- Trial outcomes show positive safety profile of Keyzilen® for chronic intermittent use
- Exploratory efficacy results support therapeutic concept of early tinnitus treatment
Zug, Switzerland, April 24, 2017 - Auris Medical Holding AG (NASDAQ: EARS), a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in otolaryngology, today announced key results from AMPACT2 (AM-101 in the Post-Acute Treatment of Peripheral Tinnitus 2), the open-label extension study of the Phase 3 TACTT3 clinical trial. The study confirms the long-term safety of Keyzilen® and further supports early treatment from onset of inner ear tinnitus.
"We are very pleased that AMPACT2 provides further evidence of good tolerance and safety for Keyzilen® and shows this, for the first time, also for chronic intermittent use," commented Thomas Meyer, Auris Medical's founder, Chairman and Chief Executive Officer. "In addition, the exploratory efficacy data from AMPACT2 lend further support to our therapeutic approach of treating tinnitus early, while the symptom is still of peripheral rather than central character." In 2015, an interim analysis of data from patients with post-acute tinnitus in TACTT3 provided first suggestions that improvements were more pronounced the earlier they had enrolled in the trial.
AMPACT2 is one of two open-label extension studies with Keyzilen® that were conducted at the request of the US Food and Drug Administration (FDA) to generate safety data from chronic intermittent use of Keyzilen® for up to 12 months. Participants who completed the TACTT3 trial were offered the option to roll over into AMPACT2, while still blinded to the treatment allocation. Patients were given the choice to receive up to three treatment cycles with each cycle comprising three intratympanic administrations of Keyzilen®, followed by a treatment-free observation period of 12 weeks. Of the approximately 660 patients enrolled in the TACTT3 trial up to June 2016, 485 patients rolled over into AMPACT2 and provided safety data; 422 of these patients provided exploratory efficacy data. At the time of enrollment into AMPACT2, all patients were in the post-acute stage; approximately half were from Stratum A (originally enrolled in TACTT3 during the acute stage; i.e. up to three months from onset) and the other half were from Stratum B (originally enrolled during the post-acute stage; i.e. between three and 12 months from onset).
The primary safety endpoint of AMPACT2 was the incidence of clinically relevant hearing deterioration five weeks after the start of a treatment cycle. In line with the results from previous trials with Keyzilen®, such incidence was low, amounting to 4-8% with no significant difference between one, two or three treatment cycles. During the course of AMPACT2, the patients' hearing threshold at the average of 4, 6 and 8 kHz was stable. The vast majority of adverse events that were considered related to the study drug or treatment procedure were rated as either mild or moderate in intensity. Seven patients experienced a total of eight non-fatal, serious adverse events, none of which was considered related to the study drug. Confirming previous data, 96-98% of tympanic membranes were already closed at the time of the first follow-up visit.
Exploratory efficacy analyses of AMPACT2 show improvements in the Tinnitus Functional Index (TFI) that were more pronounced for Stratum A patients compared to Stratum B patients. For Stratum A patients, the TFI decreased on average by 7.6 points (95% confidence interval 5.5 to 9.6; baseline of 40.3 points) to the last follow-up visit. For Stratum B patients, the TFI decreased on average by 3.5 points (1.4 to 5.6; baseline of 42.3 points) when enrolled in TACTT3 between three and six months from onset and by 2.5 points (-1.1 to 6.1; baseline of 45.3 points) when enrolled in TACTT3 between six and 12 months from onset.
Auris Medical expects to announce results from AMPACT1, the open-label extension study related to TACTT2, later this quarter. TACTT3 has been extended to recruit an additional 60 patients in each of Stratum A and B, and enrollment is ongoing; top-line results are expected in early 2018. As recruitment for AMPACT2 has completed, the open-label extension is not offered to patients currently enrolling in the extended TACTT3 trial.
About Acute Inner Ear Tinnitus
Tinnitus is the perception of sound without external acoustic stimulation. Tinnitus of the inner ear may be caused by various injuries to the cochlea, the organ of hearing, such as overexposure to noise. Tinnitus that has been present for less than three months is considered acute, while tinnitus that has been present for over three months is considered chronic. Tinnitus of the inner ear often has a serious impact on ability to sleep, relax or concentrate, which may lead to tiredness, irritation, anxiety or depression. There is no universal standard of care for tinnitus of the inner ear and efficacy of a pharmacological treatment for tinnitus of the inner ear has not yet been conclusively demonstrated.
About Keyzilen® (AM-101)
Keyzilen® is a small molecule N-methyl-D-aspartate (NMDA) receptor antagonist formulated in a biocompatible gel and delivered by intratympanic injection. Keyzilen® is in development for treatment of acute tinnitus of the inner ear. Emerging evidence suggests that NMDA receptors in the cochlea play a major role in the occurrence of tinnitus following acute injury to the inner ear; e.g. from exposure to excessive noise, infections, disturbances in inner ear blood supply, or the administration of certain ototoxic drugs. Persistent overexpression of NMDA receptors may lead to pathologic excitation of auditory nerve fibers, which in the brain is perceived as tinnitus. The development of Keyzilen® is based on research conducted at the INSERM Institute for Neurosciences, and patents have been granted in more than 40 countries worldwide so far.
About Auris Medical
Auris Medical is a Swiss biopharmaceutical company dedicated to developing therapeutics that address important unmet medical needs in otolaryngology. The Company is focused on the Phase 3 development of treatments for acute inner ear hearing loss (AM-111) and for acute inner ear tinnitus (Keyzilen®; AM-101) by way of intratympanic administration with biocompatible gel formulations. In addition, Auris Medical is pursuing intranasal betahistine for Meniere's disease and vestibular vertigo (AM-125) as well as early-stage research and development projects. The Company was founded in 2003 and is headquartered in Zug, Switzerland. The shares of Auris Medical Holding AG trade on the NASDAQ Global Market under the symbol "EARS."
This press release may contain statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical fact and may include statements that address future operating, financial or business performance or Auris Medical's strategies or expectations. In some cases, you can identify these statements by forward-looking words such as "may," "might," "will," "should," "expects," "plans," "anticipates," "believes," "estimates," "predicts," "projects," "potential," "outlook" or "continue," and other comparable terminology. Forward-looking statements are based on management's current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to, the timing and conduct of clinical trials of Auris Medical's product candidates, including the likelihood that the TACTT3 clinical trial with Keyzilen® will not meet its endpoints, the acceptability of the data from AMPACT1 and AMPACT2 in support of a potential new drug application to the FDA and other regulators, the clinical utility of Auris Medical's product candidates, the timing or likelihood of regulatory filings and approvals, Auris Medical's intellectual property position and Auris Medical's financial position, including the impact of any future acquisitions, dispositions, partnerships, license transactions or changes to Auris Medical's capital structure, including future securities offerings; the use of proceeds from Auris Medical's recent equity offering and the ability of Auris Medical to finance its operations in the future. These risks and uncertainties also include, but are not limited to, those described under the caption "Risk Factors" in Auris Medical's Annual Report on Form 20-F and future filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date they are made, and Auris Medical does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. All forward-looking statements are qualified in their entirety by this cautionary statement.
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