PHARMACOTHERAPRY FOR XEROSTOMIA IN SJOGREN'S SYNDROME

DESCRIPTION (provided by applicant): Sjogren's syndrome (SS) is a slowly progressive inflammatory disease characterized by lymphocyte- mediated destruction of exocrine glands and internal organ involvement due to autoantibody production or pre- existing connective tissue disorder. Over time, progressive infiltration of lacrimal and salivary glands by mononuclear cells leads to diminished secretions, with resultant xerostomia (dry mouth) and xeropthalmia (dry eye) being the most prevalent symptoms. In Sjogren's patients, xerostomia leads to significant discomfort; interferes with activities such as speaking, chewing, and sleeping; and can result in numerous secondary clinical manifestations. Use of currently available treatments for xerostomia, including saliva substitutes and centrally acting parasympathomimetic secretagogues such as pilocarpine and cevimeline, provide transient relief, but patients often find these remedies costly, ineffective, inconvenient, and associated with uncomfortable side effects. Parion Sciences is developing 552-02, a novel epithelial sodium channel (ENaC) blocker, as a therapeutic for the indication of dry mouth. A 28-day, randomized, double-blind, placebo-controlled crossover, safety study (205S) was conducted to evaluate the safety and efficacy of 552-02 formulated as an oral rise. In study 205S, the oromucosal formulation of 552-02 was safe and well tolerated when administered 6 times daily for 28 days to patients with dry mouth associated with Sjogren's syndrome. Despite the small sample size in this exploratory study (n=30), patients' assessments of changes from baseline in symptoms of dry mouth using visual analog scales indicated 552-02 efficacy for mouth dryness, tongue dryness, and the ability to sleep, and for overall symptoms of dry mouth (global assessment). Based on these results, Parion is continuing to develop its xerostomia program and is planning a follow-up Phase II study that will be optimized to increase efficacy and patient convenience. Specifically, the proposed study (207S) is powered for efficacy measures and includes an increase in concentration of 552-02 and new trial design. Study 207S is a necessary step in the overall development program for 552-02 as a novel therapy for treating the symptoms of dry mouth associated with Sjvogren's syndrome. PUBLIC HEALTH RELEVANCE: Sjogren's syndrome is a disease that is, in part, characterized by severe dry mouth and dry eye. In Sjogren's patients, severe dry mouth leads to significant discomfort; interferes with activities such as speaking, chewing, and sleeping; and can result in other numerous disease conditions. Parion Sciences is developing a new drug that will be given as a mouth spray for the treatment of dry mouth associated with Sjogren's syndrome.