The US Food and Drug Administration for the first time approved an implant to treat neovascular age-related macular degeneration (nAMD).
By releasing a constant dose of ranibizumab, the implanted port delivery system (Susvimo) made by Genentech/Roche reduces the number of antivascular endothelial growth factor (VEGF) injections needed to maintain patients’ visual acuity.
“The Susvimo platform really represents a transformative approach to sustain VEGF suppression in patients that need it for a long period of time with dramatically reduced treatment burdens,” said co-investigator Lloyd Clark, MD, an assistant clinical professor at the University of South Carolina School of Medicine in Columbia.
However, in the pivotal Archway trial, the device caused more adverse events than monthly ranibizumab injections — particularly endophthalmitis — leading some experts to voice caution.
“You wouldn’t necessarily think about this port delivery system as a primary therapy,” said Timothy Murray, MD, a retina specialist and founding director/CEO of Ocular Oncology and Retina in Miami, Florida, who was not involved in the trial. He expects to recommend it only to patients who need lots of injections, or those who are having trouble getting injections frequently enough. One example would be patients who are not well enough to come to his office.
In addition, at least for now, implanting the device must take place in a hospital or outpatient surgery center, which could make it a more expensive treatment, Murray said.
A Genentech/Roche spokesperson said the company anticipates coverage by Medicare, is working with other payers, and expects the device to be available “in the coming months.”
VEGF has been highly effective in the treatment of patients with nAMD, and the rate of adverse events has been low. However, many patients require injections every few weeks to maintain their visual acuity. Intravitreal injections are uncomfortable, and many patients find it difficult to get to their many appointments.
The port delivery system, which is slightly longer than a grain of rice, is implanted in the pars plana during a surgical procedure performed in an operating room with local anesthesia. Once implanted, the device — which continuously diffuses ranibizumab into the vitreous cavity — remains covered indefinitely by the Tenon capsule and the conjunctiva.
Every 24 weeks, the clinician uses a customized needle to refill the implant with ranibizumab 100 mg/mL. This office-based procedure is slightly more complicated than an intravitreal injection because the needle must be perpendicular to the implant, and directly in its center.
For Archway, 248 participants were assigned to receive the implant and 167 to receive intravitreal injections with ranibizumab 0.5 mg every 4 weeks. Participants had received, and showed benefit from, a mean of five intravitreal injections before enrollment.
Maintenance of vision — measured as change between baseline and best-corrected visual acuity (BCVA) — was equal in the two treatment groups. Anatomical results were also similar. And in the latest extension of the trial, vision and anatomic results were maintained up to 72 weeks with refills every 24 weeks in the port delivery group.
Only 2% needed refills earlier than planned in the first 24 weeks, and 5% needed them early in the next 24 weeks.
Over an average of 79 weeks, 35% of patients in the port delivery group had ocular adverse events deemed related to the treatment, vs 9% in the monthly injection group. Four patients (1.6%) in the port delivery group had endophthalmitis, vs 1 (0.6%) in the monthly injection group.
Even this rate reported for the monthly injection group is high, Murray said; most retina specialists giving intravitreal injections have an endophthalmitis rate of one per 5000 to 10,000 injections. “What that means is that most patients would never experience endophthalmitis.”
Most of the patients who developed endophthalmitis with the port delivery system had conjunctival abnormalities after it was implanted, Clark said. “We made significant adjustments to the surgical procedure in terms of conjunctival closure, which have addressed many of these.”
Murray was encouraged to note that only 15 patients (6%) in the port delivery group vs 6 (3.6%) in the monthly injection group had vitreous hemorrhage. This complication was higher in earlier studies, he said.
“I think we’ve got a good handle on that,” Clark said.
In three patients, the port delivery system dislocated during the refill procedure. The clinicians may have applied too much pressure to the refill needle, Clark said. And analyzing the dislocated devices, the researchers found the incisions in the sclera made during implantation were slightly longer than the recommended 3.5 mm.
“I don’t think we have a perfect product in terms of the safety profile under phase 3 clinical trials, but I think with careful surgical technique, adequate training, and evolution of the procedure, there’s hope and optimism that the risk profile will improve,” Clark said.
Clark reports financial relationships to Genentech, Regeneron Pharmaceuticals, and Kodiak Sciences. Murray reports financial relationships with Regeneron and Alcon Surgical. The study was independently supported.
Laird Harrison writes about science, health, and culture. His work has appeared in national magazines, in newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at lairdharrison.com or follow him on Twitter@LairdH