Civamide, a synthetically produced, proprietary new chemical entity, is Winston’s flagship compound and is the active ingredient in several of the Company’s product candidates. Civamide produces analgesia by decreasing the activity of sensory neurons. Civamide, a TRPV-1 (transient receptor potential vanilloid-1) appears to preferentially affect type-C neurons by specific binding to a membrane receptor, the TRPV-1 receptor, which is coupled to a cation channel. Unlike local anesthetics which act to block the activity of all sensory neurons, the specificity of Civamide for type-C neurons seems to limit its sensory effects to the inhibition of pain transmission, thereby not impairing all sensations including touch, pressure, heat, and vibration, in addition to pain signals.
An oral dosage form of Civamide is in development for several indications, the first of which to be developed is for treatment of chronic neuropathic pain. The Company has filed an investigational new drug application (IND). Studies of animal pain models, done at the University of California, San Diego, have demonstrated that a single oral dose of Civamide can provide at least a week or more of effective analgesia.
If oral Civamide can achieve comparable results in human testing, this product would represent a potentially revolutionary advance beyond existing pain medications, whose analgesic efficacy usually lasts only a few hours.
Civamide Cream contains Winston’s proprietary TRPV-1 receptor modulator. Two Phase II studies of Civamide Cream involving 178 and 151 patients and one Phase III study of 695 subjects, have been completed, demonstrating substantial relief of the signs and symptoms of osteoarthritis pain with daily use. These trials enrolled both patients who were on a stable dose of oral NSAIDs or COX-2 inhibitors (Phase III ), or not on oral medications (Phase II). These studies indicate that Civamide is effective as a monotherapy as well as an adjunctive treatment.
Civamide Nasal Solution is a metered nasal spray containing Civamide that works through suppression of neuropeptides (e.g., SP and CGRP) of the trigeminal neural plexus thought to be involved in the pathogenesis of migraine and cluster headaches and PHN of the trigeminal nerve.
Phase II and Phase III studies in episodic cluster headache have demonstrated that Civamide Nasal Solution can substantially reduce cluster headache frequency following a single one-week course of treatment. A U.S. Phase III study and a European Phase III study have been completed.
Intra-articular Civamide is a formulation for intra-articular delivery of Civamide into a painful arthritic joint, either osteoarthritis or rheumatoid arthritis. Animal models of experimentally-induced arthritis have demonstrated potent anti-inflammatory and analgesic activity of intra-articular capsaicinoids that is mediated by SP, as well as SP’s promoting the proliferation of synoviocytes. It is expected that a single injection of intra-articular Civamide into an affected joint will provide prolonged analgesia and potentially could exhibit disease modifying effects. Intra-articular Civamide is currently in preclinical development. The Company possesses an exclusive worldwide license to utilize a patented, injectable delivery system, Biosphere®, as the vehicle for intra-articular Civamide.