Published in Ocular Surface

Tyrvaya® (varenicline solution) Nasal Spray 0.03 mg: A Different Path to Treating the Signs and Symptoms of Dry Eye Disease

Eyes On Eyecare Client Team

Eyes On Eyecare Client Team

This post is sponsored by Oyster Point Pharma, Inc.
2 min read
Learn how to treat dry eye disease using a nasal spray. Real-time animations will help you explore if it's a good fit for your practice and your patients.
Tyrvaya® (varenicline solution) Nasal Spray 0.03 mg: A Different Path to Treating the Signs and Symptoms of Dry Eye Disease

Dry eye disease is a chronic, multifactorial disease that can be
characterized by tear film
instability and deficiency or loss of tear film homeostasis3

According to the Tear Film and Ocular Surface Society Dry Eye Workshop (TFOS DEWS II), in healthy tear film, the production and composition of the tear film are tightly regulated, resulting in a stable and protected ocular surface (tear film homeostasis).1,2 The International Panel of Experts in Dry Eye Disease emphasizes the importance of tear film instability as a “key criterion” for a readily measured clinical definition of dry eye disease.3

Tear film instability and deficiency leads to dry eye disease3

An imbalance of the components of the tear film, increased tear film evaporation, and decreased tear production can all contribute to tear film instability and may result in dry eye disease.4 This causes the cornea to become vulnerable, perpetuating the harmful cycle of dry eye disease in many patients.

There is no substitute for a patient’s own
natural tear film5

A healthy and stable tear film plays an important role in eye health. It nourishes, hydrates, and protects the ocular surface.6  Instability and deficiency in healthy tear film is the unifying element of dry eye disease,3 while increasing the production of your patients’ own natural tear film may restore stability.3,6
Natural tears are complex and dynamic, containing more than 2,000 molecules8-11 including:
  • Anti-inflammatories10,1
  • Lipids8
  • Antibodies12
  • Growth factors 10,2
  • Antimicrobial proteins and peptides10,12
  • Mucins10
  • Electrolytes and metabolites10
Artificial tears may provide temporary relief and may contain synthetic agents and preservatives6,7 such as:
  • Hypromellose6
  • Propylene glycol6
  • Benzalkonium chloride6
  • Potassium chrloride6
  • Sodium borate6

Overview of the pathway of tear film production

External or internal stimuli activate the trigeminal nerve in the nasal cavity to send signals to the brain. Those signals are interpreted by the brain and sent back via the parasympathetic pathway to the lacrimal function unit (LFU).14,15
Three components of the LFU are the lacrimal glands, the meibomian glands, and goblet cells. This is how the trigeminal parasympathetic pathway plays a role in maintaining tear film homeostasis.

Tyrvaya® (varenicline solution) nasal spray harnesses the body's natural tear film to treat dry eye disease16

Increased production of natural tear film can reduce the signs and symptoms of dry eye disease.17

While the exact mechanism of action is unknown at this time,  Tyrvaya® is believed to activate the trigeminal parasympathetic pathway via the nose, resulting in an increase in natural tear film production. In fact, innervation of the lacrimal glands, meibomian glands, and goblet cells occurs when breathing through the nasal passage, activating the trigeminal parasympathetic pathway and resulting in the production of one third of a patients’ basal tears.18

Studies enrolled 1000+ patients with mild, moderate, or severe dry eye16,11,19, 20, 21, 22

Tyrvaya® was evaluated in three randomized, vehicle-controlled, double-masked studies in which adults aged >22 years diagnosed with dry eye disease received 1 spray of either active drug or vehicle in each nostril twice daily. Patient population was 75% female with a mean age of 59 years.16,11,19-22
The Schirmer test is used to evaluate natural tear production. Sterile paper strips are applied to the eye between the palpebral conjunctiva of the lower eyelid and the bulbar conjunctiva. The eyes are closed for 5 minutes, the paper is removed, and the amount of moisture is measured. The score is measured from 0-35 millimeters.16 In the Tyrvaya® clinical trials, tear film production was measured by anesthetized Schirmer’s scores.
ONSET-1 (N=182)19 *
The primary endpoint in this study was the mean change in Schirmer’s Test Score (STS) from baseline at Week 4.
ONSET-2 (N=758)20,22 *
The primary endpoint in this study was the percentage of patients who had a > 10 mm improvement in STS from baseline at Week 4.
MYSTIC (N=123)11 *
This study evaluated the mean change from baseline in STS at Week 12.

