Abicipar pegol (Allergan/Molecular Partners) met its primary and key secondary endpoints and demonstrated an acceptable overall safety profile in a phase II trial investigating use of the novel anti-VEGF-A agent for treatment of diabetic macular edema (DME).
“The phase II study data support progression of the research to phase III,” said Tarek S. Hassan, MD, professor of ophthalmology, Oakland University William Beaumont School of Medicine, Royal Oak, MI.
Abicipar pegol is a designed ankyrin repeat protein (DARPin), a new class of potential therapeutic agents for intraocular diseases.
“DARPins have some obvious advantages,” said Dr. Hassan. “These proteins are created fairly easily with recombinant techniques and are able to be created with a fairly high degree of specificity and affinity for their therapeutic targets. In addition, these proteins are very small and soluble, which allows the delivery of high amounts of the agent in a low volume, and they have the potential for long action.”
Abicipar pegol has a molecular weight of 34 kDa, which is much smaller than the molecular weight of the anti-VEGF antibodies and antibody fragments, and it is a highly potent blocker of the VEGF-A isoform.”
Phase II study details
Known as PALM, the phase II study was a prospective, multicenter, double-masked, controlled trial assessing the safety, efficacy, systemic pharmacokinetics, and immunogenicity of abicipar in patients with decreased vision due to centrally involved DME.
Eligible patients had ETDRS best corrected visual acuity (BCVA) ranging from ≥ 24 to ≤ 75 letters (Snellen equivalent 20/32 to 20/320) and central retinal thickness (CRT) > 300 µm or > 320 µm, depending on the optical coherence tomography (OCT) device used for measurement.
A total of 151 patients were randomized into four groups (1:2:2:2) to receive ranibizumab 0.5 mg (Lucentis, Genentech) every 4 weeks or abicipar 1 mg every 8 weeks (Q8W), 2 mg Q8W, or 2 mg Q12W. All four treatment regimens were initiated with monthly injections administered at Weeks 0, 4, and 8.
Findings from the primary endpoint analysis that assessed mean change in ETDRS BCVA from baseline to week 28 showed a gain of 9.6 letters in the ranibizumab arm and improvements of 4.9, 7.1, and 7.2 letters in the abicipar 1mg Q8W, 2 mg Q8W, and 2 mg Q12W groups.
“Clearly, abicipar seemed to be underdosed with the 1 mg Q8W regimen,” Dr. Hassan said.
In a secondary endpoint analysis evaluating the proportion of patients achieving BCVA of 70 letters or better (20/40 Snellen equivalent) at various follow-up visits, the outcome was as good as or better in all abicipar groups compared to the ranibizumab group except at week 20.
Mean change from baseline CRT was also analyzed as a secondary endpoint and was decreased significantly in all treatment groups. The largest decrease was achieved in the abicipar 1 mg Q8W group (-176.4 µm), while the changes were similar in the ranibizumab and the two abicipar 2 mg groups (range -158.8 µm to -162 µm).