Macular Degeneration

iSONEP: Positive phase-1 clinical trial results for ISONEP in AMD


Oct 26, 2009

Positive phase-1 clinical trial results for ISONEP in AMD

Lpath, Inc. reported positive results of its single-dose Phase 1 clinical trial of iSONEP, an anti-sphingosine-1-phosphate monoclonal antibody, in neovascular age-related macular degeneration (AMD) patients.

iSONEP met its primary endpoint of being well tolerated in all 15 patients at dose-levels ranging from 0.2 mg. to 1.8 mg. per intravitreal injection (three patients per dose level). No drug-related serious adverse events were reported in any of the patients.

iSONEP also succeeded in meeting a key secondary endpoint in that a positive biological effect was observed in an encouraging number of patients.

iSONEP is the ocular formulation of a monoclonal antibody that targets sphingosine-1-phosphate (S1P), a bioactive lipid that is dysregulated in cancer and other disorders of inappropriate angiogenesis and inflammation. S1P promotes angiogenesis, inflammation, cell survival, and cell proliferation, all of which have been implicated in AMD.

The most significant benefit observed was a regression in choroidal neovascularization (CNV). Of the seven patients that had a baseline lesion that was considered "large," four experienced a reduction exceeding 5 mm2 and three experienced a reduction of greater than 75% -- all with a single dose of iSONEP. This type of clinical benefit is not seen with anti-VEGF therapy. Even with repeated Lucentis dosing, the total physical size of CNV lesion does not show much reduction.

Another distinctive benefit was the resolution of retinal pigmented epithelium (RPE) detachment. Of two patients that were diagnosed with RPE detachment in the Phase 1 trial, both experienced complete or near-complete resolution of the condition -- again, with only a single dose of iSONEP.

A key observation was that all of the patients with occult-type CNV exhibited a strong positive biological effect during the 30-45 days following a single injection of iSONEP. This correlation has significant implications for Lpath's Phase II study design.

The fact that these biological effects are non-overlapping vis-a-vis those of Lucentis and Avastin is significant. Lucentis and Avastin target the protein VEGF, a promoter of permeable and leaky blood vessels, and appear to exert most of their beneficial effect via an anti-permeability action that results in resolution of intra and sub-retinal edema. However, the actual CNV lesion does not typically regress.

In contrast, iSONEP has been shown in various animal models of disease not only to reduce blood-vessel growth and leakiness, but to significantly mitigate ocular fibrosis and to substantially reduce inflammation in the eye. As such, iSONEP has the potential to be an effective wet-AMD treatment that may offer significant advantages over exclusively anti-VEGF approaches. It may also act synergistically with them as a combination therapy to address the complex processes and multiple steps that ultimately lead to vision loss for wet AMD patients.

Scott Pancoast, Lpath's president and chief executive officer, said: "We are very encouraged by the results of our Phase 1 trial with iSONEP, as the drug was extremely well-tolerated and showed the type of biological activity that we were hoping to see. We now have strong justification for further investigation of iSONEP's efficacy in one or more Phase 2 clinical trials."

WHAT IT MEANS TO YOU: It is very exciting to see these new drugs progress through the clinical trial process. While it may be several years before iSONEP becomes clinically available, it is clear that we will soon have new, and potentially better, treatment options for wet AMD.