Gevokizumab is a potent monoclonal antibody with unique allosteric modulating properties and the potential to treat patients with a wide variety of inflammatory and other diseases. Gevokizumab binds strongly to interleukin-1 beta (IL-1 beta), a pro-inflammatory cytokine, and modulates the cellular signaling events that produce inflammation. IL-1 beta has been shown to be involved in diverse array of disease states, including non-infectious uveitis (including Behçet's uveitis), cardiovascular disease, and other auto-inflammatory diseases.
Gevokizumab in Ophthalmology
Gevokizumab has potential for the treatment of non-anterior, non-infectious forms of uveitis (NIU), inflammation of the heavily vascularized layer of the eye. People with these types of uveitis may experience decreased vision, pain, light sensitivity and floaters. Uveitis can lead to permanent vision loss. The inflammation that leads to NIU has been shown to be IL-1 mediated.
Behçet's uveitis is one of the most severe forms of uveitis. It is characterized by recurrent acute attacks or exacerbations. Without immediate treatment, major exacerbations of Behçet’s uveitis may lead to retinal detachment, vitreous hemorrhage, glaucoma and eventual blindness. Treatment for Behçet’s uveitis is limited to corticosteroids and immunosuppressive medicines such as cyclosporine and azathioprine, all of which carry significant side effects that are detrimental to patients’ quality of life.
Gevokizumab demonstrated clinical activity in a pilot study of uveitis of Behçet’s uveitis as presented at the 2010 Annual Congress of the European League Against Rheumatism (EULAR), the 2010 International Congress on Behçet's Disease and the 2010 American College of Rheumatology Annual Scientific Meeting. Gevokizumab is designated by the U.S. FDA and the European Medicines Agency as an orphan drug to treat Behçet’s disease.
EYEGUARD™ Clinical Program
Based on these results, XOMA and Servier have initiated a global gevokizumab Phase 3 clinical program named EYEGUARD to encompass multiple diseases categorized clinically as forms of non-infectious, non-anterior uveitis (NIU). The EYEGUARD-A study is designed to determine gevokizumab's ability to treat active NIU. The Servier-run Phase 3 study in Behcet's uveitis patients, EYEGUARD-B, is designed to determine gevokizumab's ability to help patients with Behcet's uveitis experiencing an exacerbation while reducing steroid dosage. The EYEGUARD-C study will evaluate if gevokizumab allows physicians to reduce the corticosteroid dose used to maintain patients' NIU in a controlled state. This expanded program increases the potential U.S. patient population from the estimated 7,500 Behçet’s uveitis patients to an estimated 150,000 patients with NIU.
Gevokizumab Pyoderma Gangrenosum Program
In addition to the NIU clinical trials, we also are conducting a trial of gevokizumab in pyoderma gangrenosum (“PG”), a rare ulcerative skin disease. Based upon what we believe are compelling data from our pilot study in patients with PG, we met with the U.S. Food and Drug Administration (“FDA”) to solicit feedback on our proposed Phase 3 clinical development program. We've submitted the final prototcol to the FDA for final comment. The Phase 3 program is expected to include two double-blind, placebo-controlled clinical studies, each of which is designed to enroll approximately 60 patients with active PG. The primary endpoint is complete wound closure of the target ulcer at approximately four months. XOMA anticipates conducting these parallel studies in the United States and several other countries.
SERVIER Proof-of-Concept Program
Separately, SERVIER initiated a Phase 2 study to determine gevokizumab's ability to reduce arterial wall inflammation in patients with marked atherosclerotic plaque inflammation and who have experienced an acute coronary syndrome in the previous twelve months, as well as POC studies in polymyositis/dermatomyositis, giant cell arteritis, and Schnitzler syndrome.