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 disease 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 disease uveitis (BDU) is one of the most severe forms of uveitis. It is characterized by recurrent acute attacks or exacerbations. Without immediate treatment, major exacerbations of BDU 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 BDU 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 of two Phase 2 clinical studies in Behçet's disease uveitis (BDU), XOMA and Servier 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 BDU 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.
In September 2014, XOMA initiated a U.S. clinical trial of gevokizumab in patients with BDU, EYEGUARD-US, to supplement data from Servier's EYEGUARD-B study being performed outside the U.S. and the ex-U.S. data previously generated from two Phase 2 trials of BDU patients. Upon receipt of successful results from the EYEGUARD-B study, XOMA plans to request a pre-BLA meeting with FDA. EYEGUARD-US is designed to supplement the Agency’s need for information in U.S. patients, including potentially serving as a second pivotal study.
EYEGUARD-B reached the pre-determined target exacerbation event on May 28, 2015.
More information on the EYEGUARD studies can be found at eyeguard-study.com
Gevokizumab Pyoderma Gangrenosum Program
In addition to the NIU clinical trials, we also are conducting a Phase 3 clinical program of gevokizumab in patiemts with 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. The Phase 3 program was initiated in November 2014 and includes two double-blind, placebo-controlled clinical studies, each of which is designed to enroll 58 patients with active PG. The primary endpoint is complete wound closure of the target ulcer at approximately four months.
Additional SERVIER Studies
Separately, SERVIER initiated a Phase 2 study in patients with diabetic nephropathy as well as POC studies in polymyositis/dermatomyositis, giant cell arteritis, and Schnitzler syndrome.