US-based Aerie Pharmaceuticals has dosed its first patient in a phase 2b trial of PG324, a novel, fixed-combination of its AR-13324 and latanoprost, a prostaglandin analogue that is the most widely prescribed glaucoma drug.
About 300 patients with glaucoma or ocular hypertension will be enrolled in the 28-day trial, which will compare two concentrations of PG324 to latanoprost and to AR-13324, all dosed once daily.
The efficacy endpoint in the trial will be superiority of PG324 to each of its components, as measured by the lowering of mean diurnal intraocular pressure (IOP) on day 28 compared to baseline.
According to the company, top-line results of the phase 2b trial are expected to be released in mid-2014.
Aerie chief medical officer Brian Levy said: "Aerie's phase 2b trial of PG324 is based on substantial and compelling results we have achieved with our lead candidate, AR-13324, as well as preclinical proof of concept studies for PG324.
"In addition to our recent positive AR-13324 phase 1 findings, including reductions in IOP in individuals who are normotensive, previous phase 2b testing of AR-13324 demonstrated significant IOP lowering in the range of 5.7mmHg to 6.2mmHg in patients with elevated IOP, with consistent IOP lowering across all baseline IOPs tested in the clinical study.
"We believe that adding latanoprost to AR-13324 in our fixed-combination product has the potential to provide for maximal IOP lowering in patients with glaucoma and ocular hypertension, by targeting all currently known mechanisms of action that affect intraocular pressure."
The company believes that if PG324 is approved, it would be the first glaucoma product to lower IOP through potentially four mechanisms of action: increasing fluid outflow through the trabecular pathway or primary drain, increasing fluid outflow through the uveoscleral pathway or secondary drain, reducing fluid production in the eye and potentially lowering episcleral venous pressure.
If approved, PG324 is also expected to cover the full spectrum of these IOP-lowering mechanisms, thereby providing a greater IOP-lowering effect than any currently approved glaucoma product.
Aerie chairman and CEO Vicente Anido said: "Aerie has been at the forefront of understanding the unmet needs in glaucoma and exploring new mechanisms of action to effect greater reductions in IOP, which ultimately can help protect and maintain patients' vision.
"Looking forward, we have an aggressive development timeline, with the expectation that in the next 18 months, in addition to reporting the results of our PG324 phase 2b trial, we will also report phase 3 efficacy data from our AR-13324 programme and will have achieved phase 3 readiness for PG324.
"With full ownership of these novel products, including IP protection that runs through at least 2030, we are in a very strong position to maximise the value of these programmes and further advance toward potential regulatory review and commercialisation."
Image: Photo showing conjunctival vessels dilated at the corneal edge (ciliary flush, circumcorneal flush) and hazy cornea characteristic of acute angle closure glaucoma. Photo: courtesy of Jonathan Trobe.