Amakem NV, a kinase platform company focusing on ophthalmology, has initiated a phase IIa proof of concept study of its novel Rho Kinase (ROCK) inhibitor, AMA0076, in patients with glaucoma and ocular hypertension. The start of the study follows Amakem’s receipt of Investigational New Drug Application (IND) approval from the United States Food and Drug Administration (FDA).

AMA0076 is a highly potent ROCK inhibitor and is based on Amakem’s ‘Localized Drug Action’ platform, which generates novel kinase inhibitors that minimize the risk of systemic as well as local side effects such as hyperaemia.

The study is a multi-centre, randomized, double-masked, placebo-controlled dose-escalation study with AMA0076 applied topically, as eye drops. First patients have initiated treatment in this 80 patient clinical trial with six participating centres in the United States (ClinicalTrials.gov identifier NCT01693315).

The primary efficacy endpoint will be reduction in intraocular pressure (IOP), which is a major factor in the pathology of glaucoma, after two and four weeks of dosing. A number of secondary efficacy endpoints will be used to further analyze the impact of AMA0076 on IOP. The company expects to report top line results in 2013.

AMA0076 is aimed at providing better patient outcomes than other ROCK inhibitor based treatments currently in development because its improved side effect profile enables higher dosing, leading to better efficacy. Pre-clinical studies have shown that AMA0076 highly effectively lowers IOP in relevant models, with a magnitude of IOP reduction exceeding that of the current leading glaucoma treatment latanoprost. Importantly, AMA0076 has been shown to avoid hyperaemia, also known as ‘red eye’, which is seen as a major dose limiting side effect for other ROCK inhibitors in development.

Dr Jack Elands, CEO of Amakem, said: “Today’s announcement is a major milestone for Amakem. With our first product entering the clinic we expect to validate our Localized Drug Action platform. Conceived and developed by the company’s founder and CSO, Dr Dirk Leysen, this platform allows the development of novel drugs in ophthalmology and other indications, by harnessing the power of kinase inhibition while managing potential side effects. It is very satisfying to have progressed AMA0076 within 20 months from discovery into its first clinical trial and to the point where we believe we will further demonstrate the potential of our platform to create valuable new therapeutics.”

Dr Steve Pakola, chief medical officer of Amakem, said: “Glaucoma affects many millions of people and remains a significant cause of vision loss and blindness. Existing treatments are not effective for all patients and while the potential of ROCK inhibitors to reduce IOP has been recognized, their development has been held back by their side effect profile, particularly hyperaemia which is distressing for patients and reduces compliance. We look forward to confirming in the clinic the highly promising results we have seen so far with AMA0076 and to advancing what we believe has the potential to be a valuable new treatment option for glaucoma patients.”