After a brief and uncontentious advisory committee meeting, FDA approval for the Aerie Pharmaceuticals Inc. glaucoma drug Rhopressa (netarsudil) appears likely, setting the stage for the arrival of a new class of medicine to be used in addressing one of the leading risk factors for vision loss associated with the condition, elevated intraocular pressure (IOP).

Despite expressing concerns about common adverse events associated with the drug, the 10 voting members of the agency's Dermatologic and Ophthalmic Drugs Advisory Committee (ODAC) unanimously supported a statement in favor of the drug's efficacy in reducing elevated interocular pressure in patients with open-angle glaucoma or ocular hypertension. They also voted 9-1 in favor of its efficacy outweighing safety risks identified for the product. The meeting ended more than two hours ahead of its scheduled conclusion, a rarity, especially for an instance in which draft labeling was added to the roster of covered topics.

With a potential approval decision slated to arrive on Feb. 28, 2018, or earlier, Aerie CEO and Chairman Vince Anido told BioWorld that the company's manufacturing and commercial operations are ready to go, though it will need 90 days from receipt of an approval letter to field a sales force. If approved, the product would be priced at about $100 net per month, in the neighborhood of other current glaucoma medicines. Analyst opinions comprising a Cortellis consensus estimate forecast Rhopressa sales of $26 million in 2018, rising to $308 million by 2023.

The company's ODAC talking points emphasized the novelty of Rhopressa's mechanism of action as a Rho-associated protein kinase inhibitor thought to lower IOP by directly increasing fluid outflow through the trabecular meshwork, its compliance advantage as a once-daily eye drop vs. more common two or three times daily treatments, and its lack of measurable systemic absorption.

Phase III trials of Rhopressa compared it to the standard-of-care comparator timolol. Considering those studies, the FDA concluded that for trial participants with maximum baseline IOP of less than 25 mmHg, overall Rhopressa and timolol appeared to have similar mean IOP reductions on days 15, 43, and 90 of the studies. Though, for trial participants with higher maximum baseline IOP, or greater than 25 mmHg, netarsudil had smaller mean IOP reductions.

The most common ocular side effects in the phase III studies were conjunctival hyperemia, corneal verticillata, and conjunctival hemorrhage. As the first topical ophthalmic drug known to cause corneal verticillata – a whorl-like pattern of deposits typically localized to the basal corneal epithelium – much of the adcom's discussion gravitated to that topic. But, because its occurrence did not appear to affect visual function in any of the study patients, it appeared to be less a stumbling block to approval and more a necessary call-out in the labeling to prevent doctors from unnecessarily discontinuing treatment, as some did in one of the pivotal trials before the company fully appraised and communicated the issue to investigators.

Tonya King, a professor of biostatistics at the Pennsylvania State University College of Medicine, was the only panelist to express concern about Rhopressa's safety, lodging a 'no' vote on the question of whether its efficacy outweigh the safety risks. "Although the sponsor seemed to adequately discuss the severity of the adverse events, it seemed to me that the high discontinuation rate was still a concern."

Underscoring the significant lack of controversy associated with Rhopressa's NDA, no one offered comments about the application during a public comment period.

The FDA is not obligated to follow the voting recommendation of the advisory committee, but usually it does.

Following the adcom, company shares (NASDAQ:AERI) resumed trading after spending most of the days in halt. Shares fell 2.4 percent to $61.45, somewhat lower than a 52-week high of $66 reached upon the release of the adcom briefing documents. (See BioWorld, Oct. 12, 2017.)

Aerie has a second product candidate in the pipeline, Roclatan, a fixed-dose combination of netarsudil and latanoprost. It currently has two phase III registration trials underway, Mercury 1 and Mercury 2. In September, the company started patient dosing in Mercury 3, its European phase III trial of Roclatan. If these trials are successful, Aerie anticipates filing an NDA for Roclatan in late 2017 or early 2018.