Indirect Comparison Finds Nasal Spray Offers Improvements for Dry Eye

Patients with dry eye disease may experience a potentially greater earlier improvement in tear production and symptoms when treated with Oyster Point’s Tyrvaya (varenicline solution) nasal spray compared with Novartis’ eye drop Xiidra (lifitegrast), according to an analysis published in the Journal of Managed Care + Specialty Pharmacy. Dry eye disease is a common condition, causing discomfort for about 16.4 million Americans.

Darrell E. White, M.D.

Investigators, led by Darrell E. White, M.D., founder of SkyVision Centers in Westlake, Ohio, used matching-adjusted indirect comparison (MAIC), which is a form of population-adjusted indirect treatment comparisons (ITC). In these analyses, matched patient-level data from the clinical trials of one treatment are compared with aggregate data reported for trials of a separate therapy. This is an approach that is used when there are no head-to-head trial outcomes and allows for cross-study comparison.

“Comparative efficacy is ideally evaluated in head-to-head randomized trials, but in their absence, physicians, patients, payers, and formulary regulators rely on available evidence in selecting therapy and making policy decisions,” investigators wrote.

In this analysis, which was funded by Oyster Point Pharma, individual patient data from the phase 3 registrational trial of Tyrvaya 0.03 mg nasal spray (also referred to as OC-01) and aggregate data available from two phase 3 trials of Xiidra 5% ophthalmic solution. Tyrvaya is a highly selective cholinergic agonist that was approved by the FDA in October 2021. Novartis’ Xiidra was approved by the FDA in July 2016. Xiidra is a lymphocyte function-associated antigen 1 (LFA-1) antagonist.

Investigators analyzed data from 511 patients in the Tyrvaya phase 3 trial, 260 of whom were treated with Tyrvaya and 251 who were treated with vehicle control. They also analyzed data from two phase 3 trials of Xiidra. These included 588 patients in the OPUS-1 trial (293 treated with Xiidra and 295 with the comparator, in this case topical ophthalmic solution) and 718 in the OPUS-2 trial (358 treat with Xiidra and 360 treated with vehicle.

In this MAIC analysis, Tyrvaya produced greater improvement in mean Schirmer’s test score, a test used to determine whether the eye produces enough tears to keep it moist, and comparable or greater improvement in the Eye Dryness Score, a patient reported assessment.

One limitation of this analysis, investigators said, is that MAIC can only evaluate outcomes quantified similarly between studies; it cannot adjust for differences in time points assessed across studies. Investigators said they best matched disparate time points of evaluation by comparing the two-week time points and the four-week Tyrvaya time point to the six-week Xiidra time point to minimize bias.