Alternative therapies in development for DME

Issue: February 2014

KOLOA, Hawaii — A number of treatment regimens in development may prove superior to current standards of care for center-involved diabetic macular edema, according to a speaker here.

Multiple pathways are being explored to enhance treatment of diabetic macular edema, whether alone or in combination with anti-VEGF for treatment of DME. Agents include PF-655, AKB-9778 and iCo-007, Quan D. Nguyen, MD, MSc, said at Retina 2014.

PF-655 is a synthetic chemically modified siRNA that targets the RTP801 gene, which is expressed in human age-related macular degeneration.

Quan D. Nguyen

In one stratum of the phase 2b MATISSE study – a prospective randomized double-masked dose-ranging study – 240 subjects are currently being enrolled to evaluate the efficacy and safety of PF-655 alone and in combination with ranibizumab, Nguyen said.

“The distribution of the PF-655 following intravitreal injection indicates that it has a very high concentration in the retina, and therefore we are able to control the process,” Nguyen said.

Another novel agent is the AKB-9778, which activates the Tie2 pathway, the key control axis for retinal vascular stability, Nguyen said. In a phase 1b/2a study intended to determine safety, tolerability and biological activity of the agent in patients with DME involving the center of the fovea with central subfield mean thickness of 325 microns or greater, all doses were well tolerated, there were no injection site reactions, there were no effects on hematologic or liver function tests and hemodynamic effects were transient.

In the phase 2 IDEAL trial study, iC-007 inhibits C-raf expression and blocks MAP kinase signaling. The trial is intended to assess safety of repeated iCo-007 injections in patients with DME as monotherapy and in combination therapy. –by Patricia Nale

Disclosure: Nguyen has received consulting fees from Bausch + Lomb and Santen; he has done contracted research for Genentech, Regeneron and Santen.