LEXINGTON, Mass.—Sharing a vision of developing an innovative treatment for relieving dry eye disease, both Shire plc and Durham, N.C.-based Parion Sciences Inc. have entered into a lease agreement which grants Shire the exclusive worldwide rights to develop and commercialize P-321, an investigational epithelial sodium channel (ENaC) inhibitor, which allows tears to flow. Nearly 30 million people in the United States report symptoms consistent with dry eye syndrome, and with an aging baby boomer population rising, these numbers will only increase.
A Phase 2b study of P-321 is expected to begin after consultation with health authorities, Shire stated in a May 1 press release.
The prevalence of dry eye syndrome broadly ranges from 6 to 34 percent in adults globally. Dry eye syndrome is a multifactorial disease of the ocular surface that is often chronic and may be progressive. The disease is most commonly associated with eye dryness and overall eye discomfort, as well as stinging, burning, a gritty feeling or fluctuating blurry vision. If left untreated, this condition can lead to pain, ulcers or scars on the cornea and some loss of vision.
Aging and gender are recognized as traditional risk factors of chronic dry eye syndrome while modern risk factors include prolonged digital/computer screen time, contact lens wear and cataract or refractive surgery.
Shire’s proposed treatment, P-321, is being developed to address tear volume deficiency and promote ocular surface healing. While further clinical trials are needed to fully evaluate its safety profile and efficacy, P-321 is a novel molecule that is believed to address dry eye syndrome by inhibiting ENaC, which is believed to block the absorption of tears.
Cyclosporine, an anti-inflammatory medication, is the only prescription drug available to treat dry eye, according to the National Institutes of Health. It decreases corneal damage, increases basic tear production and reduces symptoms of dry eye, while P-321 helps keep the ocular surface hydrated.
“Ophthalmics is a continued focus for Shire, and the program for P-321 will benefit from our development and commercial infrastructure and expertise,” Dr. Flemming Ornskov, CEO of Shire, stated in a news release. “This is an opportunity to apply our knowledge and experience from ophthalmics and dry eye disease for further innovation in this space. If approved, P-321 would expand our eye-care portfolio.”
Paul Boucher, president and CEO of Parion, said, “Advancing P-321 with Shire, an emerging global leader in ophthalmics, offers the expertise and resources to move this promising potential therapy for dry eye sufferers forward.”
The specific terms of the deal were not disclosed, but it has been revealed that Shire will make an initial $20-million upfront license payment with an additional $20-million payment based on the achievement of a near-term development milestone. Parion is entitled to receive additional potential milestone payments adding up to a total potential deal value of up to $535 million.
Under the agreement, Parion has the option to co-fund additional stages of development in exchange for enhanced tiered double-digit royalties, along with the option to co-fund commercialization activities and participate in the financial outcome from those activities.
On Nov. 1, 2016, Parion announced that the first-in-human trial was encouraging, identifying an agent (P-321) that was associated with signs of improvement in tear function, and discovered the EnaC blocker to be a safe and well-tolerated therapy in patients with symptoms of mild-to-moderate dry eye disease compared with placebo.
José L. Boyer, vice president of research and ophthalmology at Parion Sciences, and a lead author of the P-321-101 study discussed the rationale behind the development of P-321.
“The inhibition of ENaC on the ocular surface is predicted to block pathways for tear absorption and at the same time provide a driving force for water secretion, resulting in increased hydration of the ocular surface,” Boyer states.
The P-321 ophthalmic solution was evaluated in a single-center, dose-escalation, randomized, double-masked, placebo-controlled Phase 1/2a trial to determine its safety and tolerability in patients with mild-to-moderate dry eye compared with placebo, says study co-author Dr. Gary Foulks, emeritus professor of ophthalmology with the University of Louisville.
No subjects left the study as a result of an adverse event. Specifically, nine ocular drug-related events developed in seven patients, all of which were considered to be mild. Two cases of mild conjunctival hyperemia developed, one in a patient assigned to P-321 and one in a patient assigned to placebo.
A Phase 1/2a placebo-controlled, dose-escalation clinical study in 53 patients has also been completed, which evaluated the safety and tolerability of P-321 in patients with mild to moderate dry eye disease. No adverse effects were noted.
