Port Delivery of Ranibizumab  Maintains High Efficacy at 2 Years in Phase 3 Trial

Port delivery of ranibizumab is no less effective than monthly injections of the anti vascular endothelial growth factor (VEGF) treatment for patients with neovascular age-related macular degeneration (nAMD), according to findings of a 2-year trial published in Ophthalmology. The investigation reviewed patients treated with the use of the Port Delivery System (PDS) refilled once every 24 weeks compared with those given monthly injections and found the implantable device is noninferior to conventional treatment.

The open-label trial, Archway (ClinicalTrials.gov Identifier: NCT03677934), included 415 patients with nAMD randomly assigned to receive treatment with either PDS, refilled at 24 weeks, or monthly intravitreal injections (IVI) of ranibizumab (248 in the PDS group; 167 in the IVI group)

The researchers assessed patients best-corrected visual acuities (BCVA) throughout the course of the study, with any change from baseline averaged across weeks 36 and 40 being the primary end point. Patients treated with port delivery of ranibizumab and IVI both  underwent spectral-domain optical coherence tomography (SD-OCT) examination at follow up visits. Clinicians also assessed them for any ocular and nonocular adverse events, and pharmacokinetic (PK) outcomes (serum ranibizumab concentrations and aqueous humor ranibizumab concentrations) using serum samples collected from all patients at weeks 4, 24, 36, and 96.

Most patients managed with port delivery of ranibizumab needed no supplemental treatment during 4 therapy intervals: 98.4%, 94.6%, 94.8%, and 94.7%, respectively. Structural outcomes measured with SD-OCT were similar between the 2 arms at week 96. From baseline, average central subfield thickness (CST) change was less than 15 µm apart in the groups, including any foveal pigment epithelial detachment. Center point thickness total change, in mean (standard error) with PDS was 9.9 (SE 3.64) µm, and, for IVI, it was -1.3 (SE 4.48) µm.

Adjusted difference in BCVA from baseline — averaged between weeks 88 to 92 — was -1.1 ETDRS letters (SE 0.61 letters) for patients given port delivery ranibizumab, compared with -0.5 (SE 0.75) letters in the monthly injection group. Because intergroup difference was within 3.9 early treatment diabetic retinopathy study (ETDRS) letters, meeting 95% confidence intervals, port delivery ranibizumab refilled once every 24 weeks proved noninferior to intravitreal injections.

“Although a slight decrease in serum concentrations was observed before each refill-exchange procedure, the concentrations remained above the trough concentration observed in the monthly ranibizumab arm,” the investigators explain. “Together these data show that the PDS implant is continuously and consistently delivering ranibizumab at therapeutic levels.” 

Among the adverse events of special interest (AESI), 23.8% occurred in patients with port delivery of ranibizumab, and 10.2% for IVI ranibizumab. Cataracts developed more often than other AESI in either group; for 8.9% with PDS and 6.0% receiving injections. Other adverse events for those undergoing port included 4.0% with conjunctival erosion, 2.4% conjunctival retraction, 1.6% implant dislocation, and 1.6% endophthalmitis. An incision length at implant insertion exceeding 3.5 mm to 3.7 mm is believed to be a main factor in dislocation. Three septums dislodged, prompting a voluntary recall, but refill-exchanges continue in US clinical practice.

Limitations of this trial include a specific patient population diagnosed within 9 months who showed prior response to anti-VEGF therapy, and were followed for a 96-week period only. However, a comparable amount of AESIs occurred in both arms after initial port refill-exchange, ”suggesting that the safety profile of PDS is greatly influenced by the initial surgery,” according to the investigation.

Disclosures: This trial was supported with funds from Genentech, Inc., also involved in conduct of the study. Several investigators have disclosed affiliations with Genentech, and/or the biotech, medical device, or pharmaceutical industries. Please see the original reference for complete disclosures.