ThromboGenics NV (OTC:TBGNF) recently announced that it received a 3 million euro grant from the Flemish agency for Innovation by Science and Technology to support development of new therapeutics for diabetic macular edema. The new program will complement Thrombogenics's newly launched product, Jetrea, for Vitreomacular Adhesion, a progressive eye disease that can lead to blindness affecting about 500,000 patients per year in the U.S. and Europe. It will take years for Thrombogenics' DME program to mature from a preclinical stage to commercial launch, but it's a solid strategy supporting the company's existing assets in eye disease.
Now, with an established revenue stream from Jetrea, which is marketed by Novartis' (NYSE:NVS) Alcon unit outside the U.S., Thrombogenics is seeking to expand its product portfolio into a larger and potentially richer indication, diabetic macular edema (DME). Alcon paid Thrombogenics 90 million euros (or about $124 million) in milestone payments following the European approval and launch of Jetrea.
Lucentis leads the DME market
About 21 million people worldwide are estimated to have DME. In 2013, Thrombogenics had about 7,000 patients treated with Jetrea, for about $27.9 million in sales.
Lucentis, originally developed by Genentech, which was subsequently acquired by Roche (OTC:RHHBY) , is the leading therapy for DME, with 1.689 billion Swiss francs, or about $1.9 billion in 2013 sales. The drug is a member of the class of VEGF inhibitors and was previously approved for age-related macular degeneration and macular edema following retinal vein occlusion.
Lucentis was the first major new treatment for DME in 25 years. In clinical trials, a 0.5 mg dose improved vision in patients with the disorder as measured by a gain of 15 letters, or three lines on a standard eye chart from baseline after 24 months of treatment, in 42.5 percent of patients.
The biggest competitor for Lucentis is another Roche product, Avastin, which is approved for colon cancer, non-small cell lung cancer, kidney cancer, and glioblastoma. Because it is also a VEGF inhibitor, the success of Lucentis in eye disease indications suggest that it, too, could perhaps be effective in those diseases.
The connection between cancer and eye disease may seem random at first, but VEGF inhibitors are designed to prevent the growth of new blood vessels. And it turns out that webs of tiny new blood vessels contribute to eye disease as well as the growth of cancerous tumors. Off-label Avastin has been used as an alternative to the pricier Lucentis, and some studies have supported its use in diabetic macular edema. Regeneron's Eylea is another VEGF inhibitor with off-label application to DME.
Room for improvement
There's room for competition, however, both in terms of efficacy (more lines of vision for more patients) and route of administration. Lucentis and off-label Avastin are administered as injections into the eye, so an oral or topical treatment would have an instant advantage.
Thrombogenics says that it will use the IWT grant funding to study the role of a new pathway in DME that is thought to contribute to the disease by regulating vascular leakage and inflammation.
The company has not signaled whether it will seek to study Jetrea in DME for potential label expansion, but that is an idea that has been floated in the medical literature. Jetrea is a form of the naturally occurring molecule, plasmin, which has a role in blood coagulation. Its activity in VMA is attributed to breaking down laminin and fibronectin, proteins believed to cause adhesion of vitreous to the retina.
Jetrea's potential in DME may lie in mimicking the effects of a common surgical option, removal of the vitreous gel from the eye. Since fibronectin and laminin are components of the vitreoretinal interface, targeting those proteins could replicate the benefit of the vitrectomy without the surgical complications. However, no clinical studies have yet been launched, and it's important to remember that ThromboGenics has only one approved drug -- something to consider in your investing thesis.