The double-blind, randomized, placebo-controlled, parallel-dose phase IIb study with AM-101 was con- ducted in Germany, Belgium, Poland and the Netherlands, involving almost 30 sites. A total of 248 patients suffering from persistent acute inner ear tinnitus were randomized to receive 3 intratympanic injections of either AM-101 at 0.27 or 0.81 mg/ml or placebo over 3 consecutive days. Their tinnitus had to be triggered by acute acoustic trauma, sudden deafness or otitis media and to be no older than 3 months. The clinical trial evaluated the safety and local tolerance of AM-101 and various efficacy outcomes. Study participants were monitored over 90 days.
Preliminary results from the phase IIb study show that the local treatment with AM-101 was very well tol- erated, and in particular that it had no negative impact on hearing. In addition, the study demonstrated a dose-dependent improvement in various measures of tinnitus impairment, disability and handicap. Patients suffering from acute tinnitus with established cochlear origin who received AM-101 at 0.81 mg/ml showed a statistically significant reduction in tinnitus loudness, sleep impact and the THI-12 questionnaire score (p <0.05 or <0.01). Further information on the clinical trial and detailed outcomes shall be published in a sci- entific journal.
“We are very pleased with the positive results from this important clinical trial with AM-101,” stated Tho- mas Meyer, Auris Medical’s founder and Managing Director. “The study confirmed the excellent safety pro- file of the treatment and established proof of concept for efficacy in humans.” He added that the successful conclusion of the study represented a great step forward in the development of a treatment for inner ear tinnitus, an area of great unmet medical need. Auris Medical is planning now to discuss the results from the phase IIb trial with regulatory agencies and to prepare the next development steps for AM-101.
About acute inner ear tinnitus
Tinnitus, the perception of sound without external acoustic stimulation, is a symptom common to various ear or other diseases. Inner ear tinnitus may be provoked by various injuries to the cochlea, the organ of hearing, such as overexposure to noise or disruptions in its blood supply. It may be short and just transitory; however, it may also become permanent. Tinnitus of less than three months of duration is considered acute, while tinnitus that is older than one year is considered chronic.
Inner ear tinnitus may be only a slight nuisance, but often it has a serious impact on the ability to sleep, relax, or concentrate, or it may lead to tiredness, irritation, nervousness, despair, frustration, or even depres- sion. As of today, there exists neither a universal standard of care for acute inner ear tinnitus, nor a truly proven, effective treatment method.
About AM-101
AM-101 contains a small molecule that selectively blocks N-methyl-D-aspartate (NMDA) receptors. Emerg- ing evidence suggests that NMDA receptors in the cochlea play a major role in the occurrence of tinnitus following inner ear excitotoxicity, which is characterized by excessive synaptic release of glutamate, the principal neurotransmitter in the auditory system. Cochlear excitotoxicity may be triggered by, for example, exposure to excessive noise, disturbances in inner ear blood supply (anoxia/ischemia), barotrauma, migration of pathogens from the inflamed middle ear into the inner ear, noise / vibration trauma resulting from mid- dle ear surgery, or the administration of certain ototoxic drugs. It has been hypothesized that the upregula- tion of NMDA receptors induced by cochlear excitotoxicity is responsible for abnormal spontaneous “firing” of auditory nerve fibres, which is perceived as tinnitus.
The development of AM-101 is based on research conducted at the INSERM Institute for Neurosciences of Montpellier, France, and has been supported by Oséo ANVAR, the French agency for the financing and sup- port of small and mid-sized business enterprises. The clinical development of AM-101 was initiated by Auris Medical in 2007. A phase II study (TACCT1) is currently ongoing in the USA. Patents have been granted in more than 30 countries worldwide to date.
About Auris Medical
Auris Medical is a Swiss biotechnology company developing specific pharmaceutical compounds for the prevention or treatment of inner ear disorders, an area of great unmet medical need. Around the world, many million people are suffering permanently from severe hearing loss or tinnitus, still lacking truly effec- tive and safe treatments for their disorders. Auris Medical is currently focusing on the development of treatments for acute inner ear tinnitus (AM-101) and for acute sensorineural hearing loss (AM-111).
Contact:
Dr. Thomas Meyer, Managing Director, telephone +41 61 201 13 50, tm@aurismedical.com
