Novel Drug Delivery System for the Management of Wet AMD - Episode 6
Retina specialists provide insight into the patient selection and safety concerns with the innovative Port Delivery System (PDS) that offers a new means of sustained anti-VEGF therapy.
Carl Regillo, MD: We’ve just talked about this great safety profile.
Diana Do, MD: Exactly. That’s what I want to ask you. Are there any safety concerns with the Port Delivery System? This indwelling implant seems great, gives this drug, but are there any concerns?
Carl Regillo, MD: Yes. It would be unrealistic to think you’re going to get the exact same safety profile; it’s just unrealistic. You’ve got a foreign device in the eye. You’ve got a surgical procedure. The good news is most of the adverse events associated with the device, the surgery, the refill and so forth, most of that is within the first year. When we think of adverse events and safety profile, to compare apples to apples, we have to think about the safety profile of many intravitreal injections in a patient over the course of 5, 6, 7 years in the real world of getting injections. The rate of infection may be only 1 in 3000 per injection, but the cumulative rate of endophthalmitis for a patient undergoing 5 or more years of many injections could be up to 1%. In the trial, what were the adverse events associated with the device? It was vitreous hemorrhage, most of that was postoperative, most of that was mild, most of it went away on its own, about 5% or 6%. There was erosion or retraction of the conjunctiva over the device. That’s not good because it requires surgical repair. It puts the patient at risk for endophthalmitis, a serious intraocular infection. The rates of those were in the 4% or 4.5% range that necessitated usually a trip back to the OR [operating room] to repair. And there was an endophthalmitis rate, 4 patients in the clinical trial. All of it occurred early on for the most part within the first year, and the rate was about 1.5%. It doesn’t sound as good as 1 in 3000, but for over 18 months the intravitreal injection arm also had a case of endophthalmitis, so the rate effectively per patient was 0.6%. You can see over time it is becoming a little bit more equal. The device can still have issues or complications like dislocation later on. Fortunately those are rare.
So, the safety profile overall, I think most people would say it’s acceptable, looks pretty good considering what it is. For some patients, I think that’s a reasonable trade off when it comes to the potential benefits of having that sustained release in very few injections or manipulations and even potentially office visits over time. What do you think of the surgery? You’re a vitreoretinal surgeon, you’re going to potentially put this in. It’s through phase 3, it could be commercialized and FDA approved in our hands within the next year or two. You’re going to use it; what do you think?
Diana Do, MD: I love surgical innovation, and certainly this device, Port Delivery System [PDS], is an out of the box way to develop a sustained delivery system. So, it seems very exciting. The surgical implant, based on the videos and the early clinical trial experience, looks very straightforward as long as you follow the recommended steps to mitigate any potential postoperative vitreous hemorrhage, and of course to appropriately cover the implant at the end of the case. I think there is a role for this implant in select patients. The question many retina specialists will have is, after you implant the PDS system, how often do you need to see patients? Do you implant and then have them come back in 6 months, or would you follow them more closely, Carl?
Carl Regillo, MD: At first, definitely follow more closely. Again, most of the issues, the adverse events, complications are occurring within the first few months. You want to get through the perioperative period, the first 6 to 8 weeks for sure, seeing the patient a few times. Thereafter, I think what’s going to happen is I’ll probably see the patient every 2 months and then maybe every 3 months. I’ll try to get a feel for when they need a refill because I may not necessarily refill the device on the clock every 6 months, and really put it to the test for a given patient. I do want to say that we learned a lot about the surgical approach and how to mitigate these complications, going from phase 2 and through phase 3. We’re still learning. We’re looking back at all the videos from all the surgeries in the clinical trials. I think we can do better and bring down some of these complicate rates, including infection, conjunctival issues, and so forth. There has already been good progress in that way, especially with regard to hemorrhage. Hemorrhaging was a big problem in phase 2 early on, and then surgical technique modification took place, and further modifications are being recommended now, which I do think is going to help make this a very acceptable approach from a safety standpoint for our patients. What type of patients do you think you’re going to use it in? If it’s in your hands, you’re comfortable with it, you’ve been trained on it. What’s the ideal patient?
Diana Do, MD: Certainly I don’t think it’s a first-line treatment, because many patients who come in with new onset wet macular degeneration, we want to treat them rapidly and that day, usually in the office. So, those patients will receive an intravitreal medicine. I think for the Port Delivery System, I’ll probably select patients who I know are responsive to anti-VEGF agents and who are doing well, and for whom I want to maintain the benefits, but stretch out the intervals. Of course, these patients have to have healthy conjunctiva, no other issues like glaucoma or things that might necessitate other surgeries that involve the conjunctiva in the future. But I still am trying to determine exactly what would be the best patient population for this. What are your recommendations, Carl?
Carl Regillo, MD: I agree. We throw around this term frequent fliers, those patients for whom we can’t extend the treatment interval with our drugs that we’re using now with intravitreal injections in the office, the ones who need to get it every 4, 6, or even 8 weeks. There may be a patient interested in getting injections less frequently, but you’re right. We’re going to start doing injections. We’re going to see what the patient’s individual needs are, and we probably are going to self-select. The patient will be much more inclined to want to do this if they can’t break out of a frequent, every 4-, 5-, 6-week routine. This could go on for years. That’s the type of patient to whom we’re most inclined to want to offer the device and the patient most inclined to accept it. I think it’s going to be a good tool to have in the tool chest, if you will, for patients who want something more durable.
Carl Regillo, MD: Thank you for watching this HCPLive® Peers & Perspectives®. If you enjoyed the content please subscribe to our e-newsletter to receive upcoming Peers & Perspectives® and other great content right in your inbox.
Transcript Edited for Clarity