Lexington, MA - November 8, 2012 - Inotek Pharmaceuticals Corp., a leader in the development of innovative drug candidates to address significant diseases of the eye, today announced that a multi-center, randomized, double-masked, placebo-controlled, dose-ranging Phase 2 clinical trial to evaluate the efficacy and safety of its novel eye-drop trabodenoson, also known as INO-8875, in patients with primary open-angle glaucoma or ocular hypertension successfully achieved its primary and secondary endpoints. The data were presented at the Ophthalmology Innovation Summit in Chicago, IL. Trabodenoson was found to reduce intraocular pressure (IOP) by approximately 7 mmHg at 28 days (p< 0.001) and was safe and well tolerated with very good ocular tolerability and less eye redness (hyperemia) than currently approved glaucoma treatments.
Trabodenoson is a first-in-class, highly selective A1 subtype adenosine mimetic for glaucoma and ocular hypertension that binds to epithelial cells in the trabecular meshwork, up-regulating gelatinases that clean out and remodel the meshwork, increasing outflow and restoring a healthier IOP.
“These Phase 2 trabodenoson results are highly encouraging, with the efficacy and safety data suggesting the potential for a glaucoma treatment with a profile superior to currently approved drugs,” said Rudolf A. Baumgartner, MD, Inotek’s Executive Vice President, Chief Medical Officer. “Additionally, based on pharmacodynamics observed in this study, we are also encouraged by the possibility of once-daily dosing, and look forward to exploring this profile in future trials.”
In the Phase 2 study, trabodenoson was found to be safe and well tolerated. Trabodenoson demonstrated: very good ocular and systemic tolerability; reduced hyperemia compared with the current first-line treatment for glaucoma, prostaglandin-based drugs; and no iris pigmentation. Patients receiving trabodenoson experienced IOP reductions of approximately 7 mmHg at 28 days (p-value < 0.001) and about one third of subjects had a response of 8 mmHg or greater. Based on the doses studied so far, the magnitude of IOP reduction is comparable to the efficacy range of prostaglandins, and superior to that of currently approved second-line therapies. Notably, efficacy was found to improve with duration of treatment, and a pharmacodynamic effect was present 24 hours after the last dose, signaling the potential for once-a-day dosing which will be evaluated in future studies.
“Trabodenoson is one of the most promising glaucoma drug candidates in development based on its novel mechanism of action, the safety and efficacy observed to date, and the potential for once-daily dosing.” commented Dr. Jonathan Myers, Director of Glaucoma Fellowship at the Wills Eye Institute. “It appears that trabodenoson works directly at the site most affected in glaucoma, the trabecular meshwork. In glaucoma, the meshwork loses its ability to let aqueous
humor pass easily out of the eye, and with trabodenoson the meshwork’s permeability to fluid is restored. If these data are born out in further clinical evaluation, trabodenoson could shift the paradigm of treatment for patients with glaucoma.”
“These data confirm our belief that trabodenoson has the potential to be a novel and important treatment option for patients,” said Paul G. Howes, President and Chief Executive Officer of Inotek. “Based on these very strong results, Inotek is planning a comprehensive late-stage clinical development program for trabodenoson, including trials that should complete Phase 2 development for trabodenoson as a first-line treatment, and trials to explore its efficacy in combination with a prostaglandin.”
The recently completed Phase II trial was a multi-center, randomized, double-masked, placebo-controlled, dose-ranging study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of trabodenoson delivered as an eye-drop formulation in patients with primary open-angle glaucoma or ocular hypertension. The trial enrolled 144 patients with IOP greater than or equal to 24 mmHg.
About Trabodenoson for Glaucoma
Glaucoma is a leading cause of blindness globally, and it is broadly accepted that lowering intraocular pressure (IOP) in patients with glaucoma is the only clinically reliable means of slowing the progression of vision loss. Current products for glaucoma, such as beta blockers and prostaglandins, lower IOP by reducing the flow of fluid into the eye or increasing its drainage through a secondary pathway in the eye – the uveoscleral pathway. However, as glaucoma advances with age, outflow through the eye’s trabecular meshwork becomes increasingly difficult as drainage channels narrow, and it is more difficult to lower pressure and slow vision loss only by increasing uveoscleral outflow. As a result, many patients do not respond adequately to the currently approved products, and up to 40% of patients are treated with a combination of products in the hope of achieving targeted reductions in IOP. There remains an unmet need for innovative glaucoma products acting on the pressure sensitive trabecular meshwork to provide improved IOP-lowering efficacy.
Trabodenoson has significant potential as an IOP-lowering medicine, either as monotherapy or in combination with other glaucoma products, because it restores the outflow of aqueous humor through the trabecular meshwork. As validation of its complementary mechanism to other glaucoma products, trabodenoson has shown substantial additivity of IOP-lowering efficacy when combined with the leading glaucoma medicine (latanoprost) in a preclinical model. As a highly selective adenosine-1 receptor agonist, trabodenoson has a novel mechanism differentiating it from currently approved products and other candidates in development for glaucoma in that it enhances an innate cellular signaling pathway to improve outflow through the trabecular meshwork.