Ocular graft-versus-host disease (O-GVHD) is a particularly severe and debilitating complication of allogeneic hematopoietic stem cell transplantation (HSCT). O-GVHD develops in 60-90% of patients with chronic GVHD. Currently, Restasis (cyclosporine A, 0.05%) is the only FDA approved prescription topical medication to treat O-GVHD. In 2012, Restasis had sales of just under $1 billion for the treatment dry eye; however, the therapeutic efficacy of Restasis is only ~15%, and its use is associated with a 17% rate of adverse events. This lack of robust clinical effectiveness demonstrates that alternative therapies are needed. Many HSCT patients who fail Restasis therapy have found relief from using autologous serum formulated into topical eye drops (autologous serum tears, AST). Unfortunately, the lack of standardization of AST preparations (which are often prepared in doctor's offices or pharmacies), and challenges with its storage and administration, have limited widespread adoption of this product. In order to address the drawbacks of AST, we have developed a proprietary method to manufacture a promising alternative: a standardized platelet lysate preparation using pooled platelet collections (phPL) from qualified blood donors (Elate-OcularTM; Ocular-phPL). We believe Elate- OcularTM will be superior to Restasis or AST for treatment of patients with O-GVHD and other forms of dry eye since Elate-OcularTM is enriched (compared to serum) for a number of growth factors that promote corneal healing, has robust anti-inflammatory actions that can reduce ocular inflammation in patients with GVHD, and possesses bacteriostatic properties. This STTR Phase I application is submitted by Cambium Medical Technologies LLC, a start-up company founded by 4 faculty members from Emory University School of Medicine who developed Ocular-phPL. Emory will be the sub-contracting research organization for this application. Emory University has filed a patent application to protect our proprietary manufacturing process for phPL, and Cambium has exclusive rights to this patent and technology. The investigators have previously received two INDs from FDA CBER for other applications of phPL (IND14825-NCT01659762 and IND16191- NCT02359929), and we are now seeking to submit a treatment IND for Elate-OcularTM and conduct a Phase I/II clinical study in HSCT patients with O-GVHD. In order to support these clinical studies, we propose in this application to first further improve and validate the safety and efficacy profiles f Elate-OcularTM by: (i) demonstrating feasibility of applying a pathogen inactivation (PI) process during production of Elate- OcularTM; (ii) performing in vitro work on Elate-OcularTM (+/- PI treatment) to compare product compositions and mechanisms of action; and (iii) performing animal toxicology/efficacy studies with Elate-OcularTM (+/- PI treatment) in animals with a pre-existing inflammatory condition or deficient tear production. Successful completion of these aims will allow us to complete our FDA IND application and initiate the Phase I/II study (for which we will seek Phase II STTR support) in order to demonstrate that Elate- OcularTM is safe and well-tolerated in patients suffering O-GVHD morbidity, a required step toward future commercialization.
Many patients with blood cancers are increasingly being treated by allogeneic hematopoietic stem cell transplantation (HSCT). This type of HSCT is often curative, but is not without side effects including debilitating eye problems. We propose to perform the FDA-required studies necessary to commercialize a new eye drop designed to treat the ocular side effects of allogeneic HSCT.
