Ocuphire Pharma reported topline efficacy and safety results from its phase 2 ZETA-1 (NCT04692688) trial assessing oral APX3330, its investigative drug candidate, for diabetic retinopathy (DR) treatment.
Tell me about APX3330.
APX3330 is a twice-daily oral tablet drug candidate that targets the apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) protein, referred to as Ref-1. Blocking Ref-1 leads to a decrease in proangiogenic and proinflammatory transcription factors found in retinal and choroidal vascular diseases. (via)
Talk about the study.
The randomized, double-masked, placebo-controlled phase 2 trial enrolled 103 patients with at least one eye that met the criteria for moderately severe to severe non-proliferative DR (NPDR) or mild proliferative DR (MPDR) and was conducted at 25 sites in the U.S.
Each patient’s study eye had a baseline Early Treatment Diabetic Retinopathy Study (ETDRS) diabetic retinopathy severity scale (DRSS) step of 5, 6, or 7.
Patients randomly received either 600 mg of APX3330 or a daily placebo for 24 weeks. (via)
What were the endpoints?
Each endpoint assessed +/- 1, 2, 3, and 4-step improvement and worsening in patients’ DRSS at weeks 12 and 24; changes in best-corrected visual acuity and central subfield thickness; and safety and tolerability.
Results?
APX3330 failed to meet its primary endpoint (% of patients with a ≥ 2-step improvement in DRSS at week 24 in the study eye).
However, for the prespecified secondary endpoint, APX3330 achieved a statistically significant reduction in disease progression at 24 weeks.
None of the APX3330-treated patients exhibited a binocular ≥ 3-step worsening of DRSS from baseline compared with 16% for placebo-treated patients (P= 0.04).
Investigators also reported stable visual acuity, a majority of mild treat-related adverse events (AEs), and no serious treatment-related AEs. (via)
Anything else?
Further efficacy endpoints supported APX3330’s ability to slow DR progression and preserve vision.
Take home.
Ocuphire expects the phase 2 trial’s secondary endpoint to be the primary endpoint in a planned phase 3 trial, which will be confirmed at a meeting with the FDA at the end of the phase 2 trial.