center Phase 2b study in Meniere’s Disease (MD). The study consented 149 adult patients with active MD, including a hearing loss at baseline of >30 dB in one of three low frequencies, to receive either placebo, 200, or 400 mg SPI-1005 by mouth, twice daily for 28 days, with follow-up assessments at 4 and 8 weeks after the start of treatment. The pre-specified audiometric endpoints were to determine if SPI-1005 could improve hearing sensitivity or thresholds in dB by a clinically relevant difference vs placebo.

In the trial, clinically relevant improvements in hearing loss (≥10 dB gain from baseline at one low frequency) using pure-tone audiometry (PTA) were significantly higher in the 400 mg dose group vs placebo (61% vs 37%, p<0.023), a relative improvement of 65% over placebo at 8 weeks. Clinically relevant improvements in word recognition (≥10% increase in word recognition from baseline) using the words-in-noise test (WINT) also showed higher responses when compared to placebo (75% vs 56%, p<0.060), a relative improvement of 34% over placebo at 8 weeks. Secondary efficacy endpoints were also tested using stricter responder criteria involving PTA and WINT. Using stricter PTA criteria (≥10 dB gain from baseline at two adjacent low frequencies), the 400 mg dose group showed higher relative response rates (39% vs 20%, p<0.044), a 95% improvement over placebo. Using stricter WINT criteria (≥4 words improvement from baseline), the 400 mg dose group showed higher relative response rates (60% vs 34%, p<0.017), a 76% improvement over placebo. Results from the Intent-to-Treat (ITT) analysis showed that SPI-1005 was well-tolerated in the 124 patients that received at least one oral dose of study drug during the 28-day dosing period. No serious adverse events occurred, and the majority of adverse events were mild to moderate, and consistent with those observed in prior studies. A more detailed presentation of the ITT and Per-Protocol analyses will occur at a scientific meeting later this year.

“This clinical trial indicates that SPI-1005 may have the potential to significantly improve the loss of hearing and loss of word recognition in Meniere’s, a complex and chronic inner ear disease,” said Jonathan Kil, MD, Co-Founder and CEO.

About the Phase 2b trial

Enrollment occurred at 14 sites across the US between Sept 2017 and March 2019 and involved 149 consented adults (22-75 yo). Eligible patients with active Meniere’s Disease (MD) symptoms, including a ≥30 dB hearing loss at baseline in one of three tested low frequencies (250, 500 or 1000 Hz), were randomized (1:1:1) to either placebo or one of two oral doses of SPI-1005 (200 or 400 mg, twice daily). Each study arm (n=41-42 adults) received 28 days of treatment and had follow-up assessments at 4 and 8 weeks after the start of treatment. Clinically relevant improvements in sensorineural hearing loss were determined using PTA and WINT, two validated measures of hearing sensitivity and specificity that are administered by an audiologist; patient-reported quality-of-life outcomes of tinnitus were self-assessed using the Tinnitus Functional Index (TFI); and patient-reported outcomes of vertigo were self-assessed using the Vertigo Symptoms Scale (VSS). The improvement in PTA/WINT and TFI/VSS scores were compared between SPI-1005 dose groups and the placebo group.

The average age in the ITT population was 54.5 years (66 females and 58 males) and some study participants had been diagnosed with MD over 20 years before study enrollment. In the ITT analysis, statistically significant improvements were not observed in low frequency hearing loss and word recognition at 4 weeks when compared to placebo. Therefore, this Phase 2b study provides important data for the design of our future Phase 3 clinical trials. The results suggest both an effective dose of SPI-1005 (400 mg twice daily) and period of follow-up (8 weeks from the start of study drug) to be used as our primary endpoint in future pivotal studies where an active MD population is treated. The continued auditory improvement in the 400 mg dose group (from 47% at 4 weeks to 61% at 8 weeks) suggests the potential for a durable neurotologic effect of SPI-1005 treatment.
“We are very excited by the magnitude of the positive results of this trial in this diverse Meniere’s disease population,” said Dr. Paul Lambert, Lead Principal Investigator of the Phase 2b study. Dr. Lambert is a world renowned neurotologist, past President of the American Neurotologic Society, and the Chairman of the Dept. of Otolaryngology-Head & Neck Surgery at the Medical University of South Carolina in Charleston, SC.

About Meniere’s Disease (MD)

MD is diagnosed by episodic vertigo, 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 (low frequencies below 2000 Hz) and tinnitus (roaring/ringing) often involve one ear. MD patients are typically diagnosed between 40-65 years of age. As patients age, the hearing loss and/or tinnitus become progressively worse. For the definitive diagnosis of MD, new 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. The upper limit of normal hearing sensitivity is 20 dB, and every 10 dB loss of hearing is considered clinically relevant. Loss of word recognition is a common complaint in MD, especially when tinnitus is also present. Currently, there are no FDA approved drug treatments for MD, or any other inner ear disease. MD is managed with low salt diets, thiazide diuretics, and oral or locally injected steroids. Unfortunately, this type of medical management or standard of care has not been proven to be effective.

About SPI-1005

SPI-1005 is an investigational new drug that contains ebselen, a small molecule that is a new chemical entity or NCE 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, brain, lung and kidney, and is often reduced during exposures to environmental insults. 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 tested in several neurotologic indications including noise induced hearing loss and tinnitus, and two types of ototoxicity (hearing loss, tinnitus, dizziness or vertigo), due to aminoglycoside antibiotics (such as tobramycin), and due to platinum-based chemotherapy. In earlier clinical trials, SPI-1005 demonstrated strong proof-of-concept data supporting the potential treatment in preventing and treating noise induced hearing loss and Meniere’s disease.

