Extended Durability of Anti-VEGF Therapies Remain an Important Next Step in AMD Treatment
Nimesh Patel, MD:
Hi, I’m Nimesh Patel. I’m from Mass Eye and Ear Boston Children’s Hospital. I’m an adult and pediatric retina specialist there, and part of the Harvard Medical System.
Interviewer:
What are the challenges surrounding adherence to treatments in AMD?
Nimesh Patel, MD:
There are some significant barriers to treatment in AMD and one of them is just coming into the office. A lot of the treatments we have require monthly or even every other month dosing, and a lot of our patients at this stage of life with age-related macular degeneration may be older and have less access to transportation. They may not be driving. More than that, they also have vision limiting problems and other comorbidities. Patients of this age also have many other appointments they have to get to. Really, it’s coming into the office, is one of the biggest barriers to care for these patients.
Interviewer:
How does lack of adherence impact outcomes?
Nimesh Patel, MD:
That’s interesting. Sometimes it surprisingly doesn’t. There’s been a couple of times where I’ve had patients miss appointments for six months. They went into the hospital and they come back and their macular degeneration wet AMD looks exactly the same. And it probably means that in some cases we are over-treating. With that said, there are some cases where patients can miss two or three injections, get a subretinal hemorrhage that leads to fibrosis and scarring and permanent vision loss. It can go either way. Sometimes they don’t really have much of a problem with missing treatments, and then it can go completely opposite where they scar and they really can’t recover the vision, so it can then cause a negative impact in some cases.
Interviewer:
What are the currently available dosing schedules for anti-VEGF therapies?
Nimesh Patel, MD:
They’re pretty variable. Initially a lot of the medications were approved for eight week dosing, and since added labels for Q4 week dosing, and that’s really become pretty much the standard at this point for dosing schedules that they can be dosed up to a month or longer. Some other medications that have recently been improved are saying that they can do longer dosing, but you can still dose Q4 weeks if you like.
Interviewer:
What treatments are currently being studied to evaluate longer durations of action?
Nimesh Patel, MD:
It’s an exciting time in retina. There’s quite a lot of new medications in the pipeline. Some of them are in the same class as Anti-VEGF which are some of the treatments that we have and some are modifications of that, so in some, there’s a KSI-301 which is in theory potentially supposed to last longer, that’s still in clinical trials, that’s still yet to have a definitive result. Additionally, Aflibercept is making a higher dose Aflibercept. There’s also different classes of medications in general, including tyrosine kinase inhibitors with sustained release delivery platforms that are being looked at. But there are many companies and types of deliveries that are being studied to try to extend the dosing to help that problem that we’ve had with patients coming in.
Interviewer:
Can you explain “variable frequency anti-VEGF treatment” and “treat-and-extend” regimens?
Nimesh Patel, MD:
Yeah, so there’s a few different types of treatment methods that doctors use. The first one is probably just sustained dosing every month. That has shown in some studies to really be the most effective, and that when we treat-and-extend, sometimes the visual gains are not as good. However, as we talked about, monthly dosing is a real big barrier for patients, so we try to limit the amount of injections and do treat-and-extend.
Treat-and-extend means treating, and on the next exam, spacing it out a little bit further, even if the retina is flat, still doing an injection at that time, and then spacing out the next injection even further. Then, if they get worsening of disease or worsening fluid, you may bring the dosing interval down again. Now, variable dosing or potentially as needed dosing could be that you have pre-specified criteria that you’re using either occurrence of fluid or drop in vision or hemorrhage, and you’ll really only inject for one of those criteria or at a maximum of potentially 16 weeks. Those are the different types. I think most people are on a treat-and-extend protocol, but I think any of the options are generally considered fine.
Interviewer:
What current and future platforms may be used to extend delivery? (i.e., Port Delivery System, implant, gene therapy)
Nimesh Patel, MD:
Yeah, the one that’s probably the most close to primetime at this point is the Port Delivery System. That has been FDA approved and was studied in clinical trials and showed that in a large majority of patients you could do Q6 month refills after a surgical procedure to implant the device. The downside of this, there were some complications with conjunctival erosions in the clinical studies, although they were very rare. Since that device has been recalled because of some concerns about the refilling procedure and the device itself. That’s one of the main things that we’ve been looking at.
Other things that have been looked at is gene therapy. There’s companies looking at gene therapy in terms of a intravitreal or subretinal approach. What that does is it allows the eye to actually produce the medicine by altering the DNA, and that’s something that could potentially at least decrease injections or eliminate them altogether. These are still in the early phases of clinical trials and really haven’t quite shown that they’re as effective as what we currently have at this point.
