Drug-delivery device implant works well for neovascular AMD

An ocular implant that continuously dispenses an antivascular endothelial growth factor (anti-VEGF) therapy into the vitreous performs well in the management of neovascular age-related macular degeneration (nAMD), affording disease control and achieving vision and anatomical outcomes similar to that obtained with monthly intravitreal injections, as shown in the phase III ARCHWAY trial.

Known as the Port Delivery System (PDS), the investigational drug delivery system is a surgically placed permanent ocular implant. Aside from continuous delivery of treatment, PDS has an implant reservoir that can be repeatedly refilled. Drug replenishment is performed via clinic-based refill-exchange procedures.

In the current analysis, the primary endpoint of change in best-corrected visual acuity (BCVA) score from baseline to week 40 was 0.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the PDS arm as opposed to 0.5 in the monthly ranibizumab injection arm. The difference established noninferiority and equivalence of the drug delivery device (–0.3, 95 percent confidence interval [CI], –1.7 to 1.1). [Ophthalmology 2021;doi:10.1016/j.ophtha.2021.09.016]

“ARCHWAY represents the first successful phase III trial of a permanent ocular implant for the treatment of nAMD,” the investigators said.

With refill exchanges performed every 6 months, more than 98 percent of PDS-treated patients were able to maintain disease control without supplemental treatment, they added. This indicates the “potential for the PDS to reduce the overall treatment and monitoring burden in clinical practice.”

In terms of safety, more ocular adverse events occurred in the PDS than in the ranibizumab injection arm. This was as expected, according to the investigators, given the surgical procedures involved with the PDS.

Prespecified ocular adverse events of special interest (AESIs) were reported in 19 percent of patients in the PDS arm relative to 6 percent of patients who received monthly ranibizumab intravitreal shots. Ocular AESIs in PDS-treated patients included endophthalmitis, retinal detachments, vitreous haemorrhages, and conjunctival erosions or retractions. Most of them occurred within 1 month of implantation.

ARCHWAY included 418 nAMD patients (mean age 75 years, 59 percent female). Of these, 251 patients were randomized to treatment with the PDS (ranibizumab 100 mg/mL with fixed 24-week refill-exchanges) and 167 to receive intravitreal ranibizumab injections (0.5 mg injections every 4 weeks).

Mean time since nAMD diagnosis was 5.6 months, and the patients had good vision at baseline. The mean BCVA was 74.4 ETDRS letters in the PDS group and 75.5 ETDRS letters in the ranibizumab injection group (approximate Snellen equivalent 20/32). All patients had been previously treated with and responsive to anti-VEGF therapy (five injections on average).

Based on the PDS patient experience assessment conducted at week 40, the vast majority (93.2 percent) of the patients with the ocular implant preferred ranibizumab as delivered via the PDS as opposed to intravitreal injections. This was despite monthly visits for monitoring.

“Supported by a strong patient preference over intravitreal injections, the PDS has the potential to help reduce frequent visits for treatment and improve vision outcomes in patients with nAMD in clinical practice compared with real-world studies,” the investigators said.

Currently, the PDS is also being investigated for the treatment of diabetic macular oedema and diabetic retinopathy. The investigators believe that the device can fundamentally change the way VEGF-mediated retinal diseases are treated in the future.