LX211

Birdshot patients in the UK have participated in the LX211 trials. LX211 is a novel synthetic compound, an immunosuppressive molecule that acts like cyclosporine, is as effective, but  a lot less toxic with fewer side effects.  It can be used at a  lower dose.   There are studies going on in the UK, as well as across the US.   There is a lot of excitement about this product  which is the first uveitis medication to be tested in a randomized, controlled, masked clinical trial.  The drug trials have now finished and the drug is currently not licenced for use in the UK.

Author(s): Quan Dong Nguyen for the LUMINATE (Lux Uveitis Multicenter Investigation of a New Approach to Treatment) Uveitis Program Investigator Group

Address:  Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD

LX211 is a novel calcineurin inhibitor (CNi) possessing four-fold greater potency, an altered metabolic and PK/PD profile and potentially improved safety compared to the prototypical CNi, cyclosporine A.  Three pivotal dose-ranging clinical trials have been designed to evaluate the safety and efficacy of LX211 as a steroid-sparing agent for the treatment, control and maintenance of sight-threatening, non-infectious posterior, intermediate, panuveitis and anterior uveitis.  These global, prospective, double-masked, parallel-group, dose-ranging, placebo-controlled, randomized multicenter studies comprise the LUMINATE Uveitis Program, which is currently in progress.  In all studies, patients are randomized (2:2:2:1) either to one of three doses of LX211 (0.2 mg/kg, 0.4 mg/kg or 0.6 mg/kg b.i.d taken as capsules orally) or placebo.  Study LX211-01-UV (LUMINATE Active) will evaluate 210 patients with active predominantly posterior manifestations of their condition.  Study LX211-03-UV (LUMINATE Anterior) will evaluate 100 patients with active predominantly anterior manifestation of inflammatory disease.  A third study, LX211-02-UV (LUMINATE Maintenance) will evaluate LX211 in 220 patients whose disease is controlled and will be used to spare the use of systemic corticosteroid and, if applicable, to replace the patient’s current poorly-tolerated corticosteroid-sparing agent.  Primary endpoint: assessment of ocular inflammation according to the specifications of each study.  The primary endpoints in Protocol LX211-01-UV (LUMINATE Active) are mean change from baseline in graded vitreous haze after 16 weeks of therapy or at the time of rescue if earlier and mean change from baseline in graded vitreous haze after 24 weeks of therapy or at time of rescue, if earlier.  Protocol LX211-02-UV (LUMINATE Maintenance) will assess the proportion of subjects experiencing inflammatory exacerbation during 26 weeks of treatment. This is defined by a clinically significant deterioration in either eye for one or more of the following: graded vitreous haze, graded anterior chamber cells or visual acuity (Best Corrected Visual Acuity, BCVA).  Protocol LX211-03-UV (LUMINATE Anterior) will assess mean change in graded anterior chamber cells after 16 weeks of therapy or at the time of rescue, if earlier.  Secondary endpoints: Assessment of corticosteroid utilization, rates of exacerbation, quality of life, anterior segment inflammation, macular edema, and visual acuity and its relevance to support the indication sought.  Safety: Assessments will include the incidence and severity of adverse events, change from baseline in intraocular pressure and changes in laboratory values.  Conclusions: The LUMINATE uveitis program is the first clinical development program for regulatory approval of a corticosteroid-sparing immunosuppressive agent in different types of sight-threatening non-infectious uveitis.