Ophthalmology Therapeutic Roundup — April 27, 2017

Shire Initiates Phase 3 Clinical Trial Program for SHP640 in Infectious Conjunctivitis for Adults and Children

SHP640 is under investigation for both adenoviral and bacterial conjunctivitis
Clinical trial program plans to enroll more than 2,700 patients in U.S. and international sites

Shire announced the initiation of the Phase 3 clinical development program for SHP640, a combination broad spectrum antiseptic and corticosteroid in development for the treatment of  infectious conjunctivitis in adults and children. SHP640 is being evaluated for both adenoviral and bacterial conjunctivitis, which are both highly contagious diseases of the ocular surface.[i]  

“The initiation of our Phase 3 clinical trial program for SHP640 in infectious conjunctivitis marks an important milestone for Shire and our commitment and ability to advance clinical candidates that address areas of significant unmet need in ophthalmics,” said Philip J. Vickers, Ph.D., Head of Research and Development, Shire. “SHP640 is a strong strategic fit with our ophthalmics portfolio and interest in pursuing treatment options where innovation is needed.” 

SYNCHRONIZE, the Phase 3 clinical program for SHP640, will include four multi-center, randomized, double-masked, placebo-controlled studies – two for adenoviral conjunctivitis and two for bacterial conjunctivitis. These multi-center studies plan to enroll more than 2,700 patients to investigate the efficacy of SHP640 in adenoviral and bacterial conjunctivitis, and its safety and tolerability. The first patient has been enrolled in the U.S., with international clinical trial sites expected to open in Q3 2017.  

“Infectious conjunctivitis presents a clinical challenge because differentiating between bacterial and adenoviral causes can be problematic due to the considerable overlap in their respective clinical presentations and because current treatment options are limited to bacterial causes only,” said David G. Hwang, MD, FACS, Professor and Vice Chair of Ophthalmology and Director of the Cornea Service and the Refractive Surgery Service, University of California, San Francisco. “A single treatment option that could treat both adenoviral and bacterial conjunctivitis, and aims to address unnecessary antibiotic use, would fulfill an unmet need. SHP640 is a promising candidate in this regard. I commend Shire for pioneering a comprehensive research program for this ocular surface condition.”[ii]  

Conjunctivitis, often referred to as “pink eye,” is an inflammation of the outer mucous membrane overlying the eye and the under-surface of the eyelids, known as the conjunctiva. It is a highly contagious ocular disease characterized by redness, discharge, pain and photophobia.1^,[iii] Annually, there are approximately 6 million cases of acute conjunctivitis in the United States, the majority of which are infectious,¹ and approximately 5.2 million cases of infectious conjunctivitis in the EU.[iv] There are currently no approved prescription treatment options indicated for both types of infectious conjunctivitis.

About SHP640
SHP640 is a broad spectrum antiseptic (povidone-iodine [PVP-I], 0.6%), and anti-inflammatory steroid (dexamethasone, 0.1%) combination under investigation for the treatment of adenoviral and bacterial conjunctivitis in adults and children. The treatment regimen being studied for SHP640 is one drop, four times per day, for seven days.

Shire acquired SHP640 (formerly known as FST-100) through the acquisition of Foresight Biotherapeutics Inc., in August, 2015.

The Phase 2 proof-of-concept efficacy and safety clinical trial program for SHP640 involved two studies in adenoviral conjunctivitis – one three-arm study and another two-arm study. While the two-arm study showed a trend toward efficacy, there were too few subjects testing positive for a viral presence for the study to deliver meaningful results, and it was not statistically significant. In the three-arm study, patients were randomized to receive SHP640, PVP-I or vehicle four times daily for five days. Patients treated with SHP640 showed a statistically significant improvement in rates of clinical cure and viral eradication vs. vehicle at Day 6 (30.6% vs. 6.4%, p=0.0033). In the same trial, there was a trend toward clinical significance for SHP640 versus PVP-I (30.6% vs.18.0%, p=0.1432). The most common treatment emergent adverse events in the three-arm Phase 2 study were corneal infiltrates (19%), punctate keratitis (22.4%) and eyelid edema (12.1%).[v] Pre-clinical experiments were conducted to evaluate bacterial killing speed of SHP640 against pathogens that may cause bacterial conjunctivitis, and the resulting data support further exploration.

About Infectious Conjunctivitis
Commonly characterized by redness, discharge, pain and photophobia, infectious conjunctivitis more specifically refers to inflammation of the ocular surface most commonly caused by either a virus or bacteria.^1,3Both forms of infectious conjunctivitis are highly contagious and easily transmitted,1 causing lost work and school days, as well as increased healthcare costs and risks from unnecessary antibiotic prescriptions.[vi] If untreated, the condition may remain highly contagious for up to two weeks after signs and symptoms begin.6While both adults and children are susceptible to infectious conjunctivitis, children are more likely to develop the bacterial infection, while adults more often suffer from adenoviral conjunctivitis.3^,6 Annually, there are approximately 6 million cases of acute conjunctivitis in the United States, the majority of which are infectious,¹and approximately 5.2 million cases of infectious conjunctivitis in the EU.4   

Shire’s Commitment to Ophthalmics
In May 2014, Shire entered into ophthalmics, solidifying its commitment to growing in this emerging therapeutic area. Shire’s multi-faceted approach to discovery, development and delivery of innovative treatments for both rare diseases and specialty conditions includes our efforts to address areas of unmet need in eye care.

The expansion of Shire’s ophthalmics business has been driven by a combination of strategic acquisitions and organic growth. Committed to establishing its profile as an emerging global leader in ophthalmics, Shire is focused on building its portfolio to include treatment options for rare diseases and those for anterior and posterior segment eye conditions. In four years, Shire has made several acquisitions, including of Foresight Biotherapeutics, SARcode Bioscience, Premacure AB and BIKAM Pharmaceuticals, which have helped bolster Shire’s early-, mid- and late-stage ophthalmics pipeline. The Company currently has its first marketed product and a pipeline of investigational-stage candidates in infectious conjunctivitis and glaucoma.