Findings from the CEQUA’s Onset of Action Trial (COAT) study reported earlier this year offered investigators a look at the speed of onset of Sun Pharma’s CEQUA (cyclosporine ophthalmic solution) 0.09% in improving the ocular surface among patients diagnosed with dry eye disease (DED).
The results are just the latest phase 4 data supporting the FDA-approved formulation for chronic dry eye.
First up: this ophthalmic solution.
Developed under Sun Pharma, the preservative-free eye drop was FDA approved in August 2018; however, cyclosporine was first approved for topical ophthalmic use in 1983.
The science of it: Also referred to as cyclosporine A (CsA), cyclosporine is a calcineurin inhibitor immunosuppressant that interferes with T-cell function in the eye by blocking their activation and proliferation to reduce inflammation within the ocular surface.
- About the CEQUA formulation: This encompasses Sun Pharma’s proprietary nanomicellar NCELL Technology delivery system (read up on this here).
And the recommended dosing?
Per its prescribing information (PI), one dose should be instilled twice daily (BID; an estimated 12 hours apart) into the affected eye(s).
- To note: It can be used concomitantly with artificial tears—though 15-minute intervals are advised between products
Its efficacy: Results can be seen as early as 2 weeks and last as long as 3 months.
Now let’s talk clinical data.
CEQUA has already undergone extensive clinical investigation in various trials—as we’ve previously reported—including in comparison to Allergan, Inc.’s Restasis (cyclosporine ophthalmic emulsion) 0.05%.
To date, positive findings have indicated:
- Significant improvements from baseline in corneal fluorescein staining (CFS) seen as early as Week 4 and continuing to Week 12
- Significant improvements in best-corrected visual acuity (BCVA) at 12 weeks
- Most patients report their eyes feeling less dryness and irritation after 4 weeks of CEQUA use versus Restasis
- 69% of patients prefer CEQUA over Restasis by the end of 12 weeks
Nice! Next up: this new research.
The COAT was a multicenter, prospective, open-label, self-controlled, single-group study (NCT06482177) that evaluated CEQUA for improving certain measures (see below) in dry eye patients as early as 1 week after starting treatment.
- CFS
- Tear breakup time (TBUT)
- BCVA
- Standardized Patient Evaluation of Eye Dryness (SPEED) scores
- Conjunctival redness (on the Schulze scale)
Get into specifics on these participants and the setup.
A total of 46 patients (aged 47-91; 89% female) were enrolled and analyzed.
- All participants met the inclusion criteria, including signs of central or inferior CFS defined by the Oxford Scale Reduced TBUT ≤ 10 seconds.
- 26 patients’ left eye (57%) was analyzed
- 20 patients’ right eye (43%) was analyzed
The setup: Both eyes received CEQUA treatment BID (regardless of which eye was analyzed) and evaluated at four timepoints over a 28-day period.
- Baseline, Day 7, Day 14, and Day 28
What was measured?
The primary outcome included changes in corneal higher-order aberrations (HOA) after each of the four timepoints during treatment.
The secondary outcome included corneal staining, and the other outcome involved changes in BCVA—all measured at the same timepoints.
And the findings on Day 28?
Starting with HOAs: Significant improvements were observed in association with CEQUA treatment from baseline to Days 7 and 28 (p < 0.005 and p < 0.0001, N-1 Chi Squared Test, respectively).
These improvements were statistically significant at Days 7 and 28 for the majority of patients:
- Day 7 vs baseline: -57% (better) vs 26% (worse)
- Day 14 vs baseline: -35% (better) vs 57% (worse)
- Day 28 vs baseline: -59% (better) vs 35% (worse)
As an aside: Investigators noted that the totals may not equal 100% because patients whose HOAs changed by less than 0.01µ were considered unchanged.
Did they have anything to say about this fluctuation?
In their discussion, the study authors referred to previous research with other formulations of cyclosporine that have shown the drug’s best efficacy “occurring more than 30 days after initiation.”
Their input: “Clinicians should consider the possibility that full rehabilitation of the ocular surface may not occur as soon as 7 days.”
Any other comments to add about HOAs?
Just one. Keep in mind: Total corneal HOAs of ≤ 0.5µ was noted as a frequent measure of candidacy for multifocal implants.
- In this study: While only 7% of patients met these criteria at baseline, 48% of patients had HOAs of ≤ 0.5µ by Day 28.
What that suggests: “CEQUA is an appropriate medication choice for optimizing the ocular surface in preparation for a multifocal implant,” the authors stated.
Noted. So how did corneal staining fare?
That secondary outcome was eliminated in the following percentage of patients on their respective days:
- 28% by Day 7
- 37% by Day 14
- 61% by Day 28
And that other outcome of BCVA?
By Day 28, BCVA demonstrated what was referred to as a “significant” trend toward improvement.
Baselines versus (paired t-test using logMAR BCVA):
- Day 7: p < 0.075
- Day 14: p < 0.13
- Day 28: p < 0.043
What else to report on?
Significant improvements were noted for:
- SPEED scores by Day 7 (and through the 28 days)
- TBUT at each time point versus baseline
- Conjunctival redness compared to baseline
And as for tolerability: Just one patient withdrew from the study due to an intolerance to CEQUA.
Any notable limitations?
A few were called out, such as:
- Outcome measures may have been subjective (SPEED scores) or potentially prone to unmasked observer bias (corneal staining, TBUT)
- Despite this, objective measures (HOAs and BCVA) demonstrated “highly statistically significant improvements” with treatment that “paralleled the more observer-depending findings”
- Compliance of the self-administered education was difficult to ensure
- No vehicle control group was included
- A larger sample size may have achieved significance at all timepoints (instead of at most)
And for the future?
Additional research might include studies with larger sub-populations to evaluate the response to cyclosporine in the following patient demographics:
- Younger vs older patients (for context: this study featured older patients)
- Diagnosed with meibomian gland dysfunction (MGD) versus deficient DED
- Those of different races/ethnicities/genders
Lastly: What did investigators conclude?
Based on these latest results, CEQUA may be an appropriate drug to rapidly rehabilitate the ocular surface in DED patients preparing for refractive-cataract surgery.