Lancovutide (Moli1901) Dry Eye Studies

Lancovutide (Moli1901) Mechanism of Action

Development of Lancovutide (Moli1901) for Dry Eye Disease

Lancovutide, formerly known as "Moli1901," formulated as an ophthalmic solution, is being evaluated for the treatment of dry eye disease.  Lancovutide is a 19 amino acid polycyclic peptide produced from the fermentation of Streptomyces cinnamoneus. It promotes the hydration of epithelial tissue by opening an alternate salt channel. Lancovutide and other agents or hormones that stimulate secretion are commonly referred to as “secretagogues”. In dry eye disease, it is hypothesized that lancovutide administered via ocular instillation will hydrate the surface of the eye preventing irritation and possible ocular injury.

The molecular target of lancovutide is the phospholipid phosphatidylethanolamine (PE) present in the cellular membrane. Moli1901 binds to the polar head of PE and induces changes in intracellular calcium levels, which in turn activate calcium dependent chloride channels. These alternative calcium activated chloride channels produce an output of chloride and water. Patients with dry eye disease could theoretically experience increased hydration of the eyes from the instillation of lancovutide ophthalmic solution.

To maximize tolerability, solutions instilled into the eye should be neutral or slightly alkaline. To further maximize patient comfort, the pH of lancovutide ophtalmic solution is adjusted to approximately 7, similar to that of the natural tear film.

Initial clinical Phase 1 work in Europe in healthy volunteers and in the US in subjects with dry eye syndrome indicate that multiple doses and various regimens of the compound are safe.

The lancovutide ophthalmic solution program is currently in Phase 2 development in the US, where a multiple regimen study has been completed in select eye care study centers.  The data from that study, leading to the next development steps, are being evaluated.

A Scientific Advisory Board (SAB) has been chartered to provide expert input to the development of lancovutide for ophthalmic indications.  The SAB is Chaired by Roger Vogel, MD, Chief Medical Officer of Rx Development Resources, Inc. in Tampa, Fl.  Members include Gary Foulks, MD, FACS, Professor in the Department of Ophthalmology & Visual Sciences at the University of Louisville in Kentucky; Edward J. Holland, MD., Director of Cornea and External Disease at the Cincinnati Eye Institute and Professor of Clinical Ophthalmology at the University of Cincinnati in Ohio; and Andrew J.W. Huang, MD, MPH., Associate Professor and Director of Cornea & Refractive Surgery at the University of Minnesota Medical Center in Minneapolis, Minnesota.  

Dry eye is commonly treated with over-the-counter artificial tears (saline solution) as a purely palliative therapy to lubricate the eyes. Prescription products on the market and in development for dry eye disease in the US can be segmented into two categories: anti-inflammatory medicines focused on alleviating the inflammatory component of dry eye and secretagogues focused on stimulating tear secretion. Anti-inflammatory drugs are most applicable for the severe dry eye segment (10% of the dry eye patient population). Secretagogues, such as lancovutide, however, can potentially be used in all dry eye sufferers including those with only intermittent symptoms and can also be used in combination with anti-inflammatory therapies. Lancovutide has a unique mechanism of action within this product category by targeting a phospholipid in the cellular membrane and changing the permeability for calcium and chloride ions. This action facilitates hydration of the epithelium.