Sun Pharmaceutical Industries Limited released phase 4 clinical results on Cequa (cyclosporine ophthalmic solution) 0.09% indicated to treat the signs and symptoms of dry eye disease (DED).
Refresh me on Cequa.
Approved for topical ophthalmic use by the FDA in 1983, the cyclosporine molecule is a calcineurin inhibitor immunosuppressant indicated to increase tear production in patients with keratoconjunctivitis sicca (dry eye). Subsequently, Cequa was approved by the FDA in August 2018.
From Cequa’s prescribing info, the preservative-free eye drop’s recommended dosage is one dose twice daily (approximately 12 hours apart) into each affected eye.
The single-use vial should be discarded immediately after use.
What makes it unique?
The eye drop is currently the first and only chronic dry eye treatment to be formulated using Sun Pharma’s proprietary nanomicellar NCELL Technology delivery system—designed to surround cyclosporine (as the drop’s active ingredient) and deliver it directly to the surface of the eye for treatment.
In essence, this technology can potentially improve Cequa’s ocular surface penetration.
Gotcha. So what previous clinical data shown?
A multicentered, randomized, double-masked, vehicle-controlled phase 3 confirmatory study of dry eye patients reported clinically and statistically significant improvements in tear production and ocular surface integrity among Cequa-treated patients.
And before that, a phase 2b/3 trial also demonstrated clinically and statistically significant increases in tear production after 84 days, as well as well-tolerance.
Any adverse reactions reported?
Across both studies, the most common were:
- Instillation site pain after administration (22%)
- Conjunctival hyperemia (6%)
Others (in 1%-5% of patients) included:
- Eye irritation
- Blepharitis
- Urinary tract infection
- Headache
- Bronchitis
Gotcha … now how about this new trial?
Per the company, the 12-week, multicenter, phase 4 study examined 124 patients (mean age of 65.5 years; 88% female) with “inadequately controlled” DED (diagnosed at least 3 months prior) who were on current Restatisis (cyclosporine ophthalmic emulsion) 0.05% therapy for a minimum of 3 months.
All patients proceeded to receive the recommended prescription dosage of Cequa for the study duration.
What was measured?
- Corneal fluorescein staining (CFS)*
- Scored on 0-4 grading scale using 0.5-point increments
- Modified Symptom Assessment in Dry Eye (mSANDE)
- 0-100 scale for dryness and irritation (frequency and severity)
- Total scored with sum of all five corneal area zones
Each test score was measured at baseline and Weeks 4, 8, and 12 (or upon early discontinuation from the study).
*The investigators assessed CFS in all five zones of the cornea, allowing for an enhanced characterization of corneal health. Of note, dry eye trials tend to only assess a few corneal areas.
And the findings?
Overall, Cequa was generally well tolerated, exhibiting a safety profile consistent with previous clinical data.
Among the patients in the modified intent-to-treat (mITT) population, the following was observed:
- CFS
- Mean total at baseline = 5.7 (3.37 for standard deviation [SD])
- Week 4 = 4.0 (3.12)
- Week 8 = 2.9 (2.54)
- Week 12 = 2.7 (2.3)
- mSANDE
- Baseline = 67.1 (21.05)
- Week 4 = 48.4 (23.31)
- Week 8 = 44.2 (24.28)
- Week 12 = 38.3 (25.99)
Any adverse reactions?
Less than half (43.3%) of patients reported at least one treatment-emergent adverse event (TEAE), with the majority as mild (73.8%).
Most common among these were installation site irritation and pain; other treatment-related AEs occurred in less than 2% of patients.
What was different about this trial vs previous ones?
According to Sun Pharma’s Head of Medical Affairs, Ophthalmics Brittany Mitchell, OD, the study, “is notable for its design, which allows for use of artificial tears, thus replacing real-world conditions as closely as possible for a controlled clinical trial.”
Gotcha. So what’s next?
Dr. Mitchell noted that this data is the first of a new series of assessments from the phase 4 trial which will continue to report on Cequa’s efficacy for treating this patient population.
This data was released during the American Academy of Optometry (AAOPT) annual meeting in New Orleans, Louisiana, October 11-14, 2023.