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Please note: This Chat has been edited for clarity and brevity.
MICHAEL BUCKLEY: Hello, I’m Michael Buckley with the BrightFocus Foundation. Welcome to today’s BrightFocus Chat: “Clinical Trial Update: News on Wet AMD.” If this is your first time on a BrightFocus Chat, welcome. I’m going to tell you a little bit about BrightFocus and what we’ll do today on the Chat.
BrightFocus Foundation funds some of the top researchers in the world. These are scientists who are trying to find cures for macular degeneration, glaucoma, and Alzheimer’s. We share the latest news from these scientists with families that are impacted by these diseases. We have a number of free publications and plenty of materials on our website, www.BrightFocus.org, that offer tips for living with these diseases, such as macular degeneration. Today’s BrightFocus Chat is another way of sharing this information.
Our guest speaker is Dr. Christopher Brittain. He’s the Interim Global Head of Ophthalmology and Clinical Development at Genentech. Dr. Brittain will give us an update on an AMD clinical trial that his company, Genentech, is currently running.
Before we turn to Dr. Brittain, let me tell you a little bit about BrightFocus’ role in today’s topic. BrightFocus Foundation partners with Genentech and many other leaders worldwide on macular degeneration. Our job today is to share with you the latest news on AMD.
It’s important to know that BrightFocus does not endorse any specific medication or medical procedure. Our role is very simple: It’s to keep you as informed as we can, and from there it is up to you and your doctor to decide what is best. So without further ado, let’s welcome Dr. Cristopher Brittain to today’s BrightFocus Chat.
DR. CHRISTOPER BRITTAIN: Thank you, Michael, and thank you very much, indeed, for the kind invitation to share some information with the people on the line. It’s a great opportunity, and I really appreciate it.
MICHAEL BUCKLEY: Great, thanks. Could you tell us a little bit about what you do, your background, and what you’re currently doing at Genentech?
DR. CHRISTOPER BRITTAIN: Sure. I’ll start by just briefly summarizing who I am. You can probably hear from my accent that I’m a British-trained physician by background. I completed my ophthalmology training as an eye doctor in the U.K. Since then, I’ve worked in clinical practice in the U.K., with our healthcare regulator in the U.K., and then into industry where I also spent a couple of years in the U.K. working. I then moved the family out to Switzerland, also, for a couple of years. Then I moved my family once more 2 years ago to South San Francisco. At the moment, I’m—as you said—the Interim Global Head of Development for Ophthalmology, which means that I lead a large and exciting team to research new medicines in ophthalmology and to bring those medicines as quickly and effectively and efficiently to patients as we possibly can.
MICHAEL BUCKLEY: Well, that’s great. That’s quite an impressive background. Dr. Brittain, we invited you today to represent Genentech because we understand you’ve got some positive news about a new potential treatment for AMD. I was wondering if you could tell us a little bit about this port delivery system and how it works.
DR. CHRISTOPER BRITTAIN: Sure. I’m very happy to. What we call the port delivery system with ranibizumab, we’ve abbreviated to PDS for ease. This is a super-exciting program for us. In simple terms, this is a small implant, which is about the size of a grain of rice, and it’s implanted underneath the upper eyelid, which means that it’s not visible to the person who has it implanted, to their family, who they talk with, and it does not interrupt their field of vision.
What the implant does is that it’s got a very small reservoir where we can fill it up with medicine—in this case ranibizumab, commonly known as Lucentis®—and the device continuously releases the ranibizumab over an extended period of time into the eye. And the intention of the device is therefore to reduce the number of hospital visits that people have to undertake who have wet age-related macular degeneration, while at the same time giving the outcomes which we expect from these gold standards of care, which is anti-VEGF treatment, being Lucentis® or other treatments available.
The study results to date have been super exciting. We’ve had one Phase II study, which we call the LADDER Study. The Phase II study really looks at: is the device safe enough to do a large study in, and is it effective enough? Does it do what we want it to do in terms of treating the wet AMD effectively enough? And it certainly does, and the top-line results were that 80 percent of people could go 6 months before requiring a refill of the PDS implant, so this is really a ground-breaking opportunity to really address the treatment burden.
MICHAEL BUCKLEY: Well, that’s exciting news. Just to make sure I heard the number, did you say 80 percent?
DR. CHRISTOPER BRITTAIN: Yeah, absolutely. That’s 80 percent of people went at least 6 months without requiring a refill of the device.
MICHAEL BUCKLEY: That’s really exciting. I was wondering if we could kind of start at the beginning of that process. How does this implant get implanted?
