Precision Betamethasone Microspheres for Transtympanic Delivery & SSNHL Treatment

DESCRIPTION provided by applicant New treatment options are needed for inner ear disorders including Meniereandapos s disease sensorineural hearing loss autoimmune inner ear disease and tinnitus In the absence of FDA approved drugs physicians use improvised treatments including the administration of off label steroids which lack safety and efficacy data These ad hoc approaches often fail to achieve the desired outcomes a result potentially attributable to insufficient and variable drug exposure in the inner ear Orbis Biosciencesandapos s extended release inner ear drug delivery platform Unison has the potential to significantly improve treatment for a wide range of otic disorders by maintaining precise and therapeutic drug levels in the inner ear for more than thirty days after a single cost effective intratympanic injection The Unison platform is a composite of drug loaded microspheres produced using Orbisandapos patented Precision Particle Fabrication technology that allow for precise control of drug release and a novel Fast Film forming Agent FFA that severs as both a diluent for microsphere injection and a film that holds the microspheres to the Round Window Membrane RWM allowing the microspheres to continuously deliver their drug payload to the inner ear for over a month The first product to use the Unison platform is ORB an extended release betamethasone for the treatment of steroid responsive otic disorders Upon successful FDA approval ORB will replace the current clinical practice of multiple intratympanic injections of aqueous suspensions spaced over the course of several weeks a treatment that is painful inconvenient and often ineffective Under SBIR Phase I Orbis successfully developed a prototype of Unison and ORB Orbis used its patented Precision Particle Fabrication technology to successfully encapsulate and control the in vitro release of betamethasone a potent glucocorticoid steroid Concurrently Orbis developed a FFA capable of affixing microspheres in the RWM for over thirty days and demonstrated that this novel FFA was non toxic in mice The objective of this SBIR Phase II proposal is to demonstrate the safety and efficacy of ORB in preclinical models for both small and large animals and to hold a pre IND meeting with the FDA in preparation for an IND filing during Phase III of this SBIR program Orbis will first establish the in vitro in vivo correlation of ORB in guinea pigs along with shelf stability testing of the ORB components Aim Subsequently Orbis will characterize the safety pharmacology and toxicology of ORB in guinea pigs using an acute ototoxicity model Aim Finally Orbis will establish the dose response curve of ORB in a large animal sheep model Aim to characterize the dose requirements in an animal with inner ear fluid volume near the size of the human At the completion of this Phase II SBIR program Orbis will have established the safety and efficacy of ORB to achieve steady concentration of steroid in the inner ear for a minimum of thirty days in both small and large animal models thereby positioning the resultant formulation for IND enabling preclinical trials PUBLIC HEALTH RELEVANCE There are no FDA approved drugs for the treatment of inner ear diseases that afflict millions of Americans ever year In their place physicians often prescribe drugs off label that whether delivered orally or through local injection to the ear lack safety data and show widely variable clinical responses Orbis Biosciencesandapos s innovative inner ear drug delivery platform will enable cost effective local delivery and extended release of new and existing drugs thereby providing physicians and patients new safe and effective treatments for debilitating diseases of the inner ear