Aerie Pharmaceuticals Reports Positive Results for Lead Candidate AR-13324 in Normotensive Individuals
Aerie Pharmaceuticals, Inc., announced top-line results from the company’s recently completed phase 1 pharmacokinetics (PK) study. AR-13324 eye drops were administered once daily to 18 healthy individuals over an 8-day period to assess systemic exposure to the drug, according to a company news release. In addition to the primary PK outcome of the study, the drug’s effect on IOP was also measured.
According to the news release, the PK results demonstrated very low systemic exposure to the drug, with blood levels at or below the limit of detection of 0.1 ng/mL at all time points. In addition, there were no drug-related effects on systemic safety parameters such as blood pressure and heart rate. All subjects had IOPs in the normotensive range of 12 to 21 mm Hg, with an average diurnal IOP of 16 mm Hg before dosing. After 8 days of dosing, once-daily administration of AR-13324 reduced the average diurnal IOP to approximately 11 mm Hg, representing a decrease of approximately 5 mm Hg or over 30%.
“The large reduction in IOP achieved by AR-13324 in normotensive individuals distinguishes AR-13324 from currently available glaucoma drugs, which are typically less effective in subjects with low baseline IOPs,” Brian Levy, OD, MSc, chief medical officer of Aerie, said in the news release. “Preclinical normotensive animal studies have shown similar results. These data are consistent with the results of our previous phase 2b clinical trial in which AR-13324 demonstrated consistent IOP lowering irrespective of baseline IOP, whereas the comparator latanoprost demonstrated reduced efficacy at lower baseline IOPs, as disclosed in our recently filed registration statement.”
“Very commonly, glaucoma patients require a low normal IOP to prevent further progression, and a drug that could achieve this would be a great advance,” David Epstein, MD, chairman of Aerie’s scientific advisory board, said in a news release. “I am encouraged by the recent data and previous clinical findings for AR-13324 and believe that its significant IOP-lowering effect at lower baseline IOPs could reflect an additional mechanism of action beyond the dual mechanisms of which we are already aware, one that could involve the reduction of episcleral venous pressure.”
The multiple mechanisms of action reported for AR-13324 include increasing fluid outflow through the trabecular pathway, reducing fluid production, and potentially also lowering episcleral venous pressure. Aerie said it plans to commence two phase 3 registration trials of AR-13324 in mid-2014 involving approximately 1,200 patients. Based on the results of the phase 2b clinical trial, previous discussions with the FDA, and the recent findings on the potential new mechanism of action, the company plans to recruit patients into the phase 3 clinical trials with baseline IOPs ranging from 21 to 26 mm Hg. The trials will measure efficacy over 3 months and safety over 12 months. The primary efficacy endpoint of the trials will be to demonstrate noninferiority of IOP lowering for AR-13324 (dosed once daily) compared to timolol (dosed twice daily).
Aerie’s other drug candidate, PG324, is a once-daily eye drop that combines AR-13324 with latanoprost. According to the news release, the company is preparing a 28-day, phase 2b clinical trial of PG324 that is expected to include approximately 300 patients and will compare two concentrations of PG324 to latanoprost and to AR-13324, all dosed once daily. The efficacy endpoint will be superiority of PG324 to each of its components. Results of the PG324 phase 2b trial are currently expected in mid-2014.