Pipeline
Gevokizumab (XOMA 052)
Gevokizumab (XOMA 052) is a potent monoclonal antibody with the potential to treat patients with a wide variety of inflammatory diseases and other diseases.
Gevokizumab binds strongly to interleukin-1β (IL-1β), a pro-inflammatory cytokine that has been shown to be involved in non-infectious uveitis including Behcet’s uveitis, cardiovascular disease, and other auto-inflammatory diseases. By binding to IL-1β, gevokizumab inhibits the activation of the IL-1 receptor, thereby modulating the cellular signaling events that produce inflammation.
XOMA has completed a successful proof-of-concept Phase 2 trial of gevokizumab in patients with Behçet's uveitis. As previously reported, all seven patients displayed rapid reduction of intraocular inflammation and improvement in visual acuity or other ophthalmic measures after a single treatment with gevokizumab and following discontinuation of immunosuppressive drugs such as cyclosporine and/or azathioprine. Follow-up results demonstrated that each of the patients re-treated with gevokizumab due to a recurring uveitis exacerbation responded again to gevokizumab treatment; some have received monthly treatments for one year or longer. Gevokizumab has been well-tolerated, and no drug-related adverse events have been reported.
Gevokizumab has been studied nearly 500 patients, with approximately 300 patients on treatment for six months. These studies have shown gevokizumab to be well-tolerated. XOMA holds rights to gevokizumab in the U.S. and Japan for non-cardiovascular indications, including uveitis, Behçet’s uveitis and acne, among others. Gevokizumab has Orphan Drug status for the treatment of Behçet’s disease in the U.S. and Europe.
Gevokizumab in Ophthalmology
Gevokizumab has potential for the treatment of non-anterior, non-infectious forms of uveitis, 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 non-infectious uveitis has been shown to be IL-1 mediated.
Behçet's (pronounced beh-CHETS) 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.
Based on these results, XOMA and Servier have elected to initiate a gevokizumab Phase 3 program to encompass multiple diseases categorized clinically as forms of non-infectious, non-anterior uveitis (NIU). 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 Proof-of-Concept Program
XOMA is conducting a proof-of-concept Phase 2 program designed to evaluate gevokizumab’s therapeutic potential in additional inflammatory diseases with IL-1β involvement. The studies will be focused on indications with well-defined endpoints and designed to show clear signals of efficacy in a relatively short period of time. By conducting this program in diseases with distinct pathophysiologies yet which have IL-1β-mediated inflammation in common, Servier and XOMA will be able to assess the clinical potential of gevokizumab in each and determine which indications merit further clinical development. The first of these trials, in moderate to severe acne vulgaris, is underway.
