Hear ye, hear ye

ZUG, Switzerland—Mid-March saw Auris Medical Holding AG, a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in neurotology and central nervous system disorders, announce the publication of an article that presents and discusses in detail the outcomes from the HEALOS Phase 3 trial with AM-111, Auris Medical’s investigational treatment for acute inner ear hearing loss.

The peer-reviewed article “Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness - A Double-Blind, Randomized, Placebo-Controlled Phase 3 Study” was published in Otology & Neurotology, one of the leading journals in the field of scientific and clinical inner ear research.

While the HEALOS trial did not meet the primary efficacy endpoint in the overall study population, post-hoc analyses revealed a statistically significant hearing improvement with AM-111 from baseline to day 28 in the subpopulation of patients with profound hearing loss (n=98). The AM-111 0.4 mg/mL treatment group showed a mean improvement of 42.7 dB vs. 26.8 dB in the placebo group (p=0.0176). AM-111 was well tolerated, and the primary safety endpoint was met.

“The HEALOS trial demonstrated that effective hearing protection is possible with a drug-based approach even in the case of profound acute hearing loss, a condition with very poor prognosis for recovery and high risk for life-long auditory and cognitive disability,” commented Dr. Hinrich Staecker,  a professor in the Department of Otolaryngology Head and Neck Surgery at the University of Kansas Medical Center and lead author on the publication. “In the trial, treatment with a single dose of AM-111 resulted in a clinically meaningful hearing recovery and a marked reduction in the risk of no improvement. These outcomes are very promising, as there are still no effective drug treatments available to protect hearing.”

The HEALOS trial was conducted in several European and Asian countries as a randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and tolerability of AM-111. It enrolled 256 patients suffering from severe to profound sudden deafness within 72 hours from onset. Patients were randomized in a 1:1:1 ratio to receive a single dose of either AM-111 0.4 mg/mL, AM-111 0.8 mg/m or placebo, administered into the middle ear.

AM-111 is being developed in a biocompatible gel formulation for the treatment of sudden sensorineural hearing loss with a single-dose administration into the middle ear. Its active substance is brimapitide (also known as D-JNKI-1, D-stereoisomer of c-Jun N-terminal kinase inhibitor 1), a cell-penetrating peptide which inhibits the JNK stress kinase. JNK is activated following various types of cochlear insults (stress) that cause acute inner ear hearing loss and plays a key role in apoptosis of sensory cells as well as in inflammatory responses. By blocking JNK, AM-111 theoretically protects stress-injured cochlear cells and helps to prevent or reduce chronic hearing loss.

AM-111’s otoprotective effects have been demonstrated in various animal models of cochlear stress, including acute acoustic trauma, acute labyrinthitis (inflammation), drug ototoxicity (aminoglycosides), bacterial infection, cochlear ischemia and cochlear implantation trauma. AM-111 has Orphan Drug Designation from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency, and it was granted Fast Track status by the FDA.