Ophthalmology · Clinical trials
Dry Eye Disease Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About dry eye disease — and why its trials are hard
Dry eye disease (DED) is a common, multifactorial disorder of the tear film and ocular surface, characterised by tear-film instability, hyperosmolarity, inflammation and neurosensory abnormalities. It causes grittiness, burning, fluctuating vision and reduced quality of life, and is broadly divided into aqueous-deficient and evaporative (often meibomian gland dysfunction) subtypes. Management begins with artificial tears, lid hygiene and environmental measures, escalating to pharmacotherapy targeting inflammation or tear dynamics. Approved prescription therapies include topical anti-inflammatory immunomodulators cyclosporine (Restasis) and lifitegrast (Xiidra, an LFA-1 antagonist), the cholinergic-agonist varenicline nasal spray (Tyrvaya) that stimulates natural tear production via the trigeminal pathway, and perfluorohexyloctane (Miebo), a semifluorinated alkane that reduces tear evaporation in evaporative DED. Clinical development is notoriously difficult because of high and variable placebo responses and poor correlation between signs and symptoms, so trials require dual sign and symptom endpoints, and many candidates have failed one co-primary. Common endpoints include corneal and conjunctival staining, Schirmer tear test and patient-reported dryness scores.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| cyclosporine ophthalmic emulsion 0.05% (Restasis) | 2003 | Dry eye disease (anti-inflammatory immunomodulator) | Phase 3 cyclosporine program | Increase in Schirmer tear production (categorised responders) | ~15% achieved ≥10 mm Schirmer improvement vs ~5% vehicle; increased tear production over 6 months |
| lifitegrast ophthalmic solution 5% (Xiidra) | 2016 | Dry eye disease (LFA-1 antagonist) | OPUS-1, OPUS-2, OPUS-3 | Inferior corneal staining (sign) and eye dryness score (symptom) | Consistently improved eye dryness score vs placebo; reduced inferior corneal staining in OPUS-1 |
| varenicline solution nasal spray 0.03 mg (Tyrvaya) | 2021 | Dry eye disease (nicotinic cholinergic agonist) | ONSET-1 and ONSET-2 | Proportion achieving ≥10 mm improvement in Schirmer score at week 4 | ONSET-2: ~47% reached ≥10 mm Schirmer improvement vs ~28% vehicle control |
| perfluorohexyloctane ophthalmic solution (Miebo) | 2023 | Dry eye disease (anti-evaporative, semifluorinated alkane) | GOBI and MOJAVE | Total corneal fluorescein staining (sign) and eye dryness VAS (symptom) | Significant reductions in total corneal staining and eye dryness score vs hypotonic saline control by day 57 |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in dry eye disease development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| diquafosol tetrasodium (P2Y2 agonist) — US phase 3 (INS365 / Prolacria program) | Failed to meet US co-primary corneal staining endpoints; not approved in the US (though approved in Japan and parts of Asia) | High placebo response and inconsistent sign endpoints across trials; regulatory bar for dual sign-and-symptom benefit not met |
| lifitegrast (initial pivotal sign endpoint) — OPUS-1 | Met the co-primary sign endpoint (inferior corneal staining) but missed the co-primary symptom endpoint (visual-related function), delaying approval | Sign-symptom dissociation and placebo response; approval only followed after OPUS-2/OPUS-3 demonstrated symptom benefit |
Choosing the right endpoint
Primary endpoints that matter in dry eye disease trials
- Corneal/conjunctival staining — Objective sign endpoint (fluorescein/lissamine) grading ocular surface damage; frequently a co-primary
- Schirmer tear test — Measures aqueous tear production; responder thresholds (e.g. ≥10 mm) used for Restasis and Tyrvaya
- Eye dryness score / symptom scales — Patient-reported symptom endpoints (VAS, OSDI); required as a co-primary given sign-symptom dissociation
- Tear-film break-up time / osmolarity — Markers of tear-film stability and hyperosmolarity supporting diagnosis and anti-evaporative mechanisms
How iNGENū runs dry eye disease trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Dry Eye Disease clinical trials — FAQs
Why do so many dry eye drugs fail in trials?
How does Miebo differ from anti-inflammatory drops?
What makes Tyrvaya's mechanism unusual?
Ready to discuss your dry eye disease trial?
Talk to our physician-led team about an FDA-ready, cost-efficient trial design.
Request a proposal