Lpath, Inc. (OTCBB: LPTN), the category leader in lipidomics-based therapeutics, reported positive summary results of its single-dose Phase 1 clinical trial of iSONEP™ in wet-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. Most of these positive effects appear to be largely independent of the effects seen when wet-AMD patients undergo treatment with Lucentis® or with off-label use of Avastin®, the predominant market leaders.
Due to the small sample size, all biological effects described above and below can only be characterized as correlative at this time; no causal relationship has yet been established, statistically or otherwise.
The most significant benefit observed was a regression in choroidal neovascularization (CNV), which is the underlying cause of the disease that eventually leads to degeneration of the macula, the area of the retina responsible for central vision. 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 typical, as the published data (Heier JS et al. Ophthalmology. 2006;113:642e1-642.e4) suggest that, 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, a potentially serious condition that is often a part of the pathology of wet AMD. 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. Neither Lucentis nor Avastin typically produce this type of clinical benefit with a single dose.
A key observation was that of the five patients that showed the strongest biological effect, all five had a component of occult-type CNV (either pure occult CNV or "minimally classic" CNV). Further, these five patients were the only ones in the Phase I study that were diagnosed with occult disease. In other words, all of the patients with a component of occult 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-à-vis those of Lucentis and Avastin is significant. Wet AMD is characterized by the pathologic disruption of the retina, which is caused collectively by (i) new-blood-vessel growth in the choroid layer under the retina, (ii) sub-retinal fibrosis, (iii) general inflammation in the retinal area, and (iv) edema caused by new blood vessels that do not form perfectly and are thereby permeable (or leaky).
Lucentis and Avastin target the protein VEGF, a validated 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.