This article is part of PharmTech's supplement "Injectable Drug Delivery."
Otonomy has developed a formulation platform that enables local delivery of drugs into the ear to treat middle- and inner-ear
conditions such as Meniere's disease*, certain forms of hearing loss, and infection. The diseases have traditionally been
treated by surgical means. I understand the company had an unusual beginning. Can you tell me about that?
The genesis of the idea for Otonomy came when Jay Lichter, a venture capitalist and the company's CEO, experienced severe
vertigo while driving in January 2008. He made his way to the clinic of Jeffrey Harris, professor and chief of the Division
of Otolaryngology–Head & Neck Surgery at the University of California, San Diego, in February of that year. Harris diagnosed
Lichter with Meniere's Disease. Lichter, a serial entrepreneur, and Harris discussed the potential of forming a biotech company
to develop targeted therapeutics specifically for ear disorders—and in April 2008, Otonomy was born.
Otonomy's Chief Scientific Officer Carl LeBel
Could you describe the state-of-the-art for these kinds of therapeutics?
At this time, it remains a challenge to get therapeutics into the middle and inner ear. The only targeted delivery available
requires a surgeon to insert a tube into the middle ear and infuse drugs through it for the treatment of otitis media. Some
physicians today employ a technique in which they inject drugs via a syringe into the middle ear, referred to as intratympanic administration. These drugs are typically formulations approved
for intravenous administration, yet no one has studied their suitability for direct access to the middle or inner ear. Beyond
that, there's the additional problem of drainage. Fluid drains from the ear through the Eustachian tubes, and therefore drugs
can't remain in the compartment long enough to provide much therapeutic benefit.
Oral delivery of therapeutics had also been tried. But the doses required to ensure therapeutic benefit to the ear are sometimes
so high as to risk inducing some kind of systemic toxicity. The ideal would be to deliver a drug directly to the middle ear
in such a way as to reduce elimination through the Eustachian tubes, and limit systemic exposure.
Is that what Otonomy has developed?
Essentially yes. Lichter and Harris reasoned that they could overcome these challenges if they could produce a formulation
that kept drugs in the middle ear, and is also safe and tolerable. The goal was to focus on an injectable formulation for
intratympanic delivery and optimal retention of the drug, allowing it to diffuse through the round window membrane of the
cochlea and gain access to the inner-ear fluids.
Otonomy has developed a formulation that is essentially a mixture of copolymers (polyethylene glycol and polypropylene) combined
with a steroid. Key to this mixture's suitability is its thermo-reversible properties. At room temperature, [the mixture]
is a solution. After the mixture is injected into the middle ear, the temperature rises to body temperature, and the mixture
transitions to a gel state. We can also manipulate the relative concentrations of the gel's components to alter the temperature
at which the mixture transitions from solution to gel. We refer to our lead formulation as OTO–104, which is a steroid in
Poloxamer 407 and might be useful in sinusitis surgery and laryngeal surgery to prevent scarring.