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Auris Medical reporting results of phase I/II clinical trial with AM-101

Auris Medical reporting results of phase I/II clinical trial with AM-101

Editor: The folks at Auris Medical are developing drugs to treat ear-related conditions. Here’s their notice on recent clinical trials of their tinnitus drug.

Auris Medical reported the results of the first clinical trial with AM-101, its investigational drug for the treatment of inner ear tinnitus. The double blind, randomised clinical trial with placebo control involved four study sites in Germany and had the evaluation of AM-101’s safety as primary objective. As a secondary objective, the potential efficacy of AM-101 was evaluated. The study results show that intratympanically injected AM-101 was well tolerated by study participants, and provided first indications of therapeutic efficacy.

The first clinical evaluation of AM-101, an investigational medicinal product under development by Auris Medical for the treatment of inner ear tinnitus, was conducted from March 2007 to March 2008 in a phase I/II study in Germany. A total of 24 patients suffering from persisting moderate to severe tinnitus following acute noise trauma or sudden deafness were enrolled at 4 study centres (3 clinics of the German Bundeswehr and 1 private ear, nose and throat practice). Their tinnitus had been refractory to a first-line corticoid treatment prior to study inclusion, and was not older than 3 months (i.e. still at an acute stage). Study participants were randomized to receive either AM-101 or placebo in a single dose intratympanic injection, whereby a total of 4 dose concentrations were tested under a dose escalation scheme.

Follow-up visits were performed 7, 30 and 60 days after treatment administration. The primary objective of the study was to evaluate the safety of AM-101 delivered by intratympanic injection. Secondary objectives were a preliminary evaluation of the potential therapeutic benefit of AM-101 in the treatment of acute inner ear tinnitus as well as the determination of the systemic exposure from local drug administration. The study’s lead investigator was Professor Heinz Maier, Head of the Otorhinolaryngology and Head and Neck Surgery Department of the Bundeswehr clinic of Ulm (Germany).

At baseline, i.e. before administration of AM-101, study participants on average had had tinnitus for 62 days. In 19 cases, tinnitus had been provoked by acute acoustic trauma, in 5 cases it had been related to sudden deafness. A slight majority of patients suffered from bilateral tinnitus (13 out 24), in which case only the worse affected ear was treated. The average audiogram was downward sloping with a maximum hearing loss at 6 kHz.

Overall, AM-101 was well tolerated by study participants, irrespective of the administered dose. Adverse events occurred in only few patients and were either unrelated or considered unlikely related to the phar-maceutical treatment. AM-101 and its primary metabolite could be found in plasma samples obtained in the first hours following treatment in traces only, which confirmed the favourable safety profile of intra-tympanic injection. This minimally invasive procedure allows for a highly site specific treatment with low doses and only minimal systemic exposure.

In terms of efficacy, the clinical trial provided first indications for the potential efficacy of AM-101 in the treatment of inner ear tinnitus. The clinical data suggest that AM-101 has a positive effect on the perceived loudness of tinnitus as well as on its maskability; in addition, a positive trend was observed in the overall

Auris Medical AG, Aeschenvorstadt 37, CH-4051 Basel, www.aurismedical.com Laboratoires Auris SAS, CEEI Cap Alpha, Avenue de l’Europe, FR-34940 Montpellier Cedex 09 Auris Medical Inc., 444 North Michigan Avenue, Chicago, IL 60611, USA

tinnitus handicap as measured by the TBF-12 questionnaire. Further details of the clinical trial and its out-comes shall be published later in a scientific journal.

Thomas Meyer, Auris Medical’s founder and Managing Director, commented: “We are very pleased with the positive results from this first clinical evaluation of AM-101. The trial not only confirmed the presumed good safety profile following local application, but also provided encouraging early indications of potential efficacy.” He added that the successful conclusion of the study represented an important milestone for Auris Medical and the development of a treatment for inner ear tinnitus, an area of great unmet medical need. In a next step, Auris Medical is planning to test AM-101’s efficacy in a phase IIb clinical trial with a substantially larger number of participants.

About AM-101

AM-101 contains a small molecule that selectively blocks NMDA receptors. Based on research conducted at the INSERM Institute for Neurosciences of Montpellier, France, NMDA receptors in the cochlea can provoke aberrant activity of the auditory nerve which is perceived as tinnitus. NMDA receptors do not seem to be involved in fast excitatory neurotransmission which is essential for hearing, but may be activated following some excitotoxic incident such as noise trauma or sudden deafness. It had been demonstrated in behav-ioural and electrophysiological models that local administration of the NMDA antagonist AM-101 to ani-mals suffering from tinnitus effectively suppressed the perception of the “phantom sound”. The develop-ment of AM-101 was supported by Oséo ANVAR, the French agency for the financing and support of small and mid-sized business enterprises.

About Auris Medical

Auris Medical is a Swiss-French 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 and / or tinnitus, still lacking truly effective 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).