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UVEITIS

The Disease: Uveitis is an autoimmune disease resulting in chronic inflammation of the eye. There is substantial evidence indicating the involvement of T-lymphocytes, key immune system cells involved in inflammatory processes, in the development of uveitis.

Uveitis is an under-diagnosed and under-recognized medical condition that causes vision impairment, ocular pain, and loss of vision. Uveitis affects younger people – the median age group of patients is 35-39 – and is in many cases a chronic condition. Experts estimate that 10% of new cases of blindness in the United States are caused by this disease. Approximately 300,000 people suffer from uveitis in the United States alone, roughly 50% of whom are affected by anterior uveitis. The only therapeutic class approved by the FDA for treatment of uveitis is corticosteroids. Chronic oral corticosteroids, even at doses of 10 mg/day, are burdened with multiple side effects, such as osteoporosis, hypertension, hyperglycemia, hypercholesterolemia, impaired wound healing, weight gain, cosmetic effects, and mood disorders. As a result, current treatment guidelines suggest a goal of reducing systemic corticosteroid use to a prednisone equivalent of 10mg/day or less. Of note, chronic use of local corticosteroids applied to the eye, while avoiding the severe metabolic disturbances associated with systemic exposure, lead frequently to severe side effects in the eye, most notably glaucoma and cataract formation.

Treatment of uveitis depends on several factors including: anatomic location (anterior, intermediate, posterior), disease severity, and laterality (unilateral vs. bilateral). Corticosteroids (topical, periocular via injection, intraocular, via injection or implant, or systemic) are used frequently to control the inflammation acutely and chronically. In many patients, however, the severity of disease and/or the need for high doses of corticosteroids provides the basis for the use of immune suppressive drugs (corticosteroid-sparing agents) to reduce or avoid the use of corticosteroids altogether. Anti-metabolites, T-cell inhibitors, and alkylating agents are among the corticosteroid sparing agents, although none of these are currently FDA-approved for this indication. The therapy is typically individualized and requires regular monitoring to avoid adverse effects.

Lux Biosciences has exclusively licensed voclosporin, a next-generation calcineurin inhibitor, for ophthalmic use and is developing an oral form of the molecule, Luveniq™, for sight threatening, non-infectious uveitis. The Phase 3 LUMINATE research studies (Luveniq Uveitis Multicenter Investigation of a New Approach to TrEatment) have been completed and are encompassing 558 patients worldwide. If approved by FDA, this product would represent the first steroid-sparing product for the treatment of uveitis available in the United States.

The Market Opportunity: There is a major need for a safe, effective, and approved medication in uveitis that allows tapering or eliminating corticosteroids. Between North America and Europe, there are approximately 500,000 patients affected by non-infectious (autoimmune) uveitis, of which about half may not be controlled by intermittent topical corticosteroid treatment. This is the target group for Luveniq. While currently, several corticosteroid-sparing agents are used experimentally, none of these has been thoroughly tested and approved (with the exception of cyclosporine A in Germany and a few other countries). The dearth of available treatment options is comparable to rheumatoid arthritis in the early 1990’s, before the advent of novel medications. Rheumatoid arthritis and uveitis share other similarities:

• both are autoimmune diseases, resulting in chronic inflammation of the affected organ/tissue leading to severe, degenerative conditions unless treated aggressively;

• both are often associated with other autoimmune diseases, such as psoriasis;

• both are, in principle, amenable to similar types of treatments, directed at activated immune cells
  (Th-1 and Th-17); and

• both are relatively rare, affecting less than 1% of the population.

However, while the rheumatoid arthritis market has experienced major growth – from approximately $100M worldwide in 1990 to approximately $7B in 2006 – behind novel and effective medications, the uveitis market remains small and lacks innovation. Lux Biosciences believes that the uveitis market may experience major growth with the advent of novel and effective medications. In addition, a novel, corticosteroid-sparing medication has the potential to establish a new standard of care for this potentially debilitating condition.