Despite demonstrated noninferiority of the long-term ranibizumab Port Delivery System (PDS) compared to monthly intravitreal ranibizumab treatments for neovascular age-related macular degeneration (AMD), the implant appears to have greater likelihood of adverse events that may impact its value.
Study design
This was a phase 3, randomized, multicenter, open-label, noninferiority study comparing the PDS with ranibizumab to monthly intravitreal ranibizumab for the treatment of neovascular AMD. All patients enrolled in the study had neovascular AMD and demonstrated prior improvement with anti-VEGF treatments. Patients in the PDS group received ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks, and patients in the intravitreal group received ranibizumab 0.5 mg injections every 4 weeks (monthly), for a total treatment time of approximately 2 years. The primary outcome was the change in BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline, averaged over weeks 60 and 64 and weeks 88 and 92, with a noninferiority margin of 3.9 ETDRS letters.
Outcomes
Compared to patients in the monthly ranibizumab group, patients in the PDS group had a noninferior mean change in BCVA score from baseline of +0.4 and –0.6 ETDRS letters averaged over weeks 60 and 64 and 88 and 92, respectively. There was a clinically insignificant difference of 11.3 μm (95% CI, −0.1 to 22.6) in the central point thickness change from baseline to 2 years when comparing the PDS and monthly ranibizumab arms. Less than 6% of patients in the PDS group required treatments prior to the scheduled 24-week port refill during each of the 6-month intervals in the study. Though both groups reported adverse events, a greater number of significant events were reported in the PDS arm: 4.0% of PDS patients experienced conjunctival erosions, 2.4% experienced conjunctival retractions, 1.6% experienced endophthalmitis, and 1.6% experienced implant dislocations.
Limitations
The prespecified treatment criteria in the PDS arm in the study may not mirror real world treatment criteria.
Clinical significance
The PDS implant is effective at delivering sustained-release anti-VEGF in patients with neovascular AMD. However, the adverse events, especially the high rate of endophthalmitis, would make it a viable option for only a small subset of neovascular AMD patients. Furthermore, this particular device is currently recalled and not available due to an issue with septum dislodgement. Additional focus on surgical experience and optimization as well as device modifications may reduce some of the device-related adverse events in the future and improve the value of this type of delivery system as a treatment option.
Financial Disclosures: Dr. Ajay Kuriyan discloses financial relationships with Adverum, Annexon, National Eye Institute (Grant Support); Alimera Sciences, Allergan, Bausch + Lomb, EyePoint Pharmaceuticals, Novartis, Alcon Pharmaceuticals (Consultant/Advisor); Genentech (Consultant/Advisor, Grant Support); Lumata Health (Consultant/Advisor, Private Equity/Stock Holder); Optos, Spark Therapeutics (Lecture Fees/Speakers Bureau); Recens Medical (Consultant/Advisor, Private Equity/Stock Holder).