First in class uveitis therapy -- Ph3 results highlighted at IOIS
Lux Biosciences’ Luveniq™ (LX211) Highlighted at International Conference on Ocular Inflammation
-- Results of LUMINATE Phase 3 Studies Presented by Principal Investigators from North America, Europe, and India--
JERSEY CITY, NJ (May 26, 2009): Lux Biosciences today announced that Luveniq (LX211, oral voclosporin) and its potential as a first-in-class treatment to reduce both active inflammation and disease recurrence in uveitis is being highlighted this week in a series of presentations at the 10th Congress of the International Ocular Inflammation Society (IOIS) in Prague, Czech Republic. Aspects of the Phase 3 LUMINATE clinical trial program for LX211 will be presented by principal investigators for the three-trial program, conducted in North America, Europe and India. Uveitis, the 4th leading cause of blindness, is a group of autoimmune diseases characterized by chronic inflammation of the eye. If approved by the relevant regulatory authorities LX211 has the potential to become the first oral therapy specifically approved for uveitis in most markets.
“Uveitis is a relatively common inflammatory eye condition with an incidence of 52.4 per 100,000 and a prevalence rate of 115.3 per 100,000 population,” explains Dr. David Gritz from the University of Missouri-Kansas City Eye Foundation at the IOIS-Symposium. “Uveitis is commonly misdiagnosed, and roughly 50% of patients with this ocular inflammation have another underlying autoimmune disease such as rheumatoid arthritis.
Attending physicians often prescribe high doses of corticosteroids, which have a myriad of serious systemic side effects. “Even though the SUN (Standardization of Uveitis Nomenclature) working group considers the primary outcome for successful corticosteroid sparing to be a reduction of systemic steroids to levels of 10 mg/day or less, in order to prevent severe side-effects associated with long-term systemic steroids use, physicians are not treating patients based on this recommendation,” states Dr. Bahram Bodaghi, Pitié Salpétrière Hospital Paris, France, in his presentation. According to a U.S.-based chart review of more than 500 patients, the current uveitis treatment pattern includes high doses (37 mg/day and above) of steroids on a long-term basis with limited use of steroid-sparing agents.
Dr. Virender Sangwan, Prasad Eye Institute, Hyderabad, India, comments in his presentation, “Uveitis is a disease that, until now, has not been studied in well controlled and adequately sized clinical programs. Therefore the disease is not well understood, there are no clear treatment patterns or guidelines.”
According to Dr. C. Stephen Foster from the Massachusetts Eye Research Institute in Cambridge, Massachusetts, LUMINATE is the first late stage clinical program to evaluate a corticosteroid-sparing agent in uveitis. Consisting of 3 well-controlled trials enrolling a total of 558 patients, LUMINATE is by far the largest clinical program in sight-threatening non-infectious uveitis. Three randomized double-masked, placebo-controlled, dose-ranging phase 2/3 trials examined the efficacy and safety of LX211 and placebo, all given orally twice a day. Of the three LX211 doses studied, 0.4 mg/kg BID had the most acceptable safety profile relative to the effect on the disease.
“The LX211-01 study included 218 patients with active non-infectious uveitis with a posterior (back of the eye) manifestation of the disease,” explains Dr. Talin Barisani-Asenbauer from the Medical University of Vienna, Austria. “In the LX211-01 study, the 0.4 mg/kg BID dose fully met the primary endpoint of superiority to placebo at both week 16 (p=0.008) and week 24 (p=0.027) for mean change from baseline in vitreous haze, which served as a validated measure for the inflammation of the posterior segment of the eye. The magnitude of the effect was >1 step change from baseline, demonstrating a clinically relevant benefit.”
As Dr. Quan Dong Nguyen, Wilmer Eye Institute at John Hopkins, Baltimore emphasizes in his presentation, “The 0.4 mg/kg BID dose, given in the LX211-02 study (232 patients with clinically quiescent disease) showed a reduction in exacerbation rate by 50% vs. placebo. The rate of inflammation recurrence at 6 months was measured using a pre-specified analysis that accounted for data censoring due to non-efficacy-related discontinuations. This reduction was statistically significant (p=0.044), thus confirming the positive results from LX211-01.”
