XOMA Corporation, a leader in the discovery and development of therapeutic antibodies, announced the phase 3 EYEGUARD-B study of gevokizumab in patients with Behçet's disease uveitis, run by its partner Servier, an independent French pharmaceutical research company, did not meet the primary endpoint of time to first acute ocular exacerbation.
"Although the study did not achieve its main objective, we did see signals of drug activity such as preserved visual acuity, less severe ocular exacerbations and a reduced incidence of reported macular edema in patients treated with gevokizumab," said Paul Rubin MD, senior vice president, research and development and chief medical officer.
"We will continue to work closely with our partner, Servier, and uveitis experts to conduct a thorough analysis of the data to fully understand gevokizumab's impact on several clinically relevant endpoints."
"The initial observations seen in the secondary endpoints are clinically important and meaningful to both clinicians and Behçet's disease uveitis patients. We look forward to learning more," stated Dr. Ilknur Tugal-Tutkun, international coordinator for the EYEGUARD-B study and professor of ophthalmology, head, ocular immunology and uveitis service at Istanbul University, Istanbul Faculty of Medicine, Department of Ophthalmology.
"In recent years, our public focus has been on gevokizumab. However, during that time, we have significantly advanced other assets in our pipeline including XOMA 358, for which we completed a positive phase 1 study showing it is active in down-regulating the insulin receptor and shows potential in treating patients who experience endogenous over-production of insulin, and XOMA 089, our late preclinical anti-TGFß monoclonal antibody with potential in immuno-oncology and fibrosis," said John Varian, chief executive officer of XOMA.
"We will focus our efforts on creating value with these pipeline assets and reduce expenses where appropriate. While we continue to evaluate the data from EYEGUARD-B, the EYEGUARD-A and C studies, in the broader range of non-infectious uveitis, are still recruiting."
Gevokizumab appeared to be well tolerated in the trial. Adverse events were comparable between gevokizumab and placebo treated groups.
The objective of the phase 3 EYEGUARD-B study (A randomisEd, double-masked, placebo-controlled studY of the Efficacy of GevokizUmAb in the tReatment of patients with Behçet's Disease uveitis) was to demonstrate the superiority of gevokizumab, compared with placebo, on top of the current standard of care in reducing the risk of Behçet's disease uveitis exacerbations and to assess the safety of gevokizumab. The study was designed to enroll patients with a history of Behçet's disease uveitis with ocular involvement of the posterior segment who had experienced a recent ocular exacerbation that was treated successfully with high doses of corticosteroids.
The trial enrolled a total of 83 patients in the core part of the study (40 on gevokizumab and 43 on placebo). Patients were randomized to either a 60 mg dose of gevokizumab or placebo administered subcutaneously once monthly on top of their current immunosuppressive and corticosteroid therapies. They were randomized when they reached the step of 20 mg/day equivalent oral prednisone and continued a standardized tapering regimen until they reached 5 mg/day during double-masked treatment.
The primary endpoint was the time to first acute ocular exacerbation. Secondary endpoints included total number of exacerbations, best corrected visual acuity, vitreous haze, retinal lesions, fundus assessments and macular edema.
Behçet's disease is an orphan disease that causes chronic inflammation of the blood vessels (vasculitis). Major symptoms can affect the neurological, pulmonary, gastrointestinal and cardiovascular systems. Painful ulcers in the mouth and on the genitals are hallmarks of the disease. In the United States, an estimated 15,000 individuals have Behçet's disease.
Behçet's disease uveitis is one of the most severe forms of non-infectious uveitis and affects approximately 50 per cent of those with Behçet's disease. It is characterised by recurrent unpredictable acute attacks or exacerbations. Without immediate treatment, major exacerbations of Behçet's uveitis may lead to retinal detachment, vitreous hemorrhage, glaucoma and eventual blindness. Symptoms, which most often include acute retinal lesions and the accumulation of vitreous haze that can block eyesight or the loss of visual acuity, can manifest differently from patient to patient. Available treatments for Behçet's disease uveitis are limited to corticosteroids and off-label use of immunosuppressive drugs and biologics, all of which can have significant side effects when used on a chronic basis.
Gevokizumab is a potent monoclonal antibody with unique allosteric modulating properties. It has 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 a diverse array of disease states, including non-infectious and Behçet's disease uveitis, cardiometabolic diseases and other auto-inflammatory diseases.
Gevokizumab currently is being studied in multiple indications. Global phase 3 clinical programs are underway in Behçet's disease uveitis, non-infectious uveitis and pyoderma gangrenosum.