These studies were designed with real-world use in mind:

  • Enrollment was not limited by baseline Eye Dryness Score (EDS) (range, 2-100)
  • Use of artificial tears was allowed in both the Tyrvaya® and vehicle groups
  • Studies did not include a placebo run-in period
*ONSET-1: Tyrvaya® 0.03 mg (n=48); varenicline solution 0.006 mg (n=47); varenicline solution 0.06 mg (n=44); vehicle (n=43). Note: the 0.006 mg dose was only used in ONSET-1.

ONSET-2: Tyrvaya® 0.03 mg (n=260); varenicline solution 0.06 mg (n=246); vehicle (n=252).

MYSTIC: Tyrvaya® 0.03 mg (n=41)16,11;varenicline solution 0.06 mg (n=41); vehicle (n=41).16,11

The approved dosage of Tyrvaya® is 0.03 mg.


Natural tear film production increased by > 10 mm in ~50% of patients16, 19, 20

Tyrvaya® demonstrated a mean change in Schirmer’s Test Score (STS) by at least 10 mm from baseline at Week 4.21,22,23** Natural tear film production increased by > 10 mm in ~50% of patients. Specifically, in the ONSET-1 Study, 52% of patients (n=48) experienced an increase in tear film production at Week 4 while in the ONSET-2 Study, 47% of patients (n=260) also experienced an increase in tear film production by Week 4.

Onset of action was measured as early as ~ 5 minutes following first dose20, 21

On Day 1 in each trial, a baseline anesthetized Schirmer’s test was performed. Tyrvaya® was then administered and a Schirmer's test was performed. Schirmer’s test results were measured at ~5 minutes.
An increase in tear film production was observed as early as approximately 5 minutes after the first dose, though it was not a prespecified endpoint.21-23

Tyrvaya® increased natural tear production over 12 weeks

The Tyrvaya® group met the primary endpoint at 12 weeks, which showed a statistically significant mean increase of 10.8 mm from a baseline of about 5 mm in Schirmer’s Test Score, compared to the vehicle group with a 6 mm increase. Although Weeks 1, 4, and 8 were not prespecified endpoints, the Tyrvaya® group had a 10 to 11 mm increase in Schirmer’s Test Score across all timepoints, as compared to the vehicle group with a 6 mm to 7 mm increase.
All subjects were Hispanic or Latino. Tyrvaya® group mean baseline STS 5.5 mm (n=41); vehicle group mean baseline STS 5.3 mm (n=41).11 All randomized and treated patients were included in the analysis and missing data were imputed using last-available data.11
Limitations: Ex-US, single-center study. Weeks 1, 4, and 8 were not prespecified endpoints.11

Tyrvaya® was well-tolerated in clinical studies

Important Safety Information

The most common adverse reaction reported in 82% of patients was sneezing.16 In patients who reported sneezing, 98% of them rated it as mild (281/287).22 In ONSET-2, 65% of sneezing resolved within 1 minute (159/244).22 No patients discontinued Tyrvaya® due to sneezing.21-23
Other common adverse reactions that were reported in > 5% of patients include:16, 21-23
  • 16% cough (55/349)
  • 13% throat irritation (44/349)
  • 8% instillation-site (nose) irritation (27/349)
Discontinuation due to all adverse events across all studies:21-23
2.0% Tyrvaya®-treated patients (7/349)
2.1% Vehicle-treated patients (7/335)

Indication

Tyrvaya®(varenicline solution) nasal spray is indicated for the treatment of the signs and symptoms of dry eye disease.
Please see full Prescribing Information.

Tyrvaya® is a twice-a-day nasal spray

Tyrvaya® is administered as 1 spray in each nostril, 2 times a day, ~12 hours apart. Before initial use of Tyrvaya®, patients need to prime the bottle 7 times and re-prime if not used for more than 5 days. If a patient misses a dose, they should resume regular dosing at their next scheduled dosing time (Do not take an extra dose to make up for a missed dose).
Tyrvaya® is an ocular surface-sparing treatment. The route of administration avoids applying medication to an already irritated ocular surface. Tyrvaya® is a preservative-free alternative to drops and it allows patients to keep contacts in during administration at the discretion of the eyecare professional. Patients with contact lenses were excluded from the clinical trials. Additionally, the route of administration limits disruption to eye makeup.

The Tyrvaya® way to spray

Please review the full Instructions for Use with your patients before they use Tyrvaya®.
Share these tips with your patients:
  • DO NOT spray into your sinuses.
    • Insert the tip of the nasal spray just past the nasal opening.  Aim the tip towards your ear on the same side of the nostril you’re spraying into.
  • DO Ensure proper tongue placement.
    • Press your tongue to the roof of your mouth
  • DO NOT inhale deeply.
    • Breathe gently as you press and release the applicator, just misting the inside of your nostril.  The medication will absorb into the wall of the nose where the nerve is located
  • DO NOT press the tip of the nasal applicator against the wall of the inside of the nose.
    • Leave a space between the tip of the nasal applicator and the wall of the inside of your nose.

