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  • Tyrogenex, JAMA Ophthalmology

    A novel oral tyrosine kinase inhibitor has the potential to reduce or even eliminate injection burden associated with wet-AMD, according to findings published online in JAMA Ophthalmology.

    However, the phase 1 trial had an unusually high dropout rate (29%), which may be a cause for concern.

    X-82 is a dual VEGF and platelet-derived growth factor (PDGF) inhibitor that is structurally similar to sunitinib, but designed to limit tissue accumulation to minimize adverse effects. The tablets are also being investigated for pancreatic neuroendocrine tumors and renal cell carcinoma.

    Conducted at 5 U.S. retinal clinics, this open-label, uncontrolled, dose-escalation study enrolled 35 participants with wet AMD. Over a period of 24 weeks, subjects received oral X-82 at 50 mg on alternate days (n=3), 50 mg daily (8), 100 mg on alternate days (4), 100 mg daily (10), 200 mg daily (7), or 300 mg daily (3), along with intravitreal anti-VEGF therapy on a PRN basis using predefined retreatment criteria. Participants underwent best-corrected visual acuity measurement, fundus examination, and spectral-domain OCT every four weeks. 

    Of the 25 participants (71%) who completed the 24 weeks of X-82 treatment, 15 required no anti-VEGF injections and all except 1 maintained or improved their visual acuity.

    Mean central subfield thickness reduced by 50 μm, with 8 participants (all of which received at least 100 mg daily) demonstrating sustained reductions despite no anti-VEGF injections.

    Ten participants withdrew consent or discontinued prematurely, 6 owing to adverse events which included diarrhea (n=6), nausea (5), fatigue (5) and transaminase elevation (4).

    “Whilst this is primarily a safety study, these results strongly suggest X-82 has biological activity, as the frequency of intravitreal anti-VEGF injections was far lower than expected,” according to lead author Timothy L. Jackson, PhD, FRCOphth, consultant ophthalmic surgeon at King’s College Hospital. “Subject to confirmatory studies, the possibility of a pill to treat wet AMD is undoubtedly exciting, as the current treatment with repeated eye injections imposes a substantial burden on patients and health care providers.”

    Manufacturer Tyrogenex recently completed enrollment of 157 patients in a phase 2, randomized, double-masked, placebo-controlled trial of X-82 for wet AMD in January 2017. That study is expected to complete in January 2018.