Single Ascending Doses of DARPin®, MP0112, Show Potential for Quarterly Dosing in DME

Abstract

Purpose: : DARPins ® are a novel class of small, single domain proteins which can be selected to bind any given target with high affinity and specificity. MP0112 is a potent VEGF inhibitor with a long ocular half-life. Animal studies indicate that dosing frequency in patients may be reduced 3-4 fold compared with current standard therapy.This clinical study assessed the safety and preliminary efficacy of DARPin® MP0112 during 16 weeks in patients with DME.

Methods: : This is a Phase I/II, open-label, non-controlled, trial in the US. Eligible patients were aged >50 years with long-standing DME. Six patients were included per cohort in 3 ascending cohorts to receive a single dose of MP0112 via intravitreal injection. Safety and efficacy assessments over the 16-week period included adverse events, BCVA and OCT.

Results: : Eighteen subjects were enrolled at 4 participating sites in the US. The mean age was 65 years with 61% of patients being males. The majority of patients enrolled had received multiple prior treatments with Laser, Avastin, Kenolog and/or Lucentis for DME in the study eye.MP0112 was safe and well tolerated. The most frequent adverse event was a transient, sterile inflammation that resolved without visual consequences. Initial results from an interim analysis conducted for the first 15 patients completing the 16-week study time point have shown promising efficacy in spite of the majority of patients having long standing, refractive DME. Six of 15 patients (40%) showed an improvement of 10 or more letters in BCVA at Week 4, Week 12, and Week 16. In addition, 8 of 15 (53%) patients showed an improvement in OCT of greater than 50 microns at Week 4, and 4 of 15 (27%) patients at week 12 and 16.

Conclusions: : DARPin MP0112 represents a showcase for a novel class of therapeutic proteins in ophthalmology and a promising new long-acting anti-VEGF treatment option for patients with DME as well as other ocular neovascular conditions requiring chronic anti VEGF therapy.

Clinical Trial: : http://www.clinicaltrials.gov NCT01042678

Keywords: edema • diabetic retinopathy • retina