Results Also Suggest a Potential New Mechanism of Action
Aerie Reaffirms Timeline to Commence Two Phase 3 Studies by mid-2014
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 study subjects had IOPs in the normotensive range of 12 to 21 mmHg, with an average diurnal IOP for the group of approximately 16 mmHg prior to dosing. After eight days of dosing, once-daily administration of AR-13324 reduced the average diurnal IOP to approximately 11 mmHg, representing a decrease of approximately 5 mmHg, or over 30 percent.
"As documented in the Baltimore Eye Survey2, patients with
low-to-moderately elevated IOPs at the time of diagnosis represent the
significant majority of glaucoma patients," stated
As background, IOP is determined by the contributions of four distinct MOAs: aqueous humor (eye fluid) production, resistance to aqueous outflow via the trabecular meshwork and uveoscleral pathway, and episcleral venous pressure. Historical studies have shown that episcleral venous pressure accounts for approximately half of IOP in normotensive subjects and approximately one-third of IOP in patients with pressures of 24 to 30 mmHg. When episcleral venous pressure is lowered, aqueous humor is able to flow more freely from the eye. Aerie plans to conduct additional studies to directly measure the effect of AR-13324 on episcleral venous pressure and better understand this potential new mechanism of action.
AR-13324 Clinical Program
Aerie's successful 28-day Phase 2b trial demonstrated that once-daily
administration of AR-13324 produced significant IOP lowering in the
range of 5.7 to 6.2 mmHg in patients with elevated IOP, with a
differentiated efficacy profile of consistent IOP lowering across all
baseline IOPs tested in the clinical trial. The multiple mechanisms of
action for AR-13324 include increasing fluid outflow through the
trabecular pathway or primary drain, reducing fluid production, and
potentially also lowering episcleral venous pressure. Aerie plans to
commence two Phase 3 registration trials of AR-13324 in mid-2014, with
total expected enrollment of approximately 1,200 patients. Based on the
Phase 2b clinical trial results, previous discussions with the
Assuming the registration trials commence on schedule, three-month efficacy results are expected to be released in mid-2015, and should the trials be successful, Aerie expects to submit an NDA filing for AR-13324 by mid-2016.
PG324 Clinical Program
PG324 is a once-daily eye drop that combines AR-13324 with latanoprost, a prostaglandin analogue that is the most widely prescribed glaucoma drug. If approved, Aerie believes that PG324 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 also lowering episcleral venous pressure. The Company believes that PG324, if approved, would be the only glaucoma product that covers the full spectrum of IOP-lowering mechanisms, thereby providing a greater IOP-lowering effect than any currently approved glaucoma product.
Aerie is preparing to bring PG324 into a 28-day Phase 2b clinical trial 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.
2 Sommer A, Tielsch JM, Katz J et al. Relationship between
intraocular pressure and primary open angle glaucoma among white and
black Americans: The
Aerie is a clinical-stage pharmaceutical company focused on the discovery, development and commercialization of first-in-class glaucoma therapies. The Company is preparing for two Phase 3 registration trials, where the primary efficacy endpoint will be to demonstrate non-inferiority of IOP lowering for AR-13324 (dosed once daily) compared to timolol (dosed twice daily). The Company also is preparing for a Phase 2b clinical trial of its fixed-dose combination product PG324, where the primary efficacy endpoint will be to demonstrate superiority of PG324 to each of its components.
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outlook, analyses or current expectations concerning, among other
things: the success, timing and cost of our ongoing clinical trials and
anticipated Phase 3 and Phase 2b clinical trials for our current product
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completion of the trials; the timing of and our ability to obtain and
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