Despite tepid investor response to safety data from the latest comparative trial of its lead-candidate glaucoma agent, Aerie Pharmaceuticals says it is still on track to file a New Drug Application for the agent in the third quarter of this year.
However, investors focusing on that data, from the Rocket 1 and 2 trials, may be missing another story about Aerie: weeks earlier the same group of investigators reported encouraging short-term results for a combination of Aerie’s lead agent, Rhopressa (netarsudil), a small-molecule Rho kinase inhibitor, with latanoprost that showed superior efficacy at lowering intraocular pressure (IOP) than either drug used individually.1
Investigators presented results of the Rocket 1 and 2 Phase III trials at the America Glaucoma Society (AGS) meeting earlier this month.2 The topline results showed that AR-13324 0.02% ophthalmic solution, otherwise known as Rhopressa, in both daily and twice-daily dosing was non-inferior to timolol 0.5% twice-daily in lowering IOP. Twice-daily dosing with Rhopressa had a greater IOP-lowering effect, but also had a higher rate of discontinuation due to adverse events.
And it’s those adverse events that have, as the Street’s Adam Feurstein put it, “spooked” investors. Aerie declined to make any additional comment on the Rocket 1 and 2 results.
Specifically, Rocket 2 found the overall rates of adverse events – mostly mild to moderate hyperemia – were around 65% in the once-daily Rhopressa group and 78% in the twice-daily group versus 25% in the twice-daily timolol group. The disparity in adverse events was even more pronounced in Rocket 1, which compared only once-daily Rhopressa with twice-daily timolol: 67% versus 16.3%, respectively.
However, the AGS poster also noted that the hyperemia was mild to moderate and episodic over the course of the studies, and the mean hyperemia score was around 0.5, with a score of 1 representing mild hyperemia. The events “were mostly mild, resolved without treatment, and generally did not lead to patient discontinuation,” the Rocket 1 and 2 authors stated.
Aerie’s stock dropped around 10% the day of the Rocket 1 and 2 announcement and has lost ground steadily since, closing at around $12 last Friday from a high of $17.63 the day before the study results came out. On Monday it showed signs of a rebound.
Drilling down into the Rocket 2 findings comparing once-daily Rhopressa with twice-daily timolol, the following adverse events were reported (Rhopressa vs. timolol):
- Conjunctival hyperemia (50.2% vs. 10.8%).
- Conjunctival hemorrhage (14.7% vs. 0%).
- Corneal deposits (8.8% vs. 0.4%).
- Blurred vision (7.2% vs. 2.8%).
- Increased tearing (4.8% vs. 0%).
- Reduced visual acuity (4.4% vs. 1.6%).
- Ocular pruritus (4.8% vs. 0%).
- Lid erythema (4.8% vs. 0.8%).
- Conjunctival edema (1.6% vs. 0%).
In a conference call with investors March 1, Aerie chairman and CEO Vicente Anido Jr., PhD, said the company is still on track to file a New Drug Application for Rhopressa 0.02% in the third quarter of 2016.
Meanwhile, Mercury 1, the first Phase III clinical trial for Roclatan 0.02%, the Rhopressa 0.02%/latanoprost 0.005% combination therapy, is proceeding forward and its 90-day topline interim efficacy readout is on track for the third quarter this year, Aerie said in a statement. Mercury 2, the second Phase III clinical trial for Roclatan, was due to commence last month.
Early Mercury 1 results showed that 69% of patients on Roclatan 0.02% achieved IOP reduction of 18 mm Hg at day 29 versus 47% on latanoprost 0.005% only and 39% on Rhopressa 0.02% only.1 However, the disparity of adverse events between Roclatan 0.02% and latanoprost 0.005% only was similar to that between Rhopressa and timolol in the Rocket 2 study: 75.3% versus 32.9%, respectively. Yet, the rates of ocular infections were significantly lower for Roclatan 0.02%: 2.7% versus 5.5% for latanoprost alone. Again, reports of hyperemia were typically mild, the Mercury 1 authors reported.
Last year, the same investigators reported disappointing results of a comparative trial of once-daily Rhopressa in 0.01% and 0.02% concentrations versus once daily latanoprost 0.005% in lowering IOP.3 Rocket 4, the Phase III clinical trial for Rhopressa in Europe, remains on schedule for topline 90-day efficacy readout in the fourth quarter this year, the company said.
Aerie has $150.4 million in cash, cash equivalents and investments on the balance sheet. In 2015, net cash burn, excluding financing activities, totaled $59 million, slightly better than the guidance the company previously provided.
- Lewis RA, Levy B, Ramirez N, C Kopczynski C, Usner DW, Novack GD; PG324-CS201 Study Group. Fixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomised, controlled study in patients with open-angle glaucoma or ocular hypertension. Br. J. Ophthalmol. 2016;100:339–344.
- Bacharach J, Heah T, Ramirez N, Kopczynski CC, Novack GD, for ROCKET 1 and ROCKET 2 Study Group. AR-13324 ophthalmic solution 0.02%: topline results of two phase 3 clinical studies in patients with open angle glaucoma and ocular hypertension. Poster presented at the American Glaucoma Society, March 3, 2016.
- Bacharach J, Dubiner HB, Levy B, Kopczynski CC, Novack GD; AR-13324-CS202 Study Group. Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure. Ophthalmology 2015;122:302–307.