OPT-302 Improves Acuity in Combination with Aflibercept

David Boyer, MD

Opthea Ltd. has announced positive three-month data from its phase 1b therapy for diabetic macular edema patients who did not respond sufficiently to first-line anti-VEGF-A therapy. If the drug candidate continues to show positive results in further study, it has the potential to be a breakthrough for patients who currently have few treatment options.

The drug candidate, called OPT-302, is a soluble form of vascular endothelial growth factor receptor 3 (VEGFR-3), also referred to as a “trap” molecule. It works by blocking the activity of VEGF-C and VEGF-D, proteins that cause blood vessels to grow and leak and contribute to retinal diseases.

In this study, OPT-302 was administered in escalating doses of .3, 1.0, or 2.0 mg, in combination with 2.0 mg of aflibercept. The 9 patients in the study were given a total of 3 intravitreal injections. Each injection was spread out by 4 weeks. Each patient had a history of diabetes and persistent DME despite an average of 6.3 injections with an anti-VEGF-A therapy.

The patients’ eyes showed visual and anatomical improvement at 12 weeks, and the data showed results improved as the dosages escalated.

Principal investigator David Boyer, MD, clinical professor of ophthalmology at the University of Southern California Keck School of Medicine, said this category of patient is in need of additional treatment options.

“I am highly encouraged by the evidence of efficacy and continued favorable safety profile for OPT-302 combination therapy which has potential to benefit the many diabetic patients who have limited responses to anti-VEGF-A treatment,” he said, in a press release.

The company told MD Magazine® that patients who don’t respond to an anti-VEGF-A therapy can be offered corticosteroids. However, those corticosteroids have important limitations.

“Corticosteroids may address the underlying inflammatory process of DME, however corticosteroid treatment is associated with marked elevations in intraocular pressure and cataract formation which limits long-term use,” the company said. “Use of a combination therapy, such as OPT-302 in combination with a VEGF-A inhibitor may result in better efficacy and also delay or prevent the need to switch patients to corticosteroids.”

Laser photocoagulation is an option for some patients with non-center-involved edema, but the company said that laser therapy isn’t right for every patient because it can be risky and the benefits to visual acuity are limited.

DME affects about 2 million people around the world. Anti-VEGF-A therapies are the preferred initial treatment at the moment, but Opthea said 60-70% of patients who take those therapies don’t achieve visual acuity gains of more than 15 letters after 12 months. These patients could benefit from OPT-302, the company said.

However, Opthea says it plans to market the drug, if approved, as a first-line therapy, rather than simply a fallback.

In the meantime, the company is enrolling patients in a phase 2a study, in which the company will evaluate OPT-302 in combination with aflibercept versus aflibercept alone. The company also said this week it had completed enrollment for a phase 2b study of the drug. Results from both studies are expected in late 2019.