Surfactant Platform (OP02xx)
The first product in the surfactant platform program, OP0201, is being developed as a potential first-in-class treatment option for otitis media (OM). OM is often caused by Eustachian tube dysfunction (ETD). OP0201 is a nasal aerosol, drug-device combination product comprised of a novel formulation of a surfactant (dipalmitoylphosphatidylcholine [DPPC]) and a spreading agent (cholesteryl palmitate [CP]) suspended in a propellant. The product is administered intranasally via a pressurized metered-dose inhaler (pMDI). OP0201is intended to be used to restore the normal physiologic activity of the Eustachian tube (ET), which is a small tube that connects from the chamber of the middle ear to the back of the nasopharynx. Together, the active ingredients in OP0201 effectively absorb to the air-liquid interface of the mucosa and reduce the interfacial surface tension of the ET, which reduces passive pressure required for the ET to open. In other words, OP0201 promotes ‘de-sticking’ of the ET so that ventilation of the middle ear is restored.
About Otitis Media
Otitis media (OM) is a generic term without reference to a specific etiology or pathogenesis and best regarded as a spectrum of diseases of the middle ear. OM is a very common condition and a leading cause of healthcare visits and antibiotic prescriptions. Common forms of OM are acute otitis media (AOM) and otitis media with effusion (OME). Both AOM and OME can occur episodically or persist for long periods of time. If reoccurrence is frequent (i.e., three episodes within six months), the patient is diagnosed with recurrent acute otitis media (RAOM). If middle ear effusion (MEE) persists in the middle ear for longer than three months, then the patient is diagnosed with chronic otitis media with effusion (COME).
AOM is very common and can affect both children and adults. AOM is usually a short-term inflammation of the middle ear, characterized by the sudden onset of one or more signs or symptoms of acute middle ear inflammation (e.g., ear pain, fever or irritability) in the presence of MEE. AOM is often preceded by upper respiratory symptoms including cough and rhinorrhea. Micro-organisms (viral or bacterial) in the nasopharynx may reflux into the middle ear, where they adhere and colonize resulting in an ear infection. AOM is extremely common in young children, many of whom will have multiple AOM episodes (RAOM) over the course of months or even years.
OME is also very common and can affect both children and adults. OME is characterized by a non-purulent (non-infected) MEE without sudden onset of signs or symptoms of an acute ear infection. Symptoms usually involve conductive hearing loss or aural fullness caused by impaired transduction of sound waves through the fluid-filled middle ear, but typically without pain or fever. OME often follows an AOM episode and can last for several months or up to a year, which can result in speech and learning delays in children and other morbidities in both children and adults. There are several predisposing factors that have been associated with OME including environmental (e.g., bottle feeding, day-care setting, allergies to common environmental entities, cigarette smoke), age (higher incidence in pre-school age children), and ETD. Like AOM, patients can experience multiple OME episodes over the course of months or years (recurrent OME; ROME). If MEE persists for longer than three months, then the patient is diagnosed with COME and is often considered as a surgical candidate to insert tympanostomy tubes to facilitate ventilating the middle ear.
The Eustachian Tube
An important component of middle ear health is a normally functioning Eustachian tube (ET). The ET is a small cilia-lined passageway that connects the middle ear to the back of the nasal cavity (nasopharynx). Its primary functions are to protect, drain, and ventilate the middle ear. Normally, it is collapsed, preventing material from entering the middle ear. The ET opens periodically upon swallowing, chewing, yawning, or when a pressure differential exists between the middle ear and the external environment. When the ET becomes blocked or does not open normally, ETD occurs.
Current Treatments Options
To date, no drug product has been approved to treat OM. Antibiotics are commonly used to treat AOM patients who present with signs and symptoms of infection, but antibiotics have no effect on viral infections or OME which is a non-infectious condition. More importantly, antibiotics do not prevent recurrent AOM, recurrent OME or chronic OME. Topical steroids, antihistamines, and decongestants have not been shown to be effective as OM treatments or to prevent OM. In addition, the American Academy of Otolaryngology—Head and Neck Surgery recommends against the use of these drugs in patients with OM. The only option today to treat and possibly prevent RAOM, ROME or COME, is to perform a surgery where the tympanic membrane is perforated to improve drainage and ventilation of the middle ear (myringotomy or tympanostomy tube insertions). However, surgery is not always an effective solution for all patients as many continue to suffer with OM or its complications, and sometimes require repeat surgeries. Managing recurrent and chronic OM drives billions of dollars in healthcare costs and results in millions of surgical procedures in children and adults around the world. There is a clear unmet need for a safe, non-antibiotic, non-surgical option for patients.
In 2016, the U.S. Food and Drug Administration (FDA) permitted marketing of a medical device that uses a small intranasal balloon inserted into the ET to treat persistent ETD in adults. However, like OM, no drug product has been approved for the prevention of ETD.
Impact on Patients
The pathophysiology of OM and ETD are closely related. Both conditions can arise as a result of upper respiratory tract infections, allergies, and other inflammatory mediators and one condition can perpetuate the other condition. There are more than 700 million cases of OM and ETD around the world every year, half of which occur in children under 5 years of age. In the U.S. alone, there were more than 15 million visits to physicians during 2014 related to OM and ETD. It is one of the most common diseases seen in Pediatric and Otolaryngology practices and is the most frequent reason children consume antibiotics or undergo surgery.