Treatment of wet AMD-related vision loss is an onerous task for patients and eye doctors alike, typically requiring monthly injections of blood vessel-blocking eye drugs such as Genentech's Lucentis. The time and discomfort those therapies entail can drive patients to slack on adherence and allow their vision to grow worse. Now, an eye implant that continuously releases a tweaked formulation of Lucentis could save those patients months between eye doctor visits and lead to better vision gains in the long term, too.
Citing data from a recent late-stage trial, the Roche subsidiary says its Port Delivery System with ranibizumab (PDS) is a potential boon for patients with neovascular or "wet" age-related macular degeneration (nAMD), one of the leading causes of blindness in the U.S. The drug inside the PDS isn't exactly new—it's an altered formulation of ranibizumab, or Lucentis, approved since 2006 to treat a host of retinal diseases—but the delivery system is.
Genentech's PDS platform is a permanent implant, roughly the size of a grain of rice, that continuously releases a customized formulation of ranibizumab into the eye. The device is refilled every six months.
An anti-vascular endothelial growth factor (VEGF) therapy, ranibizumab thwarts the development of leaky blood vessels that cause vision loss in nAMD patients. The version of the drug in the Port Delivery System isn't FDA-approved, the company said in a release, but it serves the same function as injected Lucentis.
By delivering medication automatically over long stretches of time, the PDS may help wet AMD patients avoid frequent trips to eye clinics and maintain long-term vision gains through better adherence.
"The current standard of care for nAMD can be burdensome for patients and their caregivers because it requires patients to visit their ophthalmologist for eye injections of anti-VEGF therapy as often as (once) a month to help maintain vision gains and/or prevent vision loss," Dr. Christopher Brittain, vice president and global head of ophthalmology product development at Genentech, said in an email. "This high treatment burden of anti-VEGF therapy can lead to under-treatment of nAMD and, potentially, less than optimal vision (outcomes)."
Lucentis is already the standard treatment for age-related macular degeneration and other retinal conditions like diabetic macular edema, retinal vein occlusion and diabetic retinopathy. According to Brittain, no other therapy has outperformed monthly ranibizumab injections in curbing nAMD-related vision loss.
Now the company is touting recent phase 3 data that showed its PDS worked about as well as Lucentis and allowed patients to wait up to half a year before their next treatment. In Genentech's nAMD Archway trial, 98.4% of PDS patients were able to go six months without needing additional therapy and achieved improvements in sight on par with the ranibizumab injection arm.
After 36 weeks and 40 weeks, participants given eye injections of ranibizumab scored slightly better in best-corrected visual acuity testing, a standard measure of visual improvement; PDS patients turned out non-inferior results, but crucially, achieved and maintained those sight gains with a single ranibizumab refill over six months.
For patients who already rely on Lucentis injections, the ease of treatment Genentech's PDS platform provides could still make it a clear winner in terms of long-term vision improvement.
"Real-world studies on patients treated with anti-VEGF therapy have consistently demonstrated outcomes that do not meet those seen in the pivotal studies," Brittain said. "By reducing this treatment burden, PDS may offer more reliable improvements in, and maintenance of, vision for people living with nAMD.
Overall, the PDS-administered drug boasted safety equivalent to monthly ranibizumab injections. The surgical procedure to insert the device was generally well-tolerated, with the majority of side effects manageable and in-line with expectations, Brittain said. The company is running another trial to study the long-term safety and tolerability of the PDS as a wet AMD treatment.
Armed with those results, PDS could slash nAMD therapy visits from as many as 12 per year to two per year, Brittain said.
The company hasn't pinned down a filing timeline for the implant, Brittain added, but Genentech aims to submit the phase 3 results to the FDA and other drug regulators to deploy its PDS "as soon as possible."
Beyond the realm of nAMD, Genentech is recruiting patients for a separate study of its Port Delivery System in diabetic macular edema, which can cause blindness in patients with diabetes. Lucentis already has a nod for that condition, making the indication a natural fit for the PDS.
As for the future of the PDS, Genentech plans to develop new drugs specifically designed to work with its Port Delivery Platform, Brittain said. The company is the early stages of development for a PDS-friendly version of the anti-Ang2/anti-VEGF molecule dutafab, which functions similarly to faricimab—a bispecific antibody developed by Genentech to fight wet AMD.