DR. CHRISTOPER BRITTAIN: Again, great question. The implant, as I said, is about the size of a grain of rice, so it’s very small. The implantation procedure is done in a day case or operation theater, so you have to have surgery. The surgery takes less than 45 minutes, so a little bit longer than a cataract procedure, but not much longer in terms of the amount of time taken. It’s implanted into the eye, so it can release drugs continuously into the eye, and people who have it implanted can go home the same day. So, while it’s a complicated procedure, it’s relatively simple in terms of expectations and burdens for people having the operation.
MICHAEL BUCKLEY: Great. And how long does that implant stay in a person’s eye?
DR. CHRISTOPER BRITTAIN: Currently, the plan is this is in fact a permanent implant, so it will be in there for as long as the patient needs it. The goal is that it can be continuously refilled, so it doesn’t just sit there; it continuously delivers effective treatment.
MICHAEL BUCKLEY: And, Dr. Brittain, how does it get refilled?
DR. CHRISTOPER BRITTAIN: Again, this is a very exciting method whereby it’s super simple: topical anesthetic eye drops in the physician’s office—a very routine procedure—and takes under 5 minutes, really, to do. It’s very similar to the current intravitreal injections which people currently have.
MICHAEL BUCKLEY: How often does that get refilled?
DR. CHRISTOPER BRITTAIN: So, as I said, within the earlier study which we formed, which was called the LADDER Study, 80 percent of people went for at least 6 months before requiring the refill, and many went much longer. However, what we’re doing in our subsequent studies, really looking to make sure that the most patients benefit from the treatment as possible, and therefore we’re investigating how patients fare with refills every 6 months, so that’s the goal: 6-month refills.
MICHAEL BUCKLEY: And so that 6-month refill, is that kind of in lieu of a current every-4-week frequency? I’m trying to sort of compare what you’re testing versus the current practice.
DR. CHRISTOPER BRITTAIN: Sure. The current practice kind of varies somewhat among different treating physicians, but the current standard of care for most anti-VEGF therapies is either monthly follow-up and injections or kind of a treat-and-extend approach, whereby injections are up to every 6 weeks or even up to every 8 weeks. But certainly, with 6-month refills, the intention is to really eliminate as many of these visits as possible for the patient’s sake.
MICHAEL BUCKLEY: Wow. That could really make a big difference in people’s lives. So potentially, twice a year instead of maybe 12 times a year. During that 6 months, do you have a sense of how frequently patients should see their eye doctor during the time that is currently filled up?
DR. CHRISTOPER BRITTAIN: I think currently the status of the PDS is that we’re in the clinical trial period. So, within the clinical trial, people are being seen every month just to make sure that we capture enough evidence to demonstrate that it’s safe and effective and does what it says it does. How it’s managed once it becomes available, and if it’s available on the market to patients in a number of years’ time, the goal would clearly be to just have a 6-month refill, so just be seen every 6 months.
MICHAEL BUCKLEY: Well, that’s fantastic. Is the refill processed similar to how it is filled at the beginning?
DR. CHRISTOPER BRITTAIN: It’s slightly different. When the device is first implanted during the surgery, the device is already filled just prior to being put into the eye. During subsequent refills then, as I say, there’s the local anesthetic eye drop which is put on the eye, and then it’s refilled in the physician’s treating office. So it’s much, much smoother on the refills.
MICHAEL BUCKLEY: Well, that’s good to know. It strikes me that there’s a potential for greater adherence, greater compliance, if people don’t need to get those monthly treatments. Do you see an opportunity for more consistency?
DR. CHRISTOPER BRITTAIN: I do. I do. I think one of the challenges with the currently available treatments is that people do have to go in very regularly, and if you do miss an appointment for any number of reasons—being it weather, unavailability of a partner or friend—then people are losing vision, and we see this with studies looking at patient outcomes with current treatment methods. And the goal, therefore—if we reduce that treatment burden, then I think the ability to really improve outcomes potentially is very, very significant, and I think it’ll be the intention, clearly, that it’s a great opportunity. And it will be exciting to see what the Phase III clinical trial program comes out with in terms of outcomes.
MICHAEL BUCKLEY: That’s great. Dr. Brittain, you mentioned that you went through a Phase II trial, and you explained what that is. I understand what’s next is a Phase III. Can you tell us a little bit about what differs a Phase III trial from Phase II?
DR. CHRISTOPER BRITTAIN: Sure, that’s a really important question. A Phase II study is about establishing that a product or a medicine—in this case a device with a medicine in it—is safe and has a suggestion that it works well, and the results from our Phase II were very strong, so it’s very clear that it does work.
