STUDY SUBJECTS

Major inclusion criteria:

• ≧ 50 years old
• Treatment naive neovascular AMD (nAMD)
• Best corrected visual acuity (BCVA) between 73 and 24 letters on ETDRS
• CNV lesion size > 50% of the total lesion size

Major exclusion criteria:

• No previous treatment for AMD
• No active peri-, ocular, or intraocular infection at baseline; history of recurrent or active ocular or intraocular inflammation (IOI)
• Diabetic retinopathy, diabetic macular edema or retinal vascular disease other than AMD
• Any Prior anti VEGF use, regardless of indication
• History of ocular surgery (pars plana vitrectomy, sub macular surgery, glaucoma surgery)

RANDOMIZATION SCHEME AND INTERVENTIONS

Randomized 1:1:1 to

1. (a) 2 mg abicipar (week 0,4,8, then Q8 weeks)
2. (b) 2 mg abicipar (week 0, 4, 12, then Q12 weeks)
3. (c) 0.5 mg ranibizumab Q4 weeks

MECHANISM OF ACTION

DARPin: synthetic binding proteins made up of ankyrin repeat domains

Abicipar: pegylated DARPin anti VEGF therapy that binds to all isoforms of VEGF A, which is a small molecule with a high binding affinity with a half-life of 13 days in the aqueous humor

All participants attended monthly visits with clinical examination, BCVA via ETDRS, and optical coherence tomography (OCT). Medication was withheld if study eye experienced a peri-ocular or intraocular infection. Each dose was administered with a 0.05-ml intravitreal injection. In the event of ocular or periocular infection, a new retinal break or retinal detachment, or intraocular pressure of 30 mmHg or higher in the study eye, dosing was withheld until the event resolved

PRIMARY ENDPOINT

• Proportion of patients with stable vision (loss of <15 letters) at week 52
• * Lower limit of nonferiority was a minimal change of -5.0 letters at week 52

SECONDARY ENDPOINTS: evaluated over 104 weeks

• Proportion of patients with stable vision (as defined above) at 104 weeks
• Mean change in BCVA from baseline
• Proportion of patients with at least a 15 letter improvement in NCVA from baseline
• Mean change in central retinal thickness
• Change in NEI-CFQ-25 compositie score

RESULTS

Study population

• 1888 patients enrolled
• 1411 (74.7%) completion rate at 104 weeks and included in study: abicipar Q8 (n=443), abicipar Q12 (n=442), ranibizumab Q4 (n=520) * The “completor population” was used for the final analysis
• 8.9% abicipar-treated patients discontinued treatment during study due to intraocular inflammatory events (IOI)

PRIMARY OUTCOME: Proportion of patients with stable vision (<15 letter loss) at 52 weeks

• There was no difference in the proportion of patients that maintained stable vision between abicipar Q8 OR Q12 compared to ranibizumab Q4

SECONDARY OUTCOMES

• There was no difference in the proportion of patients with stable vision among all 3 groups at week 104 (93% abicipar Q8, 89.8% abicipar Q12, 94.4% ranibizumab Q4)
• Mean number of injections in the 2nd year (week 104): 6 (abicipar Q8), 4 (abicipar Q12), 11 (ranibizumab Q4)
• There was no difference in the overall mean gain in BCVA, mean gain of > 15 letters or more, or mean CRT change between raninizuamab and abicipar Q8 or Q12
  • Mean gain in BCVA was maintained at 52 week and 104 weeks among treatment groups (+7.8 letter abicipar Q8, +6.1 abicipar Q12, +8.5 ranibizumab Q4)

Adverse events

• There was no difference in any adverse event (AE) among the groups overall
• There were significantly higher rates of ocular AEs in the abicipar Q8 group (17.6%), abicipar Q12 group (22.5%) than in the ranibizumab Q4 group (6.4%)
  • Rates of IOI were 16.2% (abicipar Q8), 17.6% abicipar Q12, and 1.3% in the ranibizumab Q4 group
  • However, there was a lower rate and no significant difference in new IOIs between week 52 weeks and week 104 among all 3 groups (0.8% abicipar Q8, 2.3% abicipar Q12, 1.0% ranibizumab Q4). The highest risk occurred in the first 12 weeks with a 2.95% monthly rate within the first 12 weeks, then 1.13% between week 12-24, and 0.21% in the second year (week 48-104).
• Severe vision loss of >30 letters occurred significantly more frequently in the abicipar group: 5.3% abicipair Q8, 5.9% abicipar Q12, compared to 2.2% ranibizumab Q4

Conclusions

• Abicipar Q8 or Q12 intervals were noninferior to the ranibizumab Q4 interval at week 52 for maintaining stable vision and BCVA change from baseline (primary endpoint). This essentially held true at week 104, but that was not the primary endpoint
• There were significant higher rates of IOI in the abicipar groups compared to ranibizumab