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Phase 2 study initiated for oral anti-VEGF, anti-PDGF inhibitor
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MIAMI — An oral tyrosine kinase inhibitor under study for use in treating wet age-related macular degeneration has moved forward into a phase 2 trial, a speaker said.
Reporting positive phase 1 study results for X-82 (Xcovery Vision), an inhibitor of both anti-VEGF and anti-PDGF activity, Jason S. Slakter, MD, said at Angiogenesis, Exudation, and Degeneration 2015, “[X-82] has low toxicity in oral administration. Phase 1 study has shown some anatomic benefit, and a phase 2 program is kicking off.”
Jason S. Slakter
Preclinical studies demonstrated that oral administration of X-82 at doses of 50 mg or more were able to reach and exceed the concentrations needed to inhibit blood vessel activity in target tissue in the back of the eye, he said.
The phase 1 open-label, ascending repeat-dose study in exudative AMD looked at dose-limiting toxicity. Initial patients were heavily treated refractory cases. “These are people getting frequent regular anti-VEGF injections and yet still exhibiting exudation on their OCTs,” Slakter said.
Patients received daily or alternate-day oral X-82 at doses of 50 mg, 100 mg, 200 mg or 300 mg. The study did enroll some patients in the higher-dose regimens who were treatment-naïve, he said.
Follow-up every 4 weeks measured best corrected visual acuity and the need for Lucentis (ranibizumab, Genentech) rescue therapy as seen on SD-OCT. Twenty-eight of 35 patients completed the full 24-week therapy period, with the majority maintaining or improving visual acuity.
“Twenty-two of the 28 had been actively treated with anti-VEGF therapy with persistent exudation and yet when converted to this oral agent gained almost five letters of vision,” he said.
Regarding safety, three patients demonstrated elevation in transaminase levels, which returned to normal upon discontinuation of medications.
Phase 2, which kicked off this week, will investigate the potential of X-82 in patients who demonstrate the ability to achieve a dry macula in response to anti-VEGF therapy, that is, Eylea (aflibercept, Regeneron). The primary endpoint will be non-inferiority in visual acuity at 1 year. Secondary endpoints will include the number of aflibercept injections given and anatomical changes as seen on SD-OCT.
Disclosure: Slakter reports receiving research grant support from Acucela, Ampio, Bayer, Centocor, Genentech, Genzyme, GSK, Lpath, Novagali, Ohr, Oraya, Regeneron, Sanofi-Aventis, Santen, ThromboGenics and Xcovery Vision; consulting for Acucela, Lpath, Ohr, Oraya, Regeneron and Xcovery Vision; and stock ownership in SKS Ocular and Ohr Pharmaceutical.