A phase III study program investigating abicipar pegol (Allergan) for the treatment of neovascular age-related macular degeneration (nAMD) is underway based on promising efficacy and safety results in phase II studies.
“Abicipar pegol is the first-in-kind designed ankyrin repeating protein (DARPin) studied in the eye, and it is an exciting molecule,” said Pravin U. Dugel, MD. “Like ranibizumab (Lucentis, Genentech), abicipar pegol is an antagonist to all isoforms of VEGF-A, but the DARPin is smaller. (This) allows for good tissue penetration, and results of in vitro and animal studies show that it is a more potent inhibitor of VEGF-A, binds with greater affinity, and has a longer intravitreal half-life than ranibizumab.”
Dr. Dugel is managing partner, Retinal Consultants of Arizona, Phoenix, and clinical professor, USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles.
“Furthermore, in a multidose phase II study, abicipar pegol showed potential for treating nAMD with less frequent injections compared with ranibizumab.”
DARPins are recombinant proteins that are genetically engineered to bind to a specific target. Besides being small, potent, and having high specificity and binding affinity, DARPins are stable, which translates into good shelf-life, and highly soluble, which could allow for mixing with other agents and formulation in novel drug delivery systems.
The phase II study program for developing abicipar pegol as a treatment for nAMD was comprised of 3 stages. Most relevant to clinical practice, the third stage was a double-masked study that randomized 64 treatment-naïve patients to abicipar pegol 1 mg (n = 25), abicipar pegol 2 mg (n = 23), or ranibizumab 0.5 mg (n = 16).
Abicipar pegol was administered at weeks 0, 4 and 8, while ranibizumab was injected every 4 weeks through week 16. Patients were examined every 4 weeks through week 20.
The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline to week 16, and the analysis showed numerically greater improvement in the abicipar pegol 1 mg and 2 mg groups compared with the ranibizumab-treated controls (+6.3 letters and +8.2 letters versus +5.3 letters, respectively).