How to Prescribe Tyrvaya®

Tyrvaya® 0.03 mg 8.4 mL —
Instill 1 spray in each nostril
BID for 30 days

From savings to support, we’ve got your patients covered. Learn more.

© 2022 Oyster Point Pharma, Inc. Tyrvaya®, and the Tyrvaya logo are the trademarks of Oyster Point Pharma, Inc. in the United States and certain jurisdictions. All rights reserved. All other trademarks are the rights of their respective owners. OP-TYR-001866 10/22

Important Safety Information
The most common adverse reaction reported in 82% of patients was sneezing. Events that were reported in 5-16% of patients were cough, throat irritation, and instillation-site (nose) irritation.
Indication
Tyrvaya® (varenicline solution) nasal spray is indicated for the treatment of the signs and symptoms of dry eye disease.
Please click here for full Prescribing Information.
1. Bron AJ, de Paiva CS, Chauhan SK, et al. Ocul Surf. 2017;15(3):438-510.
2. Craig JP, Downie LE. Tears and Contact Lenses. In: Phillips AJ, Speedwell L, eds. Contact Lenses. 6th ed. Elsevier; 2019:97-116.
3. Tsubota K, Pflugfelder SC, Liu Z, et al. Int J Mol Sci. 2020;21(23):9271.
4. Dartt DA, Willcox MD. Complexity of the tear film: importance in homeostasis and dysfunction during disease. Exp Eye Res. 2013;117:1-3.
5. Vicario-de-la-Torre M, Caballo-González M, Morales-Fernández L, et al. Polymers (Basel). 2018;10(4):1-13.
6. Jones L, Downie LE, Korb D, et al. Ocul Surf. 2017;15(3):575-628.
7. Rouen PA, White ML. Home Health Now. 2018;36(2):74-83.
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9. Dart DA, Willcox MDP. Exp Eye Res. 2013;117:1-3.
10. Willcox MDP, Argüeso P, Georgiev GA, et al. Ocul Surf. 2017;15(3):366-403.
11. Quiroz-Mercado H, Hernandez-Quintela E, Chiu KH, Henry E, Nau JA. Ocul Surf. 2022;24:15-21.
12. McDermott AM. Exp Eye Res. 2013;117:53-61.
13. Klenkler B, Sheardown H, Jones L, et al. Ocul Surf. 2007;5(3):228-239.
14. Dieckmann G, Fregni F, Hamrah P. Neurostimulation in dry eye disease-past, present, and future. Ocul Surf. 2019;17(1):20-27.
15. Pflugfelder SC, Cao A, Galor A, Nichols KK, Cohen NA, Dalton M. Nicotinic acetylcholine receptor stimulation: A new approach for stimulating tear secretion in dry eye disease. 2022;25:58-64.
16. Tyrvaya. Prescribing Information. Oyster Point Pharma; 2021.
17. Nelson JD, Shimazaki J, Benitez-del-Castillo JM, et al. Invest Ophthalmol Vis Sci. 2011;52(4):1930-1937.
18. Patel J, Levin A, Patel BC. Epiphora. 2022 Aug 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 32491381.
19. Wirta D, Torkildsen GL, Boehmer B, et al. Cornea. 2021;00(0):1-10.
20. Wirta D, Vollmer P, Paauw J, et al. Ophthalmology. 2021:6420(21):1-9.
21. Oyster Point Pharma. Data on file. OPP-002 (ONSET-1) Clinical Study Report. August 4, 2019.
22. Oyster Point Pharma. Data on file. OPP-101 (ONSET-2) Interim Clinical Study Report. October 13, 2020.
23. Oyster Point Pharma. Data on file. OPP-004 (MYSTIC) Clinical Study Report. March 19, 2020.
24. Aaron M, Solley WA, Broocker G. General Eye Examination. In: Palay DA, Krachmer JH, eds. Primary Care Ophthalmology. 2nd ed. Mosby; 2005:1-23.
25. Akpek EK, Amescua G, Farid M, et al. Ophthalmology. 2019;126(1):P286-334.


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Led by our Director of Client Services Dr. Antonio Chirumbolo, OD, the Eyes On Eyecare Client Team leverages innovative content solutions and data-backed insights to create memorable educational content that resonates with eyecare providers worldwide.

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Important Safety Information: The most common adverse reaction reported in 82% of patients was sneezing. Events that were reported in 5-16% of patients were cough, throat irritation, and instillation-site (nose) irritation.

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