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REJECTION IN Corneal Transplantation

The Disease: Approximately 32,000 corneas are transplanted each year in the United States and an additional 22,000 in Europe. The prevalence of cornea transplant recipients is estimated to be about 350,000 in the United States and Europe. While the cornea is generally a tissue that is not vascularized -- does not contain blood vessels -- and thus is less prone to acute rejection, up to a third of all patients are at increased risk of immune-mediated rejection reactions and ultimately graft loss.

The most common diagnoses leading to the transplantation of a donor cornea include: pseudophakic bullous keratopathy (PBK), Fuchs’ dystrophy, keratoconus, corneal scarring and aphakic bullous keratopathy (ABK). Recent long-term studies report 10-year corneal graft survival rates of 59%-80%. However, in the high-risk group, as reported in the literature, the 10-year graft survival rate is only about 40%, far lower than kidney transplants (70%).     

In addition, the cumulative rate of graft failures by way of loss of endothelial cells and clouding of the graft is significant despite relatively high survival rates. 

The leading causes of graft failure following initial transplantation include rejection (27.9%), endothelial rejection without immunological reaction (30.1%) and ocular surface disease (18.0%). It has been postulated that there is also a group of patients who may experience sub-clinical rejection.  In addition to the risk of graft loss, rejection episodes lead to the irreversible loss of cells in the cornea resulting in a loss of corneal clarity and sight for the patient. Hence, it is imperative to prevent rejection reactions – even if mild – as these are major risk factors for severe rejection and graft loss.

The postoperative management of patients at increased risk for graft loss due to immunological causes varies.  In the United States, corneal transplantation is usually an outpatient procedure and consequently, topical corticosteroids are used commonly while the use of systemic corticosteroids and immunosuppressive agents are limited.  In Europe, on the other hand, physicians use systemic immunosuppressive medications more frequently following corneal transplantation in patients at increased risk for rejection. In cases of severe graft rejection, intravenous corticosteroids may be used.

Lux Biosciences has licensed LX201 from the National Eye Institute (National Institutes of Health) and is currently enrolling patients into a Phase 3 clinical trial. Details of the LUCIDA (LUx Corneal Transplant Implant Development and Advancement of Therapy) clinical trials can be found at www.clinicaltrials.gov.

The Market Opportunity: Although currently under-recognized, the prevention of rejection reactions in cornea transplant recipients is a therapeutic imperative. Nothing is currently approved; however, common clinical practice is to dose topical corticosteroids frequently (up to ten times a day) initially after the transplant surgery, and taper the frequency of dosing. Experimentally, topical or systemic immunosuppressive medications are also employed.

The number of corneas transplanted each year corresponds approximately to all solid organs combined. High-risk cases represent approximately up to a third of all corneas transplanted every year, approximately 10,000 in the United States. In addition, it is estimated that over 50,000 high-risk patients have previously received a transplant. The high medical need coupled with the anticipated chronic nature of the condition is likely to create a significant market opportunity. A product that in addition to efficacy and safety is also independent of patient compliance by providing long-term therapeutic levels of immunosuppressive drug would appear to address the medical need optimally.