The Phase III trial is the study that provides the evidence for a much larger number of patients, and it helps, first of all, to really enforce the level of safety of the product for the medicine. But secondly, and more importantly, it really establishes the exact level of effectiveness, how well the product works. The Phase III study is about double the size of the Phase II study, so many more people are involved, and we’ve become very confident after a Phase III study as to whether or not the product works effectively. So, we’re in the Phase III study at the moment, as you said.
MICHAEL BUCKLEY: That’s great. And in Phase II, how many people participated in the study?
DR. CHRISTOPER BRITTAIN: There was a total of 220 patients for the Phase II study, and the goal is, for the Phase III program, about 360.
MICHAEL BUCKLEY: Great. When you talk about how you’re looking to test the effectiveness of a new idea, what type of safety concerns or sort of challenges are you looking for during these phases of the clinical trial of the PDS?
DR. CHRISTOPER BRITTAIN: Sure. I think, as we all know, the established safety profile of the current standard of care is exceptionally good. Ranibizumab—Lucentis®—has been around since 2006. Other available [treatments] like Eylea® have been around for a number of years, as well. We know the safety profile is very good with the actual medicine itself. Therefore, the main focus of the Phase III trial in terms of the safety is really just to make sure that the surgical procedure works well, so we’re incredibly focused as an organization on training our investigators in the exact technique to perform the implant and to make sure the implant remains in the eye in a safe manner and doesn’t cause an issue. And we’re excited that the safety profile of the device was great in the Phase II study, and we’re hoping to continue to improve on that in the Phase III study.
MICHAEL BUCKLEY: BrightFocus will have information here for how people can learn more about this trial and possibly enroll. But I was wondering if, Dr. Brittain, you could tell us a little bit about some of those questions. How would people proceed if this was something they wanted to learn more about and possibly enroll in?
DR. CHRISTOPER BRITTAIN: Sure. Thanks, Michael. This is an actively recruiting Phase III study, which means that we are really looking for people who are interested in participating, so many thanks for raising the question. So, people who are interested, we have a number of ways. First of all, you can find out the trial sites at www.ClinicalTrials.gov, and I believe we’ll make some more information available at the end of this discussion. Another way is to ask your treating eye doctor about participation in such a study, and he or she can reach out to www.ClinicalTrials.gov or directly to Genentech. This is a great opportunity, and we have trial sites all over the U.S., so we would hope that this would be available as an option to most people. Obviously, it depends on the stage of your disease, as we do have what we call inclusion and exclusion criteria, which means that not everybody would be suitable for the study. But even if you’re not suitable there may well be other studies for which you are suitable.
MICHAEL BUCKLEY: What would some of those inclusion and exclusion guidelines be? What type of person are you looking for?
DR. CHRISTOPER BRITTAIN: Well, first of all, the most important thing is that these are long studies—this is a 2-year study—so we really want someone who is committed to coming in every month for the full 2 years. If we have people who aren’t able to commit to that, then it can be quite detrimental and quite harmful to the success potential for the study. So that’s probably the most important one: Can you fully commit? And we make it as easy as possible for that, and the company will provide transport, etc.
Outside of that, we look for patients who’ve been treated or are currently untreated, so if you have any new disease in that eye. And there are a number of other characteristics outside of that, but I think number one is probably the motivation and desire to kind of spend what is a fair amount of time on the clinical trial.
MICHAEL BUCKLEY: What do you think motivates the participants in your trials?
DR. CHRISTOPER BRITTAIN: At the end of studies we often get lots of feedback from people, and their main motivation is consistently, “We really want to do this for our family who may get this disease in the future.” So, I think it’s sort of the contribution to science is a lot of what this is about. I think this particular study, what we’ve heard anecdotally—is that the device…they do seem to like it. And they want it in their second eye, which also has wet AMD. The idea that it’s only refilled every 6 months just really kind of eliminates that need for these regular monitoring visits and regular intravitreal injections.
MICHAEL BUCKLEY: You said it’s available in trial sites all across the U.S. How do you and your company, Genentech, pick the locations and train the physicians? How does it go from Genentech headquarters to places throughout the U.S.?
DR. CHRISTOPER BRITTAIN: Again, that’s a great question. As a company we’ve been working in ophthalmology, and specifically the retina—the back of the eye—disease area, since about 2006 and earlier. Since that time we’ve done many, many clinical trials. We’ve had many thousands of people in the community to give their time as patients to these studies, so we know the trial sites very, very well.
