Partnerships
Lux Biosciences
On May 25, 2006, Isotechnika Inc. signed an agreement with Lux Biosciences, Inc. (Lux) of Jersey City, New Jersey granting Lux worldwide rights to develop and commercialize Isotechnika’s lead drug, voclosporin, referred to as LX211 by Lux, for the treatment and prophylaxis of all ophthalmic diseases.
Their most advanced development program in uveitis has a worldwide market size of 500,000 patients. Uveitis refers to immune mediated, chronic inflammation or swelling of the eye's structures.
Official notification from the European Medicines Agency granting orphan medicinal product designation for voclosporin for the treatment of chronic, non-infectious uveitis was received on September 14, 2007. This designation provides a variety of incentives, including market exclusivity for up to 10 years following approval, fee reductions and free scientific advice. Previously in January 2007, Lux was granted orphan drug status for voclosporin for non-infectious, intermediate and pan uveitis from the FDA in the United States.
Lux received "Fast-Track" designation from the FDA for voclosporin for the treatment of uveitis in August 2007. "Fast-track" designation will provide various means to expedite the development and review of voclosporin. The process could be facilitated through meetings and other correspondence with the FDA reviewers, consideration for priority review, and the ability to submit portions of a New Drug Application (NDA) early for review as part of a "rolling" submission.
Lux initiated pivotal trials of voclosporin in uveitis in February, 2007. The three randomized, double-masked, dose-ranging and placebo-controlled trials comprising the LUMINATE Program, the largest clinical program ever conducted in uveitis, enrolled 558 patients in 7 countries (United States, Canada, United Kingdom, France, Germany, Austria and India). The key results in the LUMINATE trials were:
- Overall, of the 3 doses studied, the 0.4 mg/kg BID dose had the most acceptable safety profile relative to effect on the disease. Isotechnika, Inc. previously reported that 0.4 mg/kg BID demonstrated both efficacy and an acceptable safety profile in their clinical trial of voclosporin in plaque psoriasis, which is in the range of the maintenance dose of voclosporin anticipated for use in kidney transplantation.
- Study LX211-01 enrolled 218 patients with active non-infectious uveitis with posterior manifestation of the disease. The 0.4 mg/kg BID dose fully met the primary endpoint of superiority to placebo at both weeks 16 (p=0.008) and week 24 (p=0.04) for mean change from baseline in vitreous haze, a validated measure of inflammation of the posterior segment of the eye. The magnitude of the effect was >1 step change, demonstrating a clinically relevant benefit.
- Study LX211-02 enrolled 232 patients with clinically quiescent disease. The 0.4 mg/kg BID dose showed a reduction by 50% vs. placebo in rate of recurrence of inflammation at 6 months. The study did not meet the primary analysis endpoint of all-cause therapeutic failure at 6 months as the drug effect on inflammation was diluted by discontinuations that were unrelated to inflammation. This was due to a pre-specified analysis that accounted for data censoring due to non-efficacy-related discontinuations. However, the reduction in inflammation vs. placebo by 50% was statistically significant (p=0.046), thus confirming the positive results from LX211-01.
- Study LX211-03 enrolled a narrow sub-set of 108 patients with active uveitis with anterior manifestation of the disease. The efficacy of the voclosporin dose groups and placebo did not separate during the steroid taper; all showed an improvement by >1 step mean reduction from baseline in anterior chamber cells, a validated measure of inflammation in the anterior segment of the eye. This study, which is not critical for approval was added to encompass a sub-set of patients affected by anterior chamber disease, turned out to be underpowered owing to greater than expected variability.
On February 17, 2009, Isotechnika announced that Lux commenced a First-in-Man (Phase 1) trial with LX214, a proprietary topical ophthalmic solution containing voclosporin as the active ingredient for dry eye syndrome. Dry eye syndrome is one of the most common conditions treated by eye physicians and is usually caused by a problem with the quality and quantity of the tear film that lubricates the eyes resulting from chronic inflammation of the tear-producing lacrimal gland.