Aldeyra Therapeutics, Inc. announced that its phase 3 trial evaluating 0.25% reproxalap ophthalmic solution for the treatment of dry eye disease (DED) has achieved its primary endpoint.
This comes as a major win for the company, which previously faced FDA concerns over the investigational candidate in 2023 after submitting a new drug application (NDA) for that same indication in 2022.
Let’s start with a refresh on reproxalap.
What it is: Aldeyra’s first-in-class, small-molecule modulator of reactive aldehyde species (RASP).
- Note: RASP is known to be elevated in ocular and systemic inflammatory disease as well as cause decreased tear production, eye redness, change in lipid tear composition, and increased ocular inflammation
- Learn about the company’s RASP modulator platform
Its efficacy: Previous clinical data has shown reproxalap to demonstrate signs of activity ranging from within minutes of administration to up to 12 weeks.
Take note: The candidate is also in clinical development for the treatment of allergic conjunctivitis.
And its regulatory background for DED?
Here’s an abbreviated rundown:
In October 2023 (8 months after the FDA accepted Aldeyra’s NDA), the federal agency identified substantive review issues following a late-cycle review meeting with the company on phase 3 and 12-month clinical trial data for reproxalap.
Then in November 2023, the FDA sent Aldeyra a complete response letter with a list of its concerns over the clinical evidence intended to support reproxalap’s DED clinical adequacy.
Fast forward to April 2024, the company announced plans to resubmit its NDA for reproxalap as well as initiate a phase 3 dry eye chamber clinical trial (our current topic of discussion).
- The reason for this: To fulfill the FDA’s request for at least one additional study demonstrating reproxalap’s positive effect on dry eye ocular symptoms.
Which brings us to now?
Indeed. Here’s what to know about this trial:
- The design: randomized, double-masked, vehicle-controlled dry eye chamber study
- The participants: 132 DED patients
- Note: All were randomized to receive either reproxalap or vehicle before and during exposure to an additional dry eye chamber.
- Reproxalap group (n = 66)
- Vehicle group (n = 66)
- Note: All were randomized to receive either reproxalap or vehicle before and during exposure to an additional dry eye chamber.
- The primary endpoint: ocular discomfort
- Based on previous clinical data that found ocular discomfort in the dry eye chamber after reproxalap treatment was statistically lower than vehicle (p = 0.0003).
Now talk about this positive data.
Aside from achieving its sole primary endpoint—ocular discomfort, an FDA-accepted DED symptom, from 80 to 100 minutes in the dry eye chamber—reproxalap was also observed to be well tolerated, according to Aldeyra.
As with previous clinical findings, the most commonly reported adverse event was mild and transient instillation site discomfort.
Further: No treatment-related discontinuations occurred among participants.
And the significance of this?
In regards to these findings, the company noted reproxalap to be “the first investigational drug with pivotal data supportive of acute and chronic activity in reducing (DED) symptoms.”
Its uniqueness also extends to it being the first drug “for chronic administration with pivotal data supportive of acute activity in reducing ocular redness.”
Lastly, what’s the timeline for next steps?
Aldeyra reported that a potential resubmission of reproxalap’s DED-targeted NDA is expected before the end of 2024—and once that occurs, the FDA’s review period will extend an additional 6 months.