Silk-derived protein-4 (SDP-4), a substance that mimics proteins found on the ocular surface, is a safe and effective multi-modal treatment for alleviating severe dry eye disease (DED) symptoms, according to a study published in the American Journal of Ophthalmology.1
DED is characterized by chronic inflammation on the ocular surface. This inflammation damages the surface by disrupting the mucin protein layer, which forms a protective tear film. Despite the importance of protein in the tear film, no commercially available eye drops incorporate the component as an ingredient.
About SDP-4-CS201
Trial Name: Study to Evaluate the Safety and Efficacy of SDP-4 in Subjects With Dry Eye Disease (DED) (SDP-4-CS201)
Clinicaltrials.gov Identifier: NCT03889886
Sponsor: Silk Technologies, Ltd.
Summary: SDP-4-CS201, is a Phase 2, multi-center, double-masked, randomized, vehicle-controlled, dose-response, parallel-group study designed to evaluate the ocular and systemic safety and efficacy of SDP-4 ophthalmic solution in subjects with moderate to severe dry eye disease over a 12-week treatment period.
Research has shown that more than 60% of patients discontinue using prescription eye drops within a year due to unsatisfactory results and unwanted side effects such as burning, stinging, redness, and dysgeusia.2 What’s more, artificial tears do not often suffice to treat severe symptoms. Recognizing the need for more effective treatments, investigators assessed the safety and efficacy of SDP-4, a naturally derived, anti-inflammatory wetting agent, compared to a vehicle control in patients with moderate to severe DED.
READ MORE: Survey: Dry Eye Is Common, But Americans Remain Uneducated About the Condition
The exploratory, first-in-human, phase 2 study evaluated the impact of baseline symptom severity on treatment efficacy outcomes in 2 distinct cohorts of patients with DED.
The first cohort participated in a dose-ranging study (0.1%, 1%, and 3% SDP-4) lasting 84 days. SDP-4-CS201 (NCT03889886) was conducted at 26 sites and included 296 participants. The second cohort participated in a single-dose study (1% SDP-4) lasting 56 days. SDP-4-CS202 (NCT04535947) was conducted at 5 sites and included 144 participants.
All study participants had a history of using artificial tears within 30 days prior to screening and agreed to discontinue use during the study. The eye with the shorter tear break-up time (TBUT) on day 1 of randomization was designated as participants’ study eye. The vehicle control consisted of the same eye drop formulation, but did not contain SDP-4.
About SDP-4-CS202
Trial Name: Study to Evaluate the Efficacy of SDP-4 in Subjects With Dry Eye Disease (DED) (SDP-4-CS202)
Clinicaltrials.gov Identifier: NCT04535947
Sponsor: Silk Technologies, Ltd.
Summary: SDP-4-CS202 is a Phase 2, multicenter, double-masked, randomized, vehicle-controlled, parallel group study designed to evaluate the ocular efficacy of SDP-4 ophthalmic solution in subjects with moderate to severe dry eye disease over an 8-week treatment period.
Participants were instructed to instill 1 drop of study medication into each eye twice daily for 84 days in the first cohort and 56 days in the second cohort. Investigators noted that the second cohort was limited to 56 days based on results from the first cohort that indicated this was a sufficient treatment period to assess eye drop efficacy.
Participants rated DED symptoms using a Visual Analog Scale (VAS) ranging from 0 (no discomfort) to 100 (maximal discomfort) as part of the Symptom Assessment iN Dry Eye (SANDE) questionnaire. This questionnaire assesses the combined frequency and severity of DED symptoms. TBUT was measured by applying fluorescein dye trips and timing in seconds how long it took for the tear film to break up.
The mean baseline total SANDE score for the first cohort ranged from 61 to 71 on the VAS, indicating moderate to severe DED. The score improved by day 7 in all treatment groups, with a mean reduction from baseline ranging from 7 to 10 points, and this improvement continued throughout the 84-day study, with a final mean reduction from baseline ranging from 25 to 30 points.
Throughout the study, and on day 84, the mean reduction in total SANDE score was highest for the 1% SDP-4 group, reaching a mean reduction of 30 points compared to 26 points for the vehicle group.
In the second cohort, the mean total SANDE score at baseline ranged from 56 to 57 on a 100-point VAS. Investigators noted that this was lower than the first cohort due to an adjustment in the SANDE questionnaire screening criteria for moderate patients. This measure improved starting on day 14 in both treatment groups and continued throughout the study.
On day 56, the mean reductions in the total SANDE score for the 1% SDP-4 and vehicle groups were 17 and 19 units, respectively.
When comparing the 2 cohorts receiving the 1% SDP-4 treatment, the first cohort, which had more severe symptoms, showed a statistically significant reduction in patient-reported symptoms on day 14 (95% CI: -13.2%, 6.4%; P = 0.005) and day 56 (95% CI: -23.6%, -1.0%; P = 0.042). By day 84, symptoms in the first cohort had improved by an average of 45.7% as measured by the total SANDE score. These results demonstrate that the 1% SDP-4 treatment effectively alleviated DED symptoms in the first cohort of patients who were more severely symptomatic.
In the first cohort, TBUT improved from approximately 3 seconds at baseline to an average of 2.2 seconds with 1% SDP-4 treatment by day 28, representing a 72% increase on average. By day 84, both groups normalized to a similar level.
In the second cohort, TBUT improved from 3.4 and 3.7 seconds at baseline to an average of 1.4 seconds with 1% SDP-4 by day 14, compared to 1.1 seconds with vehicle.
All treatments were safe and well tolerated, and there were no serious eye-related or other adverse events reported in patients using either SDP-4 or the vehicle control.
According to investigators, “the results of this study demonstrate that 1% SDP-4 eye drops offer [potential as a single product solution], providing both comfort at use and significant symptom reduction over time." Findings from this study could inform future clinical practices on the treatment of DED for the more than 400 million people worldwide with the condition.3
READ MORE: Eye Health Resource Center
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References
1. Lawrence BD, Karpecki PM, Infanger DW, Levy B. Silk-derived protein-4 versus vehicle control in treating patients with moderate to severe dry eye disease: a randomized clinical trial. Am J Ophthalmol. Published online August 30, 2024. doi:10.1016/j.ajo.2024.08.034
2. White DE, Zhao Y, Ogundele A, et al. Real-world treatment patterns of cyclosporine ophthalmic emulsion and lifitegrast ophthalmic solution among patients with dry eye. Clin Ophthalmol. 2019;13:2285-2292. doi:10.2147/OPTH.S226168
3. Dana R, Bradley JL, Guerin A, et al. Estimated prevalence and incidence of dry eye disease based on coding analysis of a large, all-age United States health care system. Am J Ophthalmol. 2019;202:47-54. doi:10.1016/j.ajo.2019.01.026
