OTO-104 is a sustained-exposure formulation of the steroid dexamethasone in development for the treatment of patients with Ménière’s disease and cisplatin-induced hearing loss.
Ménière’s Disease Program
Ménière’s disease is a chronic condition characterized by acute vertigo attacks, tinnitus, fluctuating hearing loss and a feeling of aural fullness. Of these symptoms, the vertigo attacks are typically most troubling for patients since they disrupt daily activities and are difficult to anticipate and manage. In general, patients are diagnosed with unilateral Ménière’s disease in middle age and symptoms often continue for decades. Over time, the fluctuating hearing loss becomes permanent in many patients, and a subset of patients will develop symptoms in their second ear. According to the National Institute of Deafness and Other Communication Disorders, there are more than 600,000 patients diagnosed with Ménière’s disease in the United States. There is no known cure for Ménière’s disease and there are currently no FDA-approved drug treatments.
In May 2015, we announced results from a Phase 2b trial evaluating OTO-104 in 154 patients with unilateral Ménière’s disease. The primary endpoint of the trial was reduction in vertigo frequency during Month 3 following treatment compared to a one month baseline period. In the topline analysis, OTO-104 demonstrated a 61% reduction from baseline in vertigo frequency in Month 3 vs. 43% for placebo with a p value of 0.067, which narrowly missed achieving statistical significance. The trial achieved statistical significance (p < 0.05) for multiple prospectively defined secondary vertigo endpoints at multiple time points including the count of Definitive Vertigo Days (DVD) that achieved statistical significance in both Month 3 (p = 0.030) and Month 2 (p = 0.035). Based on these results, and discussions with the FDA during an End-of-Phase 2 meeting, we are conducting two parallel Phase 3 trials in Ménière’s disease using DVD during Month 3 as the primary endpoint. AVERTS-1 (Alleviation of Vertigo Episodes Study) is the Phase 3 trial underway in the United States while an identical second trial called AVERTS-2 is ongoing in the European Union. Results of both Phase 3 trials are expected in the second half of 2017. Patients completing the Phase 3 trials will have the opportunity to enroll in an open label safety study and receive two quarterly doses of OTO-104.
OTO-104 for Ménière’s disease has been granted Fast Track designation by the FDA.
Cisplatin-Induced Hearing Loss Program
Cisplatin and other platinum-based chemotherapeutic agents are routinely used in treating numerous tumor types with approximately 500,000 patients including 2,000 children treated each year in the United States. While use of platinum agents has contributed to improved patient survival, ototoxicity and associated permanent hearing loss is well documented in the clinical literature. In particular, hearing loss has been reported in up to 90% of children and young adults treated with platinum-based agents. This adversely affects speech and language development and has been associated with academic and social difficulties which can have a significant impact on patients and their families. At this time, there is no FDA-approved drug treatment to protect against platinum-based ototoxicity.
Otonomy published a preclinical study titled, “The Sustained-Exposure Dexamethasone Formulation OTO-104 Offers Effective Protection against Cisplatin-Induced Hearing Loss” in the peer-reviewed journal Audiology & Neurotology. This study demonstrated that intratympanic administration of 6% OTO-104 protected against ototoxicity observed following both acute and repeat administration of the chemotherapeutic agent cisplatin. Based on support from this preclinical study, we have initiated a Phase 2 clinical trial evaluating OTO-104 for the prevention of hearing loss in cancer patients undergoing chemotherapy with cisplatin. In January 2017, we announced enrollment of the first patients in this multicenter trial which is designed to assess the feasibility, safety and exploratory efficacy of OTO-104 given by intratympanic administration. The Phase 2 trial is expected to enroll up to 60 subjects at 8-10 leading oncology centers in the United States.
We also plan to assess and prioritize additional opportunities for OTO-104 including other balance disorders, acute onset sensorineural hearing loss and tinnitus.