Aldeyra Therapeutics released topline results from its phase 3 clinical trial assessing 0.25% reproxalap ophthalmic solution (reproxalap) for the treatment of allergic conjunctivitis.
Refresh me on the company.
Aldeyra Therapeutics is a biotechnology company focused on developing pharmaceutical therapies for treating immune-mediated diseases. In lieu of directly blocking or activating single-protein targets, these therapies are designed to modulate immunological systems while simultaneously optimizing multiple pathways and limiting toxicity.
And reproxalap?
The investigational new drug candidate is Aldeyra’s first-in-class, small-molecule modulator of reactive aldehyde species (RASP).
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.
To note, the FDA accepted a new drug application (NDA) for reproxalap earlier this year.
How quickly can it work?
Per previous study data, reproxalap has illustrated signs of activity ranging from within minutes of administration to up to 12 weeks.
What other research is there on it?
Earlier this year, Aldeyra reported positive topline data from a 12-month safety trial of reproxalap for the treatment of dry eye disease (DED).
Gotcha. So tell me about this phase 3 trial.
The single center, randomized, double-masked, vehicle-controlled, two-way crossover design allergen chamber phase 3 INVIGORATE-2 trial (NCT05234554) (quite a mouthful … I know) enrolled 131 patients (ages 18+) diagnosed with allergic conjunctivitis at least 2 years prior.
And the dosages?
Patients were randomly administered a dose of reproxalap (twice) or a placebo (also twice).
What was measured?
The primary outcome included change from baseline in patient-reported ocular itching score (0-4 points cale) over a majority of 11 time points from 110 to 210 minutes following allergen chamber entry.
Secondary outcome was the change from baseline in ocular redness (0-4 point scale) over the allergen chamber duration (an estimated 3.5 hours).
Findings?
Compared to placebo-treated patients, the reproxalap-treated patients demonstrated a statistically significant reduction in ocular itching score across all 11 pre-specified primary endpoint comparisons (p < 0.001 for each).
Similarly, for the secondary endpoint, reproxalap patients exhibited a statistically significant reduction from baseline versus vehicle (p = 0.004).
What else for the secondary endpoint?
Change from baseline in patient-reported ocular tearing score (on a 0-3 point sale) as well as change from baseline in total ocular severity score (11-point compositie of itching, redness, and tear scores) also achieved statistical significance over the duration of the allergen chamber (p < 0.0001).
Did all patients complete the trial?
Actually, no. 130 out of the original 131 did though. To note, adverse events were not the reason for that patient’s discontinuation.
Speaking of adverse reactions …
Per Aldeyra, no safety or tolerability concerns were noted. However, the most common adverse event was mild and transient irritation at the instillation site.
Expert input?
According to Aldeyra President and CEO Todd C. Brady, MD, PhD, “We believe that the rapid-onset activity of reproxalap evidenced in the INVIGORATE clinical trials may offer hope to allergic conjunctivitis patients who are today not adequately treated, and also to dry eye disease patients, up to 50% of whom suffer from ocular allergy.”
So what’s next?
Next up is reproxalap’s target Prescription Drug User Act Date (PDUFA) of November 23, 2023.