Belgium-based clinical stage ophthalmology firm Amakem Therapeutics has dosed first patients in a Phase II dose-ranging trial of its drug candidate, AMA0076, for treatment of glaucoma.
Based on the company’s localised drug action platform, AMA0076 is a highly potent locally-acting Rho Kinase (ROCK) inhibitor designed to reduce intraocular pressure (IOP) by acting specifically on the main outflow system in the eye while minimising side effects such as hyperemia (red eye).
Hyperemia is a particularly problematic side-effect leading to patient non-compliance that has been seen with all other ROCK inhibitors developed for glaucoma.
Approximately 80 patients in the US are expected to be enrolled in the Phase II study with an optimised formulation of AMA0076 applied topically as eye-drops.
The trial’s primary efficacy endpoint will be change in IOP from baseline at the end of 28 days of treatment and secondary endpoints include IOP assessment at other time points as well a safety and tolerability assessments.
Previously, AMA0076 showed IOP reduction without significant hyperemia in a first-in-human trial in patients with glaucoma and ocular hypertension.
The company said that an optimised formulation with significantly improved corneal absorption led to substantial IOP reduction with no significant hyperemia in a subsequent Phase Ib trial.
Amakem chief executive officer Jack Elands said AMA0076 has showed IOP reduction without significant hyperemia, the first ROCK inhibitor to achieve this goal in the clinic.
"The experience we gained in our first-in-human study and the subsequent clinical evaluation of our new formulation gives us great confidence as we begin this dose-ranging study," Elands said.
The company intends to report top line results from the multicentre, randomised, double-masked, placebo-controlled trial in the fourth quarter of 2014.
Amakem chief medical officer Steve Pakola said glaucoma remains a significant cause of vision loss and blindness and affects many millions of people worldwide.
"Using ROCK inhibition to increase the outflow of aqueous humor from the eye represents a target for glaucoma therapy whose promise is widely recognised," Pakola said.
"However, development has been held back by the side-effect profile of ROCK inhibitors, particularly hyperemia.
"In AMA0076, we believe we have a candidate that can fully harness the potential of this mechanism of action and thereby provide a potential treatment alternative for this prevalent and serious condition where current treatments do not address the needs of many patients."
Image: Conjunctival vessels dilated at the corneal edge and hazy cornea characteristic of acute angle closure glaucoma. Photo: courtesy of Jonathan Trobe.