The way that we select trial sites is, first of all, have they got a good history of recruiting people into the studies effectively and efficiently over a number of years? Secondly, we need a good geographic spread. We don’t want to take everybody from one single city, so we need to make sure that people have the opportunity all over the U.S. to participate in our clinical trials, and that’s really important to us because it leads to the third factor, which is diversity. I think this is really important. We don’t want to focus on just an affluent area or just a specific ethnic mix in a certain area. We want to have [study groups] as diverse and as inclusive as possible in our clinical trials. Those are the three areas that we find to be important.
MICHAEL BUCKLEY: That’s interesting. It seems that it allows people to, in many cases, continue the relationship they have with their physician while also doing what you describe as something just very, very admirable to help advance the field of science and help family members.
So, Dr. Brittain, as people contact your company or contact BrightFocus for more information, what is the exact name of the study we’re talking about today, so people can begin pursuing more information?
DR. CHRISTOPER BRITTAIN: Sure, that’s one thing I haven’t mentioned yet. The Phase III is called Archway. We have an extension study, but the recruiting study is currently Archway.
MICHAEL BUCKLEY: Great. So, as people begin talking with your company or their physician, it’s Archway—like going through an arch—or Port Delivery System… So, that’s good to know. Dr. Brittain, in the time we have left, are there other things you think people should know about this study? Or common questions or concerns that people might have? For example, you said it’s the port delivery system. That’s the vehicle that folks have. Is that what they should ask for?
DR. CHRISTOPER BRITTAIN: Yes, that’s right. The first thing…the first one I’d make is, even if people are in half a mind as to whether or not to participate in this study, please do feel free to reach out to your physician and to BrightFocus and ask for more details. We are actively recruiting. And I think that this is the only implant in Phase III. We offered such an extended treatment duration, so I think it’s an exciting trial to be in if you have a choice of clinical trials. I think those are the two things. I just encourage and thank you for even considering participation.
MICHAEL BUCKLEY: And if all goes well, what’s the timeline for a trial like this at some point becoming a common practice? What is the best-case scenario over time here?
DR. CHRISTOPER BRITTAIN: As I say, this particular study is about 360 people, and that can take, you know, a year, up to a year and a quarter, maybe a year and a half to recruit. So, if we say an upside of a year—so we complete recruitment by the end of next year—then we need to wait another 10 months or 12 months to get the results, and after that we have to take it to the regulators, and that can take up to another year. So, we’re a number of years off. Saying that, my experience is that those years go very, very quickly, so when it does come and if it’s successful, it will be here very, very fast.
MICHAEL BUCKLEY: In terms of the regulators, is that the FDA? The Food and Drug Administration?
DR. CHRISTOPER BRITTAIN: Yes, absolutely right. Yes.
MICHAEL BUCKLEY: And what do they look for when they’re looking at the trials that you run?
DR. CHRISTOPER BRITTAIN: They look for a number of factors. Number one is that there is an appropriate balance of efficacy, as in, does the drug work? Does the medicine and the device work? Again, safety. Within eye care, particularly with wet AMD, we know that the standard of care, which is intravitreal anti-VEGF injections, they have a very strong safety and effectiveness and efficacy so far. Therefore, the FDA will be looking at how safe is this additional element (i.e., the surgical procedure), and how well do patients do with the device in the eye as a permanent implant compared to the monthly intravitreal injections? So really, they focus on the balance of safety and benefit.
MICHAEL BUCKLEY: If someone is getting injections currently but they’re not working well, is that a person who could participate, or does somebody need to be successfully getting these injections right now?
DR. CHRISTOPER BRITTAIN: That’s a good question. Currently, the inclusion criteria…I’ll give you just a couple. It can be in either eye, number one, but not both eyes. Number two, the person has to have been diagnosed within 9 months in the study eye. And number three, we want to have demonstrated that an anti-VEGF treatment has been shown to be beneficial to the patient within that time period. So, I think if an anti-VEGF injection is having absolutely no effect, then that probably would not be appropriate in that eye, but then maybe the other eye is benefitting if the other eye does have wet AMD. So, I think it would still be worth having a discussion. But we don’t want a patient to have an implant with an anti-VEGF drug, like ranibizumab in this case, when we know that anti-VEGF does not work in that person.
MICHAEL BUCKLEY: That’s very helpful. Dr. Brittain, on behalf of BrightFocus, I just want to say thank you for being so generous with your time. I think you’ve passed on very interesting and promising information to our audience, and the next step is for them to talk to their physicians. But we’d love to keep in touch with you as the trial goes on, in case there are more updates or anything else you’d like to share.
DR. CHRISTOPER BRITTAIN: Thank you, Michael, and I thank everybody for calling in and listening. I’m very pleased to be involved and I’d love to come back and then provide updates as necessary.
MICHAEL BUCKLEY: Great. Thank you, Dr. Brittain.
