Carl Regillo, MD, takes us through the history of the port delivery system, from ideation to FDA approval.
At ASRS 2021, Carl Regillo, MD, presented the ASRS Founders Award lecture: “The Journey of the Port Delivery System.” In his lecture, he detailed the 21-year history of the therapeutic device, from ideation to then-pending FDA approval.
Dr. Regillo is the director of the Wills Eye Retina Service as well as professor of ophthalmology at Sidney Kimmel Medical College at Thomas Jefferson University.
This video was recorded at the ASRS 39th Annual Scientific Meeting in San Antonio, on Sunday, October 10, 2021. Since the recording, the port delivery system (PDS) with ranibizumab (Susvimo, Genentech) has been approved by the FDA.
Carl Regillo, MD: Hi, I'm Carl Regillo, director of the retina service at Wills Eye Hospital in Philadelphia. It was a great honor to receive the ASRS Founders Lecture. The American Society of Retina Specialists is the largest retina organization in the world, representing over 3000 retina specialists in over 63 countries. And so it's a tremendous honor and privilege to be able to give this lecture.
And the topic of my lecture, what I chose was the journey of the port delivery system (PDS), about 21 years in the making now, and on the cusp of FDA approval. I got involved in the development of port delivery system somewhere between phase one, phase two. So fairly early on in the development, and I've had a long-standing interest in drug delivery.
And what we have now is we have some excellent therapeutics, anti-VEGF drugs that we inject in the eye; and they work very well, very safe, but they're not very durable. Patients have to come in frequently to get injections to get good outcomes, especially for wet AMD.
So what this is, of course, is sustained delivery of anti-VEGF, and holds the promise of both decreasing the burden of patients having to come to the office for these injections, and also potentially getting better long-term vision outcomes, which is hard to do in practice, again, with a drug that you have to deliver on a very frequent basis.
The lecture really focused on two things. One, it took a long time to get where we needed to be, right now, on the cusp of the FDA approval. And it took a lot of people, a lot of resources, and a lot of collaboration to make this a very successful program that it is.
So turn the clock back 21 years ago, that's when the idea first came about. Eugene de Juan is credited with coming up with the idea of a port delivery system, sustained-release approach. And at the time, the anti-VEGF era was just starting to take hold; it was in testing, it wasn't even commercially available yet. And the idea of the device, which was disclosed in the year 2000.
The device really didn't go really anywhere for a while. But as anti-VEGF therapy finally became FDA-approved and on the scene and commercialized, we started to use it circa 2006. That's prompted the PDS to start to move along.
It was about 2010, when it was licensed to a company called ForSight Vision4, that's when things really kicked into high gear. So at that point, the PDS was put to the test, in the preclinical stage to see how well it could work, proof of concept for sustained delivery, and allow it to be determined if it was going to be a reliable way to deliver the drug. And it looked promising, so it went into phase 1 testing.
And the phase 1 clinical trial took place at one center outside the United States. And it was also pretty good. There were certainly safety issues because it was a new surgical procedure, a new device. And that's another big part of the story.
Overcoming hurdles with complications and issues associated with the device as it went from phase 1 to phase 2, phase 3. And that's where a lot of smart people got involved to overcome problems.
Such as early on in phase 2, for example, there were initially high rates of vitreous hemorrhage, unacceptably high, the study was actually paused. And the surgical technique was modified in such a way that the hemorrhage rate came way down to a very acceptable level, and other complications and adverse events associated with the device, the surgery and so forth, with each and every stage of testing actually got better.
And when it came time for phase 3 testing, the Archway study, we got the results we were hoping for in terms of how the how the device worked to deliver anti-VEGF therapy in a continuous and effective way for at least six months, and the complication rates associated with insertion of the device was kept down. And really the, the heart and soul of the talk was, again, how long it took to get to this point, and how many people involved—a lot of smart people and a lot of great collaboration between retina specialists and basic scientists—to allow this to be a successful program.
The American Society of Retina Specialists (ASRS) hosted its 39th Annual Scientific Meeting from October 8-12, 2021, at the JW Marriott San Antonio Hill Country Resort and Spa in San Antonio, Texas.
According to ASRS, its 2021 scientific program offered attendees innovations in retina science, clinical practice, and surgery with 148 papers, 165 posters, 46 papers on demand, and 69 films, as well as a wide range of networking opportunities and the chance to exchange ideas and perspectives with peers.