By Fred Gebhart
SAN FRANCISCO -- October 28, 2009 -- Voclosporin shows promise as an oral agent that can modify the course of noninfectious uveitis, researchers stated here at the 2009 Joint Meeting of the American Academy of Ophthalmology and Pan-American Association of Ophthalmology (AAO-PAAO).
In phase 2/3 clinical trials conducted in the United States, Europe, and India, voclosporin controlled inflammation associated with uveitis and significantly delayed recurrence of inflammatory exacerbations. Patients also reduced corticosteroid use to 5 mg/day or less.
"This product is suitable for chronic use," said Bahram Bodaghi, MD, Pitié Salpétrière Hospital, Paris, France, on October 26. "Voclosporin reduced recurrence of inflammation by 50% and may increase the interval between inflammatory relapses 20 to 24 months compared with 10 months with placebo in this trial."
"Inflammation is a direct trigger of vision loss," he added. "This result suggests that this agent can alter the course of the disease and lead to improved clinical outcomes."
The double-blind, placebo-controlled trials compared 3 different doses of voclosporin with placebo. The LX211-01 study followed patients with active, sight-threatening uveitis in the posterior segment, and LX211-02 studied clinically inactive uveitis in any location within the eye.
Patients in LX211-02 had a mix of intermediate, intermediate and anterior, posterior, and panuveitis. Patients discontinued existing immunomodulating therapy at the start of the trial and steroids were tapered to 5 mg/day or less on a standard 12-week schedule. Patients in the 3 active-ingredient arms used oral voclosporin 0.2, 0.4, or 0.6 mg/kg. The original 26-week trial was extended to 52 weeks.
At week 26, the 0.4-mg/kg dose reduced inflammatory exacerbation rates by 50% compared with placebo, Dr. Bodaghi reported. The other 2 doses were less effective in reducing exacerbations. Patients in the 0.4-mg/kg arm also showed a significant reduction in steroid use. The 0.4-mg/kg arm also showed preservation of visual acuity from baseline levels while the other active-ingredient arms and the placebo arm had decreased visual acuity.
Results of the LX211-01 study in patients with active sight-threatening posterior uveitis were similar, reported Quan Dong Nguyen, MD, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland. Patients in the 0.4-mg/kg arm showed significant reduction of vitreous haze without the sustained use of high doses of corticosteroids.
"The effect was rapid, robust, and sustained," said Dr. Nguyen. "Control of inflammation is critical to the preservation of visual acuity."
Pooled safety data shows a promising adverse event profile, he continued. Patients on the 0.4-mg/kg dose showed increased blood pressure (6.1 mm Hg systolic, 4.2 mm Hg diastolic), but the changes were easily managed.
Researchers also noted a reversible dose-related impairment in renal function. There were no serious ocular adverse events in any of the treatment arms. Dr. Nguyen recommended monitoring of blood pressure and serum creatinine for patients on voclosporin.
[Presentation title: Luveniq (LX211/Voclosporin) as Corticosteroid-Sparing Therapy in Clinically Quiescent Sight-Threatening Noninfectious Uveitis: Results of the LX211-02 Study of the LUMINATE Clinical Program. Abstract PA026.
AND
Voclosporin (LX211) as Corticosteroid-Sparing Therapy for Posterior Active Sight-Threatening Noninfectious Uveitis: Results of the LX211-01 Study of the LUMINATE Program. Abstract PA027]
E-Mail this DGDispatch to a colleague
