There remains a major unmet medical need for more effective dry eye treatments, and several companies have innovative new options in their pipeline. Current options have limited efficacy.
Originally believed to be primarily a disease of postmenopausal women with or without autoimmune disorders, it is now recognized that dry eye disease (DED) affects patients of both sexes at younger ages.
A chronic inflammatory disease, DED is the most common eye disease. It can have a significant impact on the quality of life of a sufferer. There remains a major unmet medical need for more effective treatments, as currently available treatments for DED have limited efficacy (particularly over the long-term), provide only symptomatic improvement and or are associated with safety and tolerability issues, such as burning or stinging, on instillation that limit their use.
Artificial tears generates close to $540 million in annual sales globally,1 and the U.S. spends more than $2 billion yearly on pharmaceuticals to treat DED.2
Patients with Sjögren’s syndrome dry eye spend 78% more on western medicine than those without the autoimmune disorder DED.3 There continues to be an unmet need for more effective treatments for DED, as is evidenced from the multitude of clinical studies listed in Clinicaltrials.gov that are under way or not yet recruiting.
Here is an overview of studies nearing completion and products that have been filed for regulatory approval.
On the horizon
Kala Pharmaceuticals has submitted a new drug application to the FDA for KPI-121 (0.25%) for the treatment of dry eye based on the strength of one phase II trial and two phase III trials, STRIDE 1 and STRIDE 2.
The trials enrolled almost 2,000 patients, and indicated statistical significance for the primary endpoint of conjunctival hyperemia, as well as the primary symptom endpoint of ocular discomfort severity.
If approved, KPI-121 would be first product indicated for the temporary relief of the signs and symptoms of DED and flares. The agent uses Kala’s AMPPLIFY drug delivery technology to better penetrate the target tissues.
In August, the company received a complete response letter (CRL) from the FDA regarding its new drug application (NDA) for KPI-121.
The STRIDE 3 trial is a multicenter, randomized, double-blind, placebo-controlled, parallel-arm study, comparing KPI-121 0.25% to vehicle (placebo), each dosed four times a day (QID) for two weeks in approximately 900 patients with DED.
Subjects who meet initial screening and inclusion/exclusion criteria undergo a two-week run-in period with vehicle. Subjects who continue to meet inclusion/exclusion criteria after the run-in are randomly assigned to receive either KPI-121 0.25% or vehicle for two weeks.
Data from the phase III clinical trial, STRIDE 3 (ClinicalTrials.gov Identifier: NCT03616899), is expected to be released by the end of the year.
In the pipeline
Aldeyra Therapeutics is now enrolling patients into the RENEW phase III clinical trial, which will evaluate the efficacy of reproxalap ophthalmic solution (0.25%) versus vehicle in 400 patients with moderate and severe DED.
Co-primary endpoints are ocular dryness and fluorescein nasal region ocular staining (ClinicalTrials.gov Identifier: NCT03879863). The phase III trial comes on the heels of successful phase IIb trial results, which demonstrated statistical superiority of reproxalap versus vehicle across multiple dry eye signs and symptoms.
1. Moshirfar M, Pierson K, Hanamaikai K, et al. Artificial tears potpourri: a literature review. Clin Ophthalmol. 2014;8:1419-33.
2. Hawkes N. US’s $2bn annual spend on dry eye disease “brings tears to your eyes,” say critics. BMJ. 2018;360:k492.
3. Yao W, Le Q. Social-economic analysis of patients with Sjogren’s syndrome dry eye in East China: a cross-sectional study. BMC Ophthalmol. 2018;18(1):23.