Dry Eye Dx and Tx
The Wait Is Almost Over
BY WILLIAM TOWNSEND, OD, FAAO
On Oct. 10, 2003, the U.S. Food and Drug Administration (FDA) approved Restasis (cyclosporine emulsion 0.05%, Allergan); 13 years later, U.S. eyecare providers and patients await approval of additional prescription medications for dry eye disease (DED). Fortunately, numerous viable candidates are currently in some stage of the FDA approval process. We will address a few of them in this article.
In March 2015, Ikervis (0.1% cyclosporine, Santen) received approval in the European Union for “treatment of severe keratitis in adult patients with dry eye disease, which has not improved despite treatment with tear substitutes.” Ikervis is instilled once per day, half the recommended frequency of Restasis. This may be possible because the drug is suspended in a cationic (positively charged) nanomolecular carrier that binds to anionic epithelial cell membrane (The Ophthalmologist, 2015), resulting in a four-fold tissue concentration of the drug. Novagali Pharma, which was recently acquired by Santen, completed two phase 3 FDA clinical trials using a similar, if not identical, product with positive results.
Novaliq is a German pharmaceutical company that uses unique drug delivery platforms to transform poorly soluble drugs into effective therapeutics. CyclASol is cyclosporine A 0.05% in a preservative-free solution of semifluorinated alkanes (SFAs). The company states that compounds dissolved in SFAs are believed to penetrate physiological barriers more easily than water-based preparations do; SFAs allow successful administration of drugs that might otherwise not reach therapeutic target levels. Novaliq is enrolling subjects in FDA phase 2 clinical trials that will evaluate the safety, efficacy and tolerability of CyclASol for the treatment of moderate-to-severe DED.
Lifitegrast (Shire, plc.) is an integrin; integrins facilitate the binding of leukocytes via intercellular adhesion molecules (ICAMs). Lifitegrast exerts its therapeutic effects by blocking the actions of ICAM-1. In the OPUS-1 study group, the authors reported reduced corneal (fluorescein) and conjunctival (lissamine green) staining and improved symptoms of ocular discomfort and eye dryness compared with placebo. There was no significant improvement in subjective dry eye or ocular discomfort. The OPUS-2 trial used a similar protocol, but the results differed in that lifitegrast did not improve inferior corneal staining, but significantly improved subjective dry eye symptoms.
Sosne et al (2015) reported the results of a small, phase 2 clinical trial using RGN-259 (thymosin β4 [T β4], RegeneRx) eye drops versus placebo to treat subjects who have severe dry eye. At the end of the treatment period, both groups showed improvement, but more so in the treatment group. At 56 days (28 days after the last treatment) the RGN-259–treated group had a 35.1% reduction in ocular discomfort and 59.1% reduction of total corneal fluorescein staining compared with the vehicle control. Tear film breakup time and increased tear volume production were also noted in the treatment group.
T β4 is a naturally occurring protein peptide found in most tissues and cells, but the highest concentrations are in lymphoid tissues, blood platelets, neutrophils, and macrophages. It exerts wound healing and anti-inflammatory properties and is believed to be important in corneal epithelial repair. Another FDA trial demonstrated the benefits of T β4 in treating individuals who have non-healing ulcers secondary to neurotrophic keratitis. CLS
For references, please visit www.clspectrum.com/references and click on document #248.
Dr. Townsend practices in Canyon, Texas, and is an adjunct professor at the University of Houston College of Optometry. He is president of the Ocular Surface Society of Optometry and conducts research in ocular surface disease, lens care solutions, and medications. He is also a consultant or advisor to Alcon, Allergan, NovaBay, TearScience, TearLab, and Science Based Health. Contact him at email@example.com.