November 13, 2012 – Auris Medical announced today positive results from a phase IIb clinical trial with AM-111, its investigational drug for the intratympanic (i.t.) treatment of acute sensorineural hearing loss (ASNHL). The study
demonstrated that the treatment was well tolerated and showed a statistically significant and clinically
relevant treatment effect.
The double-blind, randomized, placebo-controlled phase IIb study with AM-111 was conducted in Germany,
Poland and the Czech Republic, involving more than 30 sites. A total of 210 patients suffering from acute
acoustic trauma or sudden deafness were enrolled within the first 48 hours following the incident. Their
hearing loss, measured against a reference value, had to be at least 30 dB at the average of 3 contiguous
audiometric test frequencies. Study participants received one single dose of either AM-111 at 0.4 or 2
mg/ml or placebo by way of i.t. injection and were followed for 90 days. In case of insufficient hearing re-
covery by Day 7, they were given the option of receiving oral prednisolone as a reserve therapy.
Preliminary results from the phase IIb study show that the local treatment with AM-111 was well tolerated.
In addition, the study demonstrated a substantial improvement in hearing threshold and speech discrimina-
tion score. In subjects with severe to profound hearing loss who were treated with AM-111 0.4 mg/mL, the
primary study endpoint, absolute hearing improvement in the 3 most affected contiguous test frequencies
from baseline to Day 7, was met (p < 0.02, compared with placebo). The outcome was confirmed by the co-
primary endpoint “% of hearing loss recovered at Day 7” (p < 0.03); the odds ratio for complete hearing
recovery was > 2.2. Importantly, the improvement in the speech discrimination score from baseline to Day 7
showed also a statistically significant difference between AM-111 and placebo treated study subjects (p <
0.02). The differences in hearing and speech discrimination recovery between treatment groups appeared as
early as on Day 3 and were clinically relevant. Further information on the clinical trial and detailed out-
comes shall be presented in a scientific journal.
“The cell penetrating peptide AM-111 represents a novel approach to treating ASNHL“, stated Professor
Markus Suckfüll, Munich (Germany), coordinating investigator of the study. “The clear and clinically mean-
ingful improvements observed with AM-111 in the treatment of severe to profound hearing loss demon-
strate that effective otoprotection is feasible, and they appear very promising. The inclusion of a placebo
arm to control for the effects of spontaneous recovery lends particular credibility to the results and will
provide also a wealth of important new information for future hearing research.” Thomas Meyer, Auris
Medical’s founder and Managing Director, commented: “We are very pleased with the positive results from
the phase IIb trial with AM-111, which were achieved under challenging clinical conditions. The outcomes
are in line with the positive results from preclinical studies conducted in various ASHNL conditions, which
had demonstrated the strong otoprotective effects of the peptide.” In a next step, Auris Medical is planning
to discuss the phase IIb results and further clinical development with AM-111 with regulatory agencies.
About acute sensorineural hearing loss
Acute sensorineural hearing loss may be the consequence of various insults to the cochlea. It may result e.g.
from overexposure to noise, bacterial or viral infections, inflammation, vascular compromise, or a variety of
other factors. In ASNHL, sensorineural structures of the inner ear – inner and outer hair cells, neurons – are
damaged, as well as other structures such as supporting cells or vascular tissues. The common observation is a temporary increase in hearing thresholds, i.e. hearing loss. Thanks to cellular defences and intrinsic re-
pair mechanisms, a certain amount of such hearing loss is frequently recovered in the subsequent days and
weeks. The remaining hearing loss however is irreversible. ASNHL may be accompanied by other disorders of
the inner ear such as dizziness or tinnitus.
When ASNHL develops into permanent hearing loss, it may have chronically debilitating consequences.
Hearing loss may have serious impacts on professional and personal lives, e.g. through avoidance or with-
drawal from social situations, reduced alertness and increased risk to personal safety, impaired memory and
ability to learn new tasks, or reduced job performance and earning power. To date, there exists no treatment
for ASNHL with proven efficacy.
AM-111 is a cell-permeable peptide that selectively blocks JNK MAPK mediated apoptosis of stress injured
hair cells and neurons in the cochlea. Major cochlear stress incidents that may result in irreversible hearing
loss include exposure to excessive noise, disturbances of the blood supply, viral or bacterial infections, and
exposure to certain ototoxic substances. When administered within a therapeutic time window after the
incident, AM-111 can effectively protect cochlear hair cells and neurons that would otherwise undergo
apoptosis and be lost forever. AM-111’s otoprotective properties have been extensively tested and con-
firmed in various animal models so far, including acute acoustic trauma, acute labyrinthitis, surgery trauma,
aminoglycoside ototoxicity, semicircular canal injury in otitis media and cochlear ischemia. AM-111 has
been granted orphan drug status in both the European Union and the USA for the treatment of acute sen-
sorineural hearing loss. The active substance of AM-111 has been in-licensed by Auris Medical from Swiss
biotechnology company Xigen S.A.
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 permanently suffering from severe hearing loss and tinnitus. Truly effective and
safe treatments for these disorders are still lacking. 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).
Dr. Thomas Meyer, Managing Director, telephone +41 61 201 13 50, firstname.lastname@example.org