OPT-302 Meets Phase 1/2A Endpoints as Pan-VEGF Inhibitor for nAMD

AUGUST 14, 2017
Thomas Castles
Opthea’s OPT-302 has received a favorable outlook for the treatment of neovascular Age-Related Macular Degeneration (nAMD), according to Pravin Dugel, MD (pictured), lead author of a phase 1/2A study that monitored the drug’s safety profile and potential to produce a positive biological signal.

OPT-302 represents a potential shift in the modern approach to treating nAMD, Dugel said, because current treatments primarily inhibit vascular endothelial growth factor (VEGF) A, but not VEGF C and VEGF D.

“There are robust preclinical studies to show that pan-VEGF inhibition – in other words, the inhibition of A, C and D – is more effective than the inhibition of VEGF A alone,” Dugel said at the 2017 annual meeting of the American Society of Retina Specialists in Boston. “OPT-302 is a trapped molecule that binds and neutralizes the activity of VEGF C and VEGF D, locking and binding receptors VEGFR2 and VEGFR3, as a potent inhibitor of both VEGF C, as well as VEGF D.”

The drug is being developed as a combination therapy with current treatments and could eventually allow for true pan-VEGF inhibition, he said.

A total of 51 patients were recruited for the study. 18 patients were recruited who were treatment-naïve and placed in a combination arm with OPT-302 plus ranibizumab (Lucentis/Genentech). 20 patients were recruited who were prior-treated patients in the same combination arm. The remaining patients were treated in a monotherapy arm, although Dugel emphasized that the drug is being tested for future use as a combination therapy.

“In the monotherapy arm, there was an improvement of 5.6 letters of vision. This occurred in both treatment-naïve patients as well as prior-treated patients,” Dugel said. “In the combination therapy arm and the treatment-naïve patient population, there was a mean improvement of 10.8 letters of vision. In the prior-treated patients – despite the severity of these patients – there was an improvement of 4.9 letters of vision.”

Approximately 33% of patients with notable improvements had gained 15 or more letters of vision by the end of the 12-week study. Further, there was a progressive decrease in the size of patients’ choroidal neovascular membrane.

“We also looked at patients who had eradicated neovascular membranes. In 50% of treatment-naïve patients, there was no detectable neovascular membrane after 12 weeks, as read by an independent waiting center,” Dugel said.

Moreover, the inhibition of VEGF C/D by intravitreal injections of OPT-302 in doses up to 2mg either as monotherapy or combined with suppression of VEGF-A with ranibizumab was safe and well tolerated. There were no treatment-related serious adverse events.

“This is a phase 1/2A study, and in any phase 1/2A study there are 2 goals – the first is for safety and another is for biological signal, and I think we’ve achieved both,” Dugel said.

In response to a question about his choice to use ranibizumab as combination therapy with OPT-302 instead of aflibercept (Eyelea/Regeneron), Dugel said it was important not to block VEGF B.

“You may not want to block VEGF B because there’s evidence that VEGF B is a neuroprotectant, so that might actually be a disadvantage. With pan-VEGF inhibition, you’re going to block A, C and D, but not B,” he said, adding that a larger study is currently being designed for the choroidal neovascular membrane using a control as well.
 

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