XOMA Ltd. (Nasdaq:XOMA), a leader in the discovery and development of therapeutic antibodies, announced positive results from an open-label pilot study of XOMA 052 in patients with uveitis of Behcet's disease who were suffering from vision-threatening exacerbations despite maximal doses of immunosuppressive medicines. All seven patients who enrolled in the trial displayed rapid reduction of intraocular inflammation and improvement in visual acuity or other ophthalmic measures following a single treatment with XOMA 052, a therapeutic antibody candidate that inhibits the inflammatory cytokine interleukin-1 beta (IL-1 beta). The preliminary results of the first clinical trial of XOMA 052 in patients with uveitis of Behcet's disease were presented at the Annual Congress of the European League against Rheumatism (EULAR) in Rome, Italy.
Uveitis, or inflammation of the intraocular tissues of the eye, of Behcet's disease is one of the most severe forms of uveitis and affects approximately half of the patients with Behcet's disease. Unlike many forms of chronic uveitis, Behcet's uveitis is characterized by recurrent acute attacks or exacerbations. Without immediate treatment, major exacerbations of Behcet's uveitis may lead to retinal detachment, vitreous hemorrhage, glaucoma and eventual blindness. Symptoms include the accumulation of vitreous haze which can block eyesight or the loss of visual acuity and can manifest differently from patient to patient. For example, patients may go from 20/20 eyesight to loss of vision during the course of an exacerbation.
"Behcet's uveitis can lead to progressive and permanent loss of visual acuity. Unfortunately, there is no cure and current treatments are limited to corticosteroids and immunosuppressive drugs, all of which have significant side effects, especially when used on a chronic basis," explained Dr. Ahmet Gul, principal investigator of the pilot study and Professor of Medicine, Istanbul University, one of the largest centers of study for Behcet's disease in the world. "Over-expression of IL-1 beta and downstream pro-inflammatory cytokines play critical roles in Behcet's disease. Targeting IL-1 beta inhibits the inflammatory process and has the potential to improve eyesight in these patients without the toxic side effects of current therapies. We are encouraged with the data generated so far, notably that we saw very clear improvements in these patients following treatment with XOMA 052, despite the removal of immunosuppressive medicines."
Each of the seven patients presented with active exacerbations of uveitis despite receiving maximal doses of immunosuppressive medicines. Each received a 0.3 mg/kg intravenous infusion of XOMA 052 and simultaneously stopped taking immunosuppressive drugs such as cyclosporine and/or azathioprine. All continued treatment with low doses of corticosteroids. Patients' status was measured using multiple objective parameters associated with ocular health, including patients' visual acuity, vitreous haze score, anterior chamber cells, fundus score, and the patients' flare score.
All seven patients demonstrated improvement in intraocular inflammation starting within one day of treatment with a single dose of XOMA 052 and achieved clinically significant improvement of retinal problems and vitreous haze four to 21 days following treatment. Visual acuity improvements were evident following treatment with XOMA 052, and six out of seven patients remained in remission 28 days after a single treatment. Five patients received a second infusion between days 29 and 95 to blunt a developing exacerbation, and all responded to the second infusion. The drug appeared to be safe, and no drug-related adverse events were reported.
"The results of the XOMA 052 study show great promise for Behcet's patients suffering from recurrent uveitis, which can cause permanent vision loss," said Joyce Kullman, Executive Director of the Vasculitis Foundation. "Given that there is no satisfactory standard of care for treating Behcet's uveitis and at present the only therapeutic options are limited, developing an effective therapy is critical. XOMA 052 may offer leading-edge promising care for our patients."
"We have watched with great interest over the last several months as mounting preclinical and clinical evidence clearly demonstrate the potential of targeting IL-1 beta to treat inflammation in a broad range of diseases like diabetes, cardiovascular and gout," said Patrick J. Scannon, M.D., Ph.D., XOMA's Executive Vice President and Chief Medical Officer. "These data in Behcet's uveitis, in which all patients treated with XOMA 052 have shown marked improvement, highlight yet another potential application of XOMA 052 in treatment of inflammatory-mediated diseases. While we recognize that larger studies must be conducted, we are very pleased with these results."
"While we remain focused on developing XOMA 052 in patients with Type 2 diabetes and cardiovascular disease, the generation of these initial positive results in an orphan indication could provide an accelerated regulatory pathway," noted Steven B. Engle, Chairman and Chief Executive Officer of XOMA. "We believe the results of this study provide additional evidence of the importance of the role of IL-1 in inflammatory diseases and the potential value of XOMA 052."
Behcet's (pronounced beh-CHETS) disease is an orphan disease that causes chronic inflammation of the blood vessels, or vasculitis. Major symptoms can affect the neurological, pulmonary, gastrointestinal and cardiovascular systems, and hallmarks of the disease include painful ulcers in the mouth and on the genitals. Behcet's disease most commonly affects men and women in their twenties, thirties and forties, and it is typically more severe in men. An estimated 5,000 to 15,000 patients in the United States have Behcet's, and the disease is more common in Turkey, eastern Mediterranean countries, Japan and Korea.