麻豆传媒

The reactive aldehyde species (RASP) inhibitor reproxalap quickly and significantly increased tear production in patients with dry eye disease, according to a randomized trial reported at the American Society of Cataract & Refractive Surgery annual meeting.

In this exclusive 麻豆传媒 video, , of OCLI Vision in Garden City, New York, describes the study design and offers his takeaway on the results.

Following is a transcript of his remarks:

As a background, dry eye is a chronic, progressive multifactorial disease. It affects approximately 39 million Americans. And many Americans who have tried dry eye therapies have failed within the first year, highlighting that there is an unmet need for better new therapies.

Reproxalap is a novel investigational therapy and it targets RASP, which is a reactive aldehyde species, and we are investigating this for dry eye. And to understand RASP, RASP are basically upstream from the inflammatory cascade that many of us are familiar with. We're familiar with cytokines and T-cell activation, which are inhibited by corticosteroids and T-cell modulators like cyclosporine and lifitegrast. RASP is actually upstream of this, so it actually blocks prior to T-cell activation and cytokine formation, which reduces inflammation.

The study design was patients who had significant dry eye. They had to have corneal fluorescein staining of greater than four in at least one eye. And they had to have symptoms based on the visual analog scale of dry eye, and they had to have no tear use prior to the screening. The patients were tested in an environmental chamber and patients who did develop dry eye were enrolled in the trial. Patients' primary endpoints were Schirmer scores from baseline and Schirmer testing showing the number of patients who went above 10 mm of increased tear production. Secondary endpoints include things like redness and dryness and ocular discomfort.

There were 180 patients who received the vehicle and 180 patients who received the reproxalap. The patients were given the drops four times a day, one drop prior to entering the test chamber, one drop 45 minutes after chamber entry, and one dose on exit. And then we measured the dry eye symptoms and redness scales.

The baseline characteristics of the study, the patients were majority female, as you would expect with dry eye, and the median age in their low 60s.

The endpoints, which were statistically significant to a P value of 0.001, was that there was a significant increase in Schirmer scores in the patients who received their reproxalap versus the vehicle, and this was seen on day one. And change from baseline was 0.3 mm versus a reduction of 1.9 mm in the vehicle group.

When we looked at patients who had a 10-mm increase in Schirmer scoring based on responder analysis, there was 16% of patients versus 8% of patients in the control group. Again, a P value of less than 0.001.

The secondary endpoints, which were clinically significant, were the patients had a change from baseline in symptoms pre-chamber and post-chamber. All the other endpoints were not statistically significant.

Safety was very good. There was a mild installation site irritation, with the majority of patients having a very mild irritation, which was described as feeling menthol. That lasted for less than 1 minute in the majority of patients. There were no other significant adverse events, and only 1% of patients discontinued their medication in the reproxalap group.

So, in conclusion, this is the evaluation of a new drop, reproxalap, which is a RASP inhibitor. Primary endpoints of Schirmer testing and Schirmer responding were significant. The ocular discomfort and four symptom questionnaire dryness scores were significantly improved. The patients did have some mild irritation site, but only a few discontinued the medications. And what I was impressed about in this study was that for me, for a dry eye product to be relevant, it has to work quickly, it has to be efficacious, and it has to have low side effects. And in my opinion, reproxalap met all of these criteria for an effective drug for the management of dry eye.

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