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Margaret Chang, Katie Maass, Galin Jackson Spicer, Natasha Singh, Steven Blotner, Mauricio Maia; Immunogenicity profile of the Port Delivery System with ranibizumab in patients with nAMD. Invest. Ophthalmol. Vis. Sci. 2021;62(8):227.
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The Port Delivery System with ranibizumab (PDS) is an investigational drug delivery system for the continuous intravitreal release of ranibizumab (RBZ) via a permanent indwelling intraocular implant. The phase 2 Ladder and phase 3 Archway trials demonstrated that treatment with PDS with a customized formulation of RBZ 100 mg/mL (PDS 100 mg/mL) was generally well tolerated and had comparable efficacy to monthly intravitreal RBZ. Immunogenicity is important in assessing safety and efficacy of recombinant therapeutics and was monitored in both trials.
Ladder (NCT02510794) patients (pts) were randomized to PDS with RBZ 10, 40, or 100 mg/mL, or monthly intravitreal RBZ 0.5 mg (monthly RBZ). Archway (NCT03677934) pts were randomized to treatment with PDS 100 mg/mL with fixed 24-week refill exchanges (Q24W) or monthly RBZ (Q4W). As both trials enrolled pts with nAMD responsive to anti-VEGF treatment, immunogenicity analyses focused on incidence of treatment-emergent (TE) anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs). We report ADA status in Ladder (end of study) and Archway (primary analysis) and the impact of ADA status on serum PK at week 24, and on visual and safety outcomes at week 40 in Archway.
In Ladder, there was no apparent dose response on incidence of TE-ADAs across PDS arms (6.9%-15.3%). Incidences of TE-ADAs with PDS 100 mg/mL were relatively low in Ladder (15.3% [9/59]) and Archway (11.7% [29/247]), and comparable or slightly higher than monthly RBZ (Ladder: 14.6% [6/41]; Archway: 5.5% [9/164]). Overall incidences of TE-NAbs were low with both monthly RBZ and PDS 100 mg/mL (Ladder: 0%-3.4%; Archway: 2.4%-5.3%). In Archway, over 40 weeks, presence of ADAs in PDS 100 mg/mL pts did not appear to impact mean (95% CI) change from baseline in BCVA versus ADA negative pts (0.0 [-2.8, 2.8] vs 0.2 [-1.0, 1.5] ETDRS letters, respectively) or postoperative (>37 days) incidence of ocular AEs (41.2% [14/34] vs 38.0% [81/213]), intraocular inflammation (including endophthalmitis; 2.9% [1/34] vs 5.6% [12/213]), or iritis (0% [0/34] vs 1.4% [3/213]); there was no apparent trend for an effect of ADA status on serum PK or incidence of non-ocular AEs.
The immunogenicity profile of PDS 100 mg/mL was comparable to that of monthly RBZ, with no apparent impact of ADAs on outcomes. These data further support the efficacy and tolerability of PDS 100 mg/mL Q24W in nAMD.
This is a 2021 ARVO Annual Meeting abstract.
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