An Australian company is moving to clinical trials of a drug which, when combined with Lucentis or Eylea, could improve outcomes for people living with wet (neovascular) age related macular degeneration. OPT-302 is under development by Circadian Technologies, a small Australian biologics drug development company capitalised at AU$26 million, which holds extensive worldwide intellectual property patents in respect of VEGF-C, VEGF-D and VEGFR-3.
CEO Dr. Megan Baldwin said OPT-302, tested in preclinical models on mice, is similar in structure to Eylea and Lucentis and in its activity as a VEGF trap, yet novel because it targets VEGF-C and VEGF-D rather
“OPT-302 is a soluble receptor that blocks VEGF-C and VEGF-D and inhibits the hallmarks of wet AMD in preclinical models, including blood vessel growth and vessel leakage.
There is great opportunity to improve patient responses by targeting more than one factor involved in disease progression. Existing therapies, such as Lucentis and Eylea, target VEGF-A that promotes blood vessel growth and leakage through its receptor VEGFR-2. VEGF-C can also induce angiogenesis and vessel leakage through the same receptor. Combined inhibition of VEGF-A and VEGF-C has the potential to improve patient response by more effective inhibition of the pathways involved in disease progression.”
OPT-302 is a soluble receptor that blocks VEGF-C and VEGF-D and inhibits the hallmarks of wet AMD in preclinical models
Positive Preclinical Data
Dr. Baldwin said the activity of OPT-302 to resolve wet AMD lesions in mice was comparable to the activity of Eylea in the same model, and when the two drugs were used together, the treatments were even more effective.
The preclinical data with OPT-302 in combination with Eylea appears to be comparable to the activity of Fovista when used in combination with a VEGF-A inhibitor in the same animal model. Fovista, developed by Ophthotech Corp, has completed phase two trials to test safety and efficacy when used in conjunction with Lucentis. The trials showed that patients dosed with both Fovista and Lucentis saw their vision improve by a mean of 10.6 letters on a standard eye chart, compared to 6.5 letters for patients only taking Lucentis. Fovista exhibited a favourable safety profile and no significant safety imbalances were observed for Fovista combination therapy as compared to Lucentis monotherapy.
Based on these results, Ophthotech Corp has initiated a phase three clinical program to evaluate the safety and efficacy of Fovista in combination with anti-VEGF-A drugs (Lucentis, Eylea, Avastin) compared to anti-VEGF-A monotherapy for the treatment of newly diagnosed patients with wet AMD.
Dr. Baldwin said combined, OPT-302, Fovista and Lucentis or Eylea, would act as an inhibitor of all three VEGF pathways. “If Fovista makes it to market, there is potential for us to conduct a clinical trial with Fovista and assuming success, co-formulation with one or more existing therapies would be the way to go.”
Circadian Technologies has established a clinical advisory board to provide insight into the regulatory and clinical development strategy for OPT-302. The four-person board has extensive experience in development of novel and FDA approved therapeutics for wet AMD including Macugen, Fovista, Eylea and Lucentis. The board comprises Prof. Pravin Dugel from Retinal Consultants Arizona and Keck School of Medicine USC, Prof. Peter Campochiaro from John Hopkins Wilmer Eye Institute, Prof. Kameran Lashkari from Schepens Eye Research Institute, Harvard Medical School and Prof. Mark Gillies from Sydney’s Save Sight Institute.
Speaking of the potential for OPT-302 to save sight for people with macular disease, Prof. Gillies said, “Lucentis and Eylea represent a generational breakthrough in the treatment of neovascular AMD, but some patients may respond sub optimally. Lucentis blocks VEGF-A, Eylea blocks VEGF A, -B and PlGF. These molecules are ligands for VEGF receptors 1 and 2. As a decoy receptor for VEGF-C and -D, OPT-302 may augment VEGF blockade by inhibiting activation of VEGFR-2 and -3.”
Circadian aims to commence a phase one clinical trial at multiple sites in the United States during the second quarter of 2015 to demonstrate the safety and efficacy of OPT-302.