Dr. Vishali Gupta, Post Graduate Institute of Medical Education and Research, Chandigarh, India, presents the results of the LX211-03 study. This study included 108 patients with active uveitis with an anterior (front of the eye) manifestation of the disease. In treated patients the cellular response in the front of the eye was reduced from an average of more than 25 anterior chamber cells per high power microscopic field to an average of 6 to 10 cells per high power field. However, since placebo-treated patients also improved in this study it was not possible to show that LX211 was effective for the rare subset of uveitis patients with refractory disease in the anterior portion of the eye. However, it is also noted that the placebo patients had by chance a lower burden of disease. The sub-set of patients receiving only topical corticosteroids which were tapered between weeks 4 and 16 did, in fact, flare, while the 0.4 mg/kg LX211 dose group did to a much lesser extent. The result is nearly statistically significant at weeks 16 and 24.
Dr. Marc D. de Smet of the University of Amsterdam and, Chairman of the Independent Data Monitoring Committee (DMC) will present a summary of safety in the LUMINATE Uveitis Program at the meeting. Of the three doses studied, the 0.4 mg/kg BID dose had the most acceptable safety profile relative to effect on the disease. The adverse effects on the kidney (8.2% of subjects with decrease from baseline by ??% in glomerular filtration rate vs. 4.1 % in placebo) and blood pressure (mean increase in systolic BP by 6 mm Hg) were overall moderate and manageable. Triglycerides and cholesterol were not elevated and had no negative impact on the cardiovascular safety profile. Hair growth (hirsutism) was observed in 5% of patients. Otherwise the safety profile was similar to placebo. Importantly, LX211 allows a reduction of corticosteroid dose to a near-physiologic range of 5 mg or less per day while maintaining the inflammation under control. Also, in reducing the rate of flares, LX211 spares patients from receiving rescue doses that averaged about 40mg of prednisone. Therefore, LX211 controls the disease while reducing the serious side effects associated with corticosteroids. Additional exploratory analyses were conducted in the context of the LUMINATE program, such as optical coherence tomography (OCT) to measure retinal thickness, and fluorescein angiography to measure vascular leakage, both sometimes associated with uveitis. Dr, Manfred Zierhut of the University of Tuebingen, Germany, reports on the use of diagnostic imaging using several case studies to highlight the effects.
Dr. James Rosenbaum of Oregon Health Sciences University, Portland, Oregon, summarizes the presentations of the LUMINATE data by addressing the question: How do we incorporate the LUMINATE data in the management of non-infectious uveitis? – A call for guidelines.
About Lux Biosciences
Lux Biosciences, Inc. is a privately held biotechnology company focused on ophthalmic diseases. The company has a staged product portfolio of potentially first-in-class therapies distinguished by their short-term path to commercialization and potential to generate high revenue growth. The portfolio includes:
• Two Phase 3 clinical-stage projects including: i) LUVENIQ™, the oral formulation of a next-generation calcineurin inhibitor (voclosporin) developed as steroid-sparing therapy for the treatment of sight-threatening non-infectious uveitis, and ii) LUMITECT™, a silicone matrix ocular (episcleral) implant that steadily releases therapeutic doses of cyclosporine A locally to the eye for the prevention of rejection in corneal transplant recipients. Both the LUMINATE pivotal clinical program for LUVENIQ for the treatment of uveitis, as well as the LUCIDA pivotal clinical program with LUMITECT™, for the prevention of corneal transplant rejection were initiated in early 2007 and include sites in North America, Europe and India. Enrollment in the LUMINATE program was completed in June 2008. Enrollment in the LUCIDA program was completed in March 2009. Lux Biosciences has licensed voclosporin from Isotechnika, Inc. for development in ophthalmic indications.
• LX214 is a novel topical eye drop formulation that entered human clinical testing for dry eye syndrome in February 2009. Based on Lux’s proprietary next-generation calcineurin inhibitor, LX214 is targeted towards other chronic inflammatory diseases of the eye, most notably dry eye syndrome, blepharitis and atopic keratoconjunctivitis.
• Several earlier stage projects based on proprietary product-enabling bio-erodible polymer technologies that facilitate targeted and sustained delivery of molecules to the eye.
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Posted: May 2009