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Advances in the Clinical Management of Diabetic Macular Edema and Age-Related Macular Degeneration - Episode 11

Exploring the Potential for a Novel Port Delivery System for DME

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Carl D. Regillo, MD, FACS; Blake Anthony Cooper, MD, MPH; Michael A. Klufas, MD; and David R. Lally, MD, consider the utility of a novel port delivery system for the delivery of anti-VEGF treatment.

Carl D. Regillo, MD, FACS:Mike we now have the port delivery system [PDS], approved in neovascular age-related macular degeneration [AMD]. It’s also in clinical trials for the treatment of diabetic macular edema [DME] and diabetic retinopathy, so it could get this broad label and be used potentially quite extensively. Tell me about what these studies show thus far––it’s going to be mainly the AMD studies because we don’t have any data yet for diabetic retinopathy and diabetic macular edema [DRDME]––but tell me a bit more about adverse events, safety concerns in ways we can mitigate that.

Michael A. Klufas, MD: Great question. One of the main safety concerns and which is also on the label of the port delivery system or ranibizumab [Susvimo] is…a black box warning for endophthalmitis. We have been able to mitigate this adverse effect by careful handling of the conjunctiva closing device with Tenon layer and conjunctiva to prevent retraction and exposure over time. We are also effective in treating it. The device can be irrigated with vancomycin. A traditional tap and inject can be performed as well and we have even explanted and exchanged, put another device in some of these eyes if that’s clinically indicated. In terms of other safety risks, we have to be careful of incision length too. We know the incision length has been shortened over time to prevent dislodgement of the device into the vitreous cavity. Although that’s a complication, it can be managed as well and a new device can be replaced with sutures to support the incision to make it a bit smaller. As Dr Cooper was mentioning, we’ve done about 500 of these devices in the clinical trials and that will increase over time but if you look at the average number of cases, for most investigators, they are somewhere between 2 to 10 cases maybe, so as we get more experience we are hoping that many of these complications will go down in rates over time. Then we can make it a comparatively safe procedure as well.

Carl D. Regillo, MD, FACS: It’s important to talk a bit more about the surgical technique. It’s been mentioned several times that that’s an important aspect of keeping adverse effects or adverse events associated with the device itself down to as low as possible. Some have said now that it is commercialized, it’s potentially in a lot of hands for retinal surgeons in the United States and maybe even worldwide that we’re going to see increased rates of complications. I think the opposite; I think with further refinements and more knowledge that we have gained over time in the trials and now in practice, we have the potential to reduce the adverse events. As you said, the way we handled conjunctival and Tenon, we are doing a better job now than we did in the early-phase studies. We are both part of those clinical trials. It’s promising, but patients need to understand they do assume an increased risk of unique adverse effects or some not so unique but more highly associated with devices like infection and vitreous hemorrhage. You can get some of these complications with injections, but it’s much less common.

Michael A. Klufas, MD: Good point. And if we look at the earlier trials like the LADDER trial [NCT02510794], vitreous hemorrhage was quite common and they investigated that, and now we perform laser ablation to the pars plana prior to entering and that reduced the risk of that quite a bit. We’re going to keep learning about the device and how it fits into our treatment paradigm. It’s great to have another option for our patients. Personally, the patients I had in the trials and offer the therapy to, they don’t like the injection process. They are tied to the device once they have it and they are happy and their quality of life is quite improved.

Carl D. Regillo, MD, FACS: As I say, injections are generally well tolerated but patients don’t like them and would rather not have them. As you said, some patients are averse to them and so it represents a nice alternative for patients than the traditional “come to the office and get your intravitreal injection.”

Blake Anthony Cooper, MD, MPH: I also think that it’s going to be important as we move forward that we may be able to put something else in the device, so the device is the way that we can administer other forms of medication in the future.

Carl D. Regillo, MD, FACS: Right, it’s a platform. And although right now we technically can’t put anything else in it because the device is specifically designed for antibody fragment ranibizumab, it could be other antibody fragments in development or in the future that could work as well or even better in this device.

Dave, how do you think PDS is going to impact patient quality of life and disease outcomes?

David R. Lally, MD: I anticipate it’s going to have a dramatic improvement in my patients’ quality of life, starting with my patients with neovascular AMD. These patients require lifetime therapy, typically, when therapy is initiated. As we have discussed before, the treatment burden is quite high and I find a lot of my patients have anxiety the day before they are coming to the office, knowing they’re about to get a needle in their eye. For these elderly patients after the injection, a lot of times the ocular surface is irritated, dry. They are even more blurry and irritated, and that can last for a few days from all the topical anesthetics and cleaning agents that we use to administer the intravitreal injection. For those patients, instead of them coming with anxiety knowing that they are going to be getting a needle in their eye, knowing that they might be blurry for a couple of days thereafter might prohibit…grandma from playing in the bridge game the next day. It’s going to be a whole different world for these patients where they now will be coming to the office for safety assessments. I’ll still be monitoring them regularly, but they may not be anticipating the injection. That reduces their anxiety. That improves their quality of life. When they leave my office, they are going to have the same vision as when they came in, so their quality of life is going to be improved for the rest of the day at a minimum if not a few days thereafter. That’s a big advantage. I’m also looking forward to the long-term data with port delivery. We might find that these patients years down the road maintain better visual outcomes than in patients that require injection. For neovascular AMD, it’s going to be wonderful. For the diabetic population, we do not have any data yet but I still anticipate that if it does show efficacy and safety that it will dramatically improve the quality of life of those patients as well. We have talked previously that this is typically the working-class population of patients and they don’t like paying the copays in the office every month for an injection, they don’t like taking the time out of work and they frequently have time where they missed their appointments with me. Instead of them coming back at 1 or 2 months’ interval, they might come back 4 months later. I know when I am giving them an intravitreal bolus of our current standard therapies that that drug wears off, whereas with port delivery, I can rest assure that if that patient is missing my office visit that that patient’s eye is still getting medication and getting treatment that is continuous until I am seeing them again in the follow up. For both populations, I anticipate going to improve their quality.

Carl D. Regillo, MD, FACS: I agree. Like you said, not having to get injections improves their quality of life. They don’t like it, there is no doubt about it. They will put up with it to keep their vision good but I’m super excited about the prospect of better long-term vision outcomes in the real world with true sustained delivery here. We’re already getting the hint of that; we have got that portal extension study which are patients going way back to the phase 2 trial. They have the device and they are getting refilled every 6 months. They have the exact same good vision at the end of 4 years so far that is incomplete––at the end of 4 years they are 20/40 and they started the trial at 20/40. That’s impressive to keep the visual acuity as good as that for 4 years. We don’t have another study out there that is yet to live up to that.

Transcript Edited for Clarity