Lpath, Inc., the industry leader in lipidomics-based antibody therapeutics, has initiated dosing in its PEDigree clinical trial where iSONEP is being investigated as a treatment for retinal pigment epithelium detachment ("RPE detachment" or "PED"). 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 human proof-of-concept trial, Lpath plans to dose 32 subjects -- 16 at a lower dose and 16 at a higher dose -- that have PED secondary to wet age-related macular degeneration (wet AMD) or polypoidal choroidal vasculopathy (PCV).
PED is a potentially serious condition that is often part of the pathology of wet AMD and PCV, yet no drug has yet been approved to treat PED. Even though patients with PED were excluded from the Lucentis pivotal trials, this drug is often used to treat such patients, but with incomplete success. As such, the prognosis for those suffering from PED continues to be poor.
Subjects in the PEDigree trial will receive up to three monthly intravitreal injections of iSONEP. The primary safety endpoint is the tolerability of consecutive monthly injections, and the primary efficacy endpoint is the percentage of subjects that experience complete flattening of their PED.
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 of the distinct benefits in phase I was the resolution (complete flattening) of PEDs in two out of the two subjects that presented with PED. One of these patients received no further treatment with the "standard of care" (Lucentis or Avastin) during the entire 12-month monitoring period following the iSONEP injection. The other was not re-treated until day 105. These extended times to re-treatment suggest that any benefit derived from iSONEP is durable, a particularly important attribute in this market.
Lpath hypothesizes that such distinctive benefits are due to iSONEP's powerful anti-inflammatory and anti-fibrotic mechanisms of action. In various animal models of disease, iSONEP was shown to substantially reduce inflammation 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).
The potential market for a drug that fully resolves PED is significant: it is estimated more than 500,000 people currently have PED, and with reasonable assumptions, the attainable market size is estimated to be more than $1.0 billion globally. These figures are expected to grow significantly as the "baby boomers" fill up the ranks of the 65+ age group.
Lpath plans to soon begin another iSONEP trial, a double-blind, 160-subject human-proof-of-concept trial to study the efficacy and safety of iSONEP in the broader wet-AMD patient population.
Glenn Stoller, MD, head of Lpath's ocular division, commented: “iSONEP is a first-in-class drug that has distinguished itself with promising animal data and, more recently, human data. A growing independent body of literature suggests that iSONEP's distinctive anti-inflammatory, anti-angiogenic and anti-fibrotic mechanisms could prevent both the early and the late stages of retinal damage, including the damage that often results when a PED fails to flatten over time.”
Scott Pancoast, Lpath's president and chief executive officer, added: “Because anti-VEGF agents like Lucentis and Avastin have demonstrated lackluster results in the treatment of PED patients, there is a significant unmet medical need. Both subjects presenting with PED in our phase I trial experienced a complete flattening of the PED. While that is a very small population, we are hopeful that we will see similar results in larger groups of patients as we continue our clinical development programme.”
Lucentis and Avastin are registered trademarks of Roche.
Lpath, a therapeutic antibody company, is the category leader in lipidomics-based antibody therapeutics, an emerging field of medicine that targets bioactive signalling lipids for treating a wide range of human disease.