About Sound Pharmaceuticals

A privately held biotechnology company is testing SPI-1005 under four 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. The company is also studying bipolar disorder in collaboration with the University of Oxford, in a proof-of-concept Phase 2 clinical trial where the novel anti-inflammatory and neuroprotective properties of SPI-1005 are being tested in active hypomania. This study has recently completed enrollment and will disclose top-line data later this summer.

Details of the SPI-1005 clinical trials can be viewed online at www.clinicaltrials.gov.

Sound Pharmaceuticals advances Phase 2 hearing loss clinical trial in Cystic Fibrosis

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Seattle, WA and Charleston, S.C.

Sound Pharmaceuticals (SPI) is pleased to announce that first-patient-in has been achieved in the STOP Ototoxicity Phase 2 clinical trial. This novel interventional study with SPI-1005 is aimed to prevent and treat ototoxicity in Cystic Fibrosis (CF) patients undergoing intravenous (IV) tobramycin for the treatment of acute pulmonary exacerbation.

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Sound Pharmaceuticals to Present Preliminary Data on Ototoxicity Study

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Denver, CO

Sound Pharmaceuticals (SPI) will present data on the incidence and severity of ototoxicity in cystic fibrosis (CF) patients who received tobramycin for the treatment of acute pulmonary exacerbations.

The presentation, which was accepted as a late-breaking abstract, will be given at the upcoming North American Cystic Fibrosis Conference (NACFC), taking place Oct. 18-20 in Denver.

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University of Oxford and Sound Pharmaceuticals begin Phase 2 clinical trial on novel treatment for bipolar disorder

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Seattle, WA and Oxford, England

The University of Oxford and Sound Pharmaceuticals (SPI), are pleased to announce the initiation of a Phase 2 clinical trial of SPI-1005 for the treatment of patients with bipolar disorder. SPI-1005 is an oral drug that contains ebselen, which mimics and induces the activity of Glutathione Peroxidase (GPx) in the inner ear and brain. SPI-1005 is under clinical investigation in several neurotologic diseases where GPx activity is reduced including sensorineural hearing loss, ototoxicity/neurotoxicity, and Meniere’s disease. In addition to these neurotologic diseases, GPx activity is thought to be diminished in several neuropsychiatric disorders including bipolar, schizophrenia and autism. Bipolar disorder involves both mania and depression, and has been difficult to treat chronically. Lithium, a mainstay of bipolar treatment has significant dose-limiting side effects. Read More

Sound Pharmaceuticals announces positive Phase 1b results and the start of a Phase 2b clinical trial in Meniere’s Disease

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Seattle, WA

Sound Pharmaceuticals (SPI) is pleased to announce positive topline results from its recently completed Phase 1b SPI-1005-151 clinical trial involving Meniere’s Disease (MD). SPI-1005 is an investigational new drug that mimics and induces glutathione peroxidase activity, and has demonstrated strong proof-of-concept in preventing sensorineural hearing loss. MD is diagnosed by episodic vertigo, fluctuating hearing loss, and intermittent or constant tinnitus, and is thought to be due to a swelling or inflammation of the inner ear. Currently, there are no FDA approved drug treatments for MD, or any other inner ear disease. Many with MD are managed with low salt diets, thiazide diuretics, and oral or locally injected steroids, although these treatments have not proven to be effective. Read More

Enrollment Underway in CF Clinical Trial for Ear Toxicity Caused by Antibiotics

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Seattle, WA

The first study of cystic fibrosis (CF) patients who received antibiotics that caused inner ear disease or ototoxicity is enrolling participants, according to Sound Pharmaceuticals.

The Phase 1b STOP Ototoxicity study (NCT02819856) is led by Dr. Patrick Flume, MD, professor of medicine and pediatrics at the Medical University of South Carolina in Charleston, where the study is taking place. He is an expert in pulmonary disease and cystic fibrosis. Read More

Sound Pharmaceuticals completes enrollment on Meniere’s Disease clinical trial

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Seattle, WA

Sound Pharmaceuticals (SPI) is pleased to announce that it has completed enrollment on its first Meniere’s Disease (MD) clinical trial. MD is a neurotologic disease that involves episodic vertigo, fluctuating sensorineural hearing loss, and intermittent or constant tinnitus, and is thought to be due to a swelling or inflammation of the inner ear. Patients with MD may also complain of aural fullness or pressure, and in extreme cases, may require surgery to decompress the inner ear. SPI-1005, an investigational new drug that mimics and induces Glutathione Peroxidase (GPx), has been shown to reduce the swelling or edema of the inner ear in animal studies involving acoustic trauma. Read More

Sound Pharmaceuticals announces $1.6 Million Award from Cystic Fibrosis Foundation Therapeutics to prevent and treat the hearing loss and tinnitus associated with antibiotic use

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Seattle, WA

Sound Pharmaceuticals, Inc., (SPI) is pleased to announce that it has been awarded up to $1.6M from Cystic Fibrosis Foundation Therapeutics Inc. (CFFT), the non-profit drug discovery and development affiliate of the Cystic Fibrosis Foundation. The CFFT development award will support the initial testing of SPI-1005 in people with CF who are receiving tobramycin for the treatment of acute pulmonary exacerbations or lung infections. A leading side effect of tobramycin involves damage to the inner ear and is called ototoxicity. The Phase 1b STOP Ototoxicity clinical trial will examine the incidence and severity of hearing loss, tinnitus, dizziness or vertigo due to IV tobramycin treatment. SPI-1005 is a novel oral drug that is being developed to reduce the incidence and severity of sensorineural hearing loss and tinnitus in several disease states including ototoxicity, noise and Meniere’s disease.
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