Article Date: 4/1/2014

When the Pipeline Runs “Dry”
DRY EYE DISEASE

  in development

When the Pipeline Runs “Dry”

Here’s a list of the emerging pipeline of dry eye treatments.

WILLIAM L. MILLER, O.D.. M.S., PH.D.
HOUSTON, TEXAS

ILLUSTRATION BY BOB KAYGANICH

The dry eye disease (DED) market is set to grow about $4 billion through the next decade, says a June 2013 article from GlobalData, a global research and consulting company for the healthcare industry. New avenues for delivery, as well as novel pharmaceuticals and vehicles that are currently under investigation, will present new treatment options to eyecare professionals. Here’s a look at the various DED treatments in the pipeline.

Cyclosporine 2.0

Restasis X, a higher concentration of cyclosporine 0.05% (Restasis, Allergan), the calcineurin inhibitor immunosuppressant that treats the inflammatory component of DED to increase the eye’s ability to produce tears, is set for a phase 2 U.S. clinical trial in patients with moderate to severe DED.

As of early April, the study is not yet open for participants.

LFA-1

Lifitegrast 5.0% ophthalmic solution, formerly SAR 1118 (Shire Pharmaceuticals) is a small-molecule integrin antagonist that decreases inflammation via inhibition of lymphocyte function-linked antigen 1 (LFA-1) and precluding its binding to intercellular adhesion molecule-1 (ICAM-1), impacting T-cell activation and cytokine (protein) release, says Shire Pharmaceuticals. The interaction between LFA-1 and ICAM-1 plays a significant role in DED-associated chronic inflammation.

Corneal fluorescein and conjunctival lissamine green staining were significantly decreased, and ocular discomfort and dryness improved upon Lifitegrast 5.0% use b.i.d. through 84 days, reveals results of a phase 3 U.S. clinical trial published in the February 2014 issue of Ophthalmology. The other main subjective measure, the vision-related OSDI, did not show improvement.

Currently, the small-molecule integrin antagonist is undergoing a Safety Study of Lifitegrast to Treat Dry Eye (SONATA) phase 3 U.S. study. Once Shire Pharmaceuticals has the results, which they expect within the next couple of months, they plan on talking with the FDA about the next steps, says Eric Rojas, Investor Relations for the pharmaceutical company.

Anakinra

Anakinra (Kineret, Sobi) is an IL-1 receptor antagonist that targets the IL-1/IL-1R1 signal pathway to increase tear secretion and normalize mucin. It is currently FDA-approved in injection form for moderate to severe rheumatoid arthritis patients who have failed to achieve relief with other drugs.

Topical Anakinra 2.5% significantly decreased DED symptoms and corneal epitheliopathy in patients who had DED linked with meibomian gland disease (MGD), shows the April 18, 2013 online edition of JAMA Ophthalmology.

Tacrolimus

Tacrolimus is a macrolide that inhibits calcium-dependent T-cell activation. It is currently FDA-approved in oral and injection form post-allogenic organ transplant to decrease immune system activity and, thus, reduce the likelihood of transplant rejection, and in topical form for eczema, especially atopic dermatitis.

Tacrolimus 0.03% ophthalmic solution improved tear stability and ocular surface status in Sjögren syndrome patients, says the August 2012 issue of Cornea.

MIM-D3

MIM-D3 ophthalmic solution (Mimetogen Pharmaceuticals) is a tyrosine kinase (TrkA) receptor agonist that prompts mucin production.

Twice-a-day dosing of MIM-D3 after 28 days, “demonstrated protection against the effects of a controlled adverse environment challenge on dry eye signs and reduced patient-reported diary symptoms, with a favorable safety profile,” says June 2013’s Journal of Clinical Ophthalmology.

A phase 3 clinical study is currently underway.

SI-614

SI-614 ophthalmic solution (Seikagaku) is a modified hyaluronate with a tear-stabilizing effect created by the company’s proprietary technology. Specifically, the modified hyaluronate stabilizes the lipid, aqueous and mucin layer of the tear film.

Thealoz

Trehalose 3% (Thealoz, Spectrum Thea Pharmaceuticals) is a disaccharide created by organisms, such as fungi. It is proposed to protect surface epithelial cells, particularly those exposed to dessication, says November 2012’s Current Eye Research. Thealoz eye drops are available in the United Kingdom.

The disaccharide is currently undergoing a phase 4 U.S. study for the treatment of DED.

Pulsed light therapy

The University of Miami is currently recruiting patients who have MGD and DED for a U.S. clinical trial to determine whether pulsed light therapy decreases DED symptoms and improves the clinical stigmata of DED associated with MGD in facial rosacea patients, which includes ocular rosacea.

Out of the U.S. pipeline

For those following the DED therapeutic pipeline, note that Diquas 3% ophthalmic solution (diquafosol sodium, Santen Pharmaceuticals), halted U.S. trials. Santen will target markets, such as Europe and Latin America, to release the drug, which is available in Japan.

Also, the development program for Rebamipide 2% ophthalmic suspension (Acucela and Otsuka Pharmaceutical) recently ceased in the U.S. due to trial outcomes that did not meet Otsuka’s expectations, said a company spokesperson. Under the name Mucosta, the drug has been available in Japan since 2012.

The changing landscape

To keep abreast of the ever-changing landscape of dry eye therapy, visit www.fda.gov/drugs, www.centerwatch.com/drug-information/fda-approvals and www.clinicaltrials.gov.

With the growing demand to treat DED in our practices, it is exciting to learn that several treatment modalities in the pipeline may find their way to daily use in this patient population. OM

Dr. Miller is an associate professor and chair of the Clinical Sciences Department at UHCO, an adjunct professor at Dublin Institute of Technology and editor of Contact Lens and Anterior Segment Update (CLASU.org). Send comments to optometricmanagement@gmail.com.



Optometric Management, Volume: 49 , Issue: April 2014, page(s): 29, 30, 32