OC-01 (Varenicline Solution) Nasal Spray for the Treatment of Dry Eye Disease Signs and Symptoms in Subjects with Autoimmune Disease: Integrated Data from ONSET-1 and ONSET-2

Abstract

Purpose

We evaluate the treatment effect of OC-01 (varenicline solution) nasal spray (VNS) in dry eye disease (DED) subjects from two randomized trials who self-reported autoimmune disease (AID).

Patients and Methods

Post hoc subgroup analysis of subjects reporting a history of AID from the integrated OC-01 VNS 0.03 or 0.06 mg and vehicle control (VC) treatment groups of the ONSET-1 and ONSET-2 trials. Mean change in Schirmer test with anesthesia score (STS, mm) and Eye Dryness Score (EDS) from baseline to 28 days was compared between OC-01 VNS and VC groups. Consistency of treatment effect in subjects with and without AID was evaluated using treatment–subgroup interaction terms in ANCOVA models for mean changes from baseline STS and EDS, and in a logistic regression model for proportion achieving ≥10 mm STS improvement.

Results

Of the 891 participants, 31 reported comorbid AID. In all models, the treatment–subgroup interaction terms were not significant (p>0.05), indicating consistency of therapeutic effect of OC-01 VNS in subjects with and without AID. In subjects with AID, the treatment difference for STS was 11.8 mm and −9.3 for EDS and difference for proportion of subjects with ≥10 mm STS improvement was 61.1%. The most common adverse event was sneeze (82–84%), graded as mild by 98% of subjects.

Conclusion

OC-01 VNS demonstrated consistency in improving both tear production and patient-reported symptoms in subjects with AID, consistent with pivotal ONSET-1 and 2 trial results. Further investigation is warranted, and results may further support use of OC-01 VNS for DED in AID patients.

Keywords:

• dry eye disease
• autoimmune disease
• Eye Dryness Score
• nicotinic acetylcholine receptor
• Schirmer test score
• varenicline nasal spray
• Tyrvaya

Abbreviations

ANCOVA, analysis of covariance; CI, confidence interval; EDS, eye dryness score; gAChR, ganglionic acetylcholine receptors; M2, M3, M4, muscarinic receptors 2, 3, 4; M3AChR, muscarinic acetylcholine receptor 3; P2X7, purinoreceptor 7SD, standard deviation; STS, Schirmer Test Score; VC, vehicle control; VNS, varenicline solution nasal spray.

Data Sharing Statement

The data used to support the primary findings of this study are available at ClinicalTrials.gov (NCT03636061 and NCT04036292).

Ethics Approval and Informed Consent

This study was conducted in accordance with the principles of Declaration of Helsinki and in compliance with the ICH E6 GCP Consolidated Guideline, ISO 14155:2011, and the applicable US FDA 21 CFR Regulations. Before clinical study initiation, the protocol and all amendments, the informed consent form, any other written information given to subjects, and any advertisements planned for subject recruitment was approved by an IRB/IEC (Alpha IRB, San Clemente, CA).

Acknowledgments

Medical writing assistance was provided by Tony Realini, MD, MPH of Hypotony L.L.C. and was funded by Oyster Point Pharma, Inc. Portions of these data were presented at the Association for Research in Vision and Ophthalmology Annual 2022 Meeting; May 1–5; Denver, Colorado, and Women in Ophthalmology 2022 Summer Symposium; August 25–28; Monterey, California.

Author Contributions

All authors made significant contributions to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

J.M.S. is an investigator and advisor for Oyster Point Pharma, Inc. She reports personal fees from Zeiss, Allergan, and Forsight V6; equities from Journey 1, Neurotrigger, and Novus Vision, outside the submitted work. M.M.G. is an advisor of Oyster Point Pharma, Inc. She reports that she has invested $300 in stocks of Kala; advisory board member for Claris Bio and Dompe. S.M. is a speaker, advisor and advisory board member for Oyster Point Pharma, Inc. She is also a speaker of and/or advisory board member for Allergan, Bausch & Lomb, Bruder, Cynosure, Dompe, Eyevance, Horizon, Lumenis, Ocuphire, RVL, Novartis, Science Based Health, Sun, and Tarsus, outside the submitted work. J.N. is an employee and shareholder of Oyster Point Pharma, Inc. He reports patents (9504644, 9504645, 9532944, 9597284, 10456396, and 11224598) issued to Oyster Point Pharma, Inc. M.M. is an employee and shareholder of Oyster Point Pharma, Inc. A.G. is an employee and shareholder of Oyster Point Pharma, Inc. G.B. is an employee and shareholder of Oyster Point Pharma, Inc. L.H.H. is an employee and shareholder of Oyster Point Pharma, Inc. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was sponsored by Oyster Point Pharma, Inc., manufacturer/licensee of OC-01 (varenicline solution) nasal spray.