SAN DIEGO, CALIFORNIA — Otonomy, Inc., a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology, announced positive top-line results from the Phase 1/2 clinical trial of OTO-313 in patients with persistent tinnitus of at least moderate severity.
The exploratory efficacy cohort of the trial included 31 evaluable patients randomized to a single intratympanic injection of OTO-313 or placebo (1:1 randomization) and then followed for eight weeks. Patients reported the severity of their tinnitus symptoms using the Tinnitus Functional Index (TFI), a clinically-validated instrument, and by the daily reporting of their tinnitus loudness and annoyance.
“The trial achieved its objectives by demonstrating a positive clinical signal for OTO-313 based on a TFI responder analysis, with a favorable safety profile.”
Given these results, Otonomy intends to advance OTO-313 into full Phase 2 development which may include evaluation of a higher dose and/or retreatment with OTO-313.
Top-line results for the Phase 1/2 trial were as follows:
- 43% of OTO-313 patients were responders at both Day 29 and Day 57 compared to 13% of placebo patients. A responder is a patient whose TFI score decreases by 13-points or more from their baseline score, a change considered clinically meaningful based on the TFI instrument validation.
- For patients who were responders at both Day 29 and Day 57, OTO-313 demonstrated a higher responder rate than placebo at all TFI improvement levels considered clinically meaningful (TFI reduction ≥ 13, 15, 20, 25, and 30 points). The difference in responder rate between OTO-313 and placebo was statistically significant on post hoc analysis (p-value < 0.05) for TFI reductions ≥ 13, 15, and 20 points.
- OTO-313 patients who were responders at both Day 29 and Day 57 reported improvements in both tinnitus loudness and annoyance levels based on daily diaries and also reported improvement in the Patient Global Impression of Change (PGIC), a general assessment of tinnitus status. There was a very strong relationship demonstrated between the improvement in TFI score reported by these OTO-313 responders and their improvement in tinnitus loudness and annoyance levels as well as PGIC based on the calculated correlation coefficients of ≥ 0.8 for these endpoints.
- A single intratympanic injection of OTO-313 was well-tolerated with lower incidence of adverse events than the placebo group.
“We are excited to announce these positive clinical results for OTO-313 and to advance this potential treatment for patients suffering from the high burden of persistent tinnitus,” said David A. Weber, Ph.D., president and CEO of Otonomy.
“This is also a great start to our three planned clinical trial readouts with results for our OTO-413 Phase 1/2 trial expected in the fourth quarter of 2020 and results from the Phase 3 trial of OTIVIDEX® in Ménière’s disease expected in the first quarter of 2021.”
–David A. Weber, Ph.D., Otonomy President & CEO
“Tinnitus is a common problem that affects millions of people around the world. A significant proportion of patients experience moderate to severe tinnitus, which can negatively impact sleep and relaxation, disrupt the ability to focus at work and at home, create feelings of distress and anxiety, and lower overall quality of life,” said Kenneth Maxwell, M.D., a Neurotologist at Piedmont Ear Nose & Throat Associates in Winston-Salem, North Carolina and an investigator in the OTO-313 Phase 1/2 trial.
“Unfortunately, there are no FDA approved drug treatments for tinnitus and existing approaches rely on coping strategies. Therefore, I am very encouraged by the treatment response observed with OTO-313 in this trial as well as the consistency of the improvement for OTO-313 responders across all four tinnitus endpoints examined in this trial, and I look forward to participating in future clinical studies.”
OTO-313 is a sustained-exposure formulation of the potent and selective N-Methyl-D-Aspartate (NMDA) receptor antagonist gacyclidine providing localized drug administration to the inner ear. We believe that gacyclidine can reduce the severity of tinnitus symptoms following cochlear injury by decreasing the over-activation of damaged auditory nerve fibers in the cochlea and their connections. The therapeutic potential of gacyclidine for tinnitus has been demonstrated in preclinical models and several pilot clinical studies. OTO-313 utilizes a novel, patent-protected formulation technology to provide several weeks of gacyclidine drug exposure in the inner ear compartment following a single intratympanic injection.
Otonomy is a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology. The company pioneered the application of drug delivery technology to the ear in order to develop products that achieve sustained drug exposure from a single local administration. This approach is covered by a broad patent estate and is being utilized to develop a pipeline of products addressing important unmet medical needs including Ménière’s disease, hearing loss, and tinnitus.