Lpath, Inc., the industry leader in lipidomics-based antibody therapeutics, has initiated dosing in its Nexus clinical trial, in which iSONEP is being investigated as a treatment for wet AMD (age-related macular degeneration). Lpath entered into an agreement with Pfizer in 2010 that provides Pfizer an exclusive option for a worldwide license to develop and commercialize iSONEP.

In this phase II double-blind, multi-site trial, Lpath plans to dose 160 subjects that have not responded completely to a VEGF inhibitor (Lucentis or Avastin). These subjects will be randomized into four arms: VEGF inhibitor alone; combination of a VEGF inhibitor and iSONEP (lower dose); combination of a VEGF inhibitor and iSONEP (higher dose); and iSONEP alone.

Endpoints that will be studied include change in visual acuity, change in retinal thickness, and change in lesion size.

In Lpath's phase I trial, where subjects with wet AMD received only one injection, iSONEP met its primary endpoint of being well tolerated in all 15 patients. It also succeeded in meeting a key secondary endpoint in that a positive biological effect -- with a single dose -- was observed in most patients, almost all of whom had failed to respond to Lucentis and/or Avastin treatment.

One such benefit seen in the iSONEP phase I trial was a significant reduction (30%+) in the size of the choroidal neovascular lesion itself (i.e., excluding the fluid that has leaked from the lesion) in many of the subjects, all of whom were not responding well to treatment with the VEGF inhibitors at the time they were enrolled in the study. Significant reduction in lesion size with a single injection is not typical of VEGF inhibition.

One of these subjects experienced a 100% reduction in lesion size as of Day 45, as well as a complete flattening of his RPE detachment. This subject did not have to be re-injected with the "standard of care" (Lucentis or Avastin) for the entire twelve-month monitoring period following the iSONEP injection.

Another subject, who had undergone 16 prior treatments of Lucentis and Avastin without much response, was administered the highest dose of iSONEP studied (1.8 mg.). This subject not only experienced a 100% reduction in lesion size by Day 15, but also experienced a complete elimination of retinal swelling. The subject also did not have to be re-injected with Lucentis or Avastin for the entire 12-month monitoring period following the iSONEP treatment. These extended times to re-treatment suggest that any benefit derived from iSONEP may be durable, a particularly important attribute in this market.

Lpath hypothesizes that such distinctive benefits are due to powerful anti-angiogenic, anti-inflammatory, and anti-fibrotic mechanisms of action of iSONEP, which binds to and neutralizes the bioactive lipid, sphingosine-1-phosphate, or S1P. In various animal models of disease, iSONEP was shown to substantially reduce inflammation and angiogenesis in the eye (Campochiaro et al., Journal of Cellular Physiology, October 2008) and significantly mitigate ocular fibrosis (Grant et al., Experimental Eye Research, August 2008).

Glenn Stoller, MD, head of Lpath's ocular division, commented: “Although the VEGF inhibitors have raised the bar considerably in the treatment of wet AMD, there is significant room for improvement. These drugs treat retinal edema and vascular leakage, but they do little to eliminate or even reduce the lesion themselves, resulting in treatments that must be administered monthly or bi-monthly for life. We are hopeful that the reduction of lesion size that we saw in the iSONEP phase I trial will be repeated in larger groups of patients in trials such as Nexus.”

Scott Pancoast, Lpath's president and chief executive officer, added: “The Nexus study will help us determine whether iSONEP is efficacious enough to be used as a solo agent or if combination treatment is required. In addition, even though the Nexus study investigates those that have not responded completely to Lucentis/Avastin, we are hopeful that the results are convincing enough to extend the scope of subjects to treatment-naive patients in subsequent studies. In any case, the market potential for a drug that can provide additive benefits in wet AMD is substantial.”

Lucentis and Avastin are registered trademarks of Roche.