Who needs primary endpoints anyway? Aerie touts silver linings from failed PhIIb, plots PhIII in dry eye disease
Aerie’s dry eye disease drug may not have met the primary endpoints it’s chosen for a Phase IIb study, but that’s not stopping the biotech from powering through Phase III — and steering toward a field with plenty of rivals.
“While we did not achieve statistical significance at our pre-determined primary endpoints at Day 28, as a reminder, this is a Phase 2b study where selecting primary endpoints are not required,” CEO Vicente Anido said in a statement.
Instead, he highlighted how AR-15512, a TRPM8 agonist given in the form of an eye drop, spurred statistically significant improvements on “multiple FDA-recognized symptoms and signs” — things like ocular discomfort, tear production and eye dryness.
All of that, he added, points to a clear path toward approval.
Investors aren’t so sure. Shares $AERI fell 17.83% after the bells to $2.80.
Based on the results, execs have decided to bring the higher concentration of 0.003% BID into two Phase III trials that will stretch over three months.
With Novartis’ blockbuster Xiidra already on the market, the FDA is in no rush to clear new treatments for dry eye disease, rejecting Kala’s initial NDA and demanding a new Phase III before finally approving its ocular corticosteroid, Eysuvis. But biotechs have argued that the market remains untapped and there’s still need for more options.
A total of 369 patients enrolled in the COMET-1 study into one of three arms: AR-15512 (0.0014%), AR-15512 (0.003%) or AR-15512 vehicle. Dosed daily over 84 days, they were evaluated at days 1, 14, 28 and 84.
Unusual for a data readout, Aerie didn’t provide a p-value on the primary endpoints — or even mention them — for the topline. According to its posting on clinicaltrials.gov, the primary outcome measures of the COMET-1 study are improvement from baseline in ODS-VAS, or ocular discomfort score on a visual analogue scale, and improvement on the anesthetized Schirmer’s score. There was no word on how patients fared on those two metrics in a press release.
Instead, the company highlighted how the drug cleared the bar for ocular discomfort at day 84 (p=0.028), SANDE (symptom assessment in dry eye) at days 14, 28 and 84 (p-value between 0.025 and 0.0005) and eye dryness at day 84 (p=0.03). It also reported positive results in signs like efficacy after the first dose, tear production based on the unanesthetized Schirmer’s score, conjunctival redness and ocular surface staining.
Less than 3% of participants discontinued the trial due to adverse events, Aerie added, and they concluded both formulations tested were safe and well-tolerated.
Aerie will see what the FDA thinks of its plan in an end of Phase II meeting planned for early next year — although the rest of the world may not find out until much later.
AR-15512 came to Aerie — which already boasts of several approved drugs in glaucoma — via its 2019 buyout of Spain’s Avizorex Pharma. The upfront payment came in at $10 million, perhaps reflecting the sales expectation.“We would look for AR-15512 to match the efficacy of approved dry eye disease therapeutics (in terms of both dry eye disease signs and symptoms) with peak sales of ~$230 mil (indication would be worth $4). If efficacy is significantly above on-market products, our peak sales estimates could be ~$500 mil (indication would be worth $9),” Mizuho analysts wrote in a recent note.