Macular Degeneration Research

What’s Ahead for AMD—Gene Therapy (September 2021)

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Arshad M. Khanani, MD

The event featured Arshad M. Khanani, MD, who provided an overview of age-related macular degeneration (AMD), including an explanation of how long-acting gene therapy is being developed. There was also discussion about overall vision health and which populations are most susceptible to AMD.


  • BrightFocus Foundation
    What’s Ahead for AMD—Gene Therapy
    September 29, 2021
    1:00 p.m. EST

    Please note: This Chat may have been edited for clarity and brevity.

    MICHAEL BUCKLEY: Hello, I’m Michael Buckley with the BrightFocus Foundation. Welcome to today’s BrightFocus Chat. It’s called, “What’s Ahead for Gene Therapy and AMD.” If this is your first time on a Chat, welcome. I’m going to tell you a little bit about who we are and what we’ll do today. BrightFocus is funding some of the top researchers in world. Those are scientists that are trying to find better treatments and prevention and ultimately cures for macular degeneration and glaucoma and Alzheimer’s.

    Here at BrightFocus, we believe that research equals hope and that science is giving us hope that these very debilitating diseases don’t have to be an inevitable part of aging. And so, with products such as today’s Chat, we try to bring you the latest news from the field of research and give you the opportunity to ask a few questions. We also have a lot of materials on our website, So today, a first-time guest is joining us, Dr. Arshad Khanani. He is joining us today from Nevada, where he’s a retinal specialist, and he also runs clinical trials to try to develop new treatments for AMD. So, with that, Dr. Arshad Khanani, welcome. 

    DR. ARSHAD KHANANI: Thanks, Michael. I’m happy to be here and looking forward to our conversation. 

    MICHAEL BUCKLEY: Would you like to tell us a little bit about your background and, most importantly, why you wanted to go into vision health and research? 

    DR. ARSHAD KHANANI: Absolutely. So, I am a retina specialist, a medical and a surgical medical doctor trained in ophthalmology with a fellowship in retina to really cater to the back of the eye diseases; I also run a big, busy research department here at Sierra Eye Associates in Reno; and I also teach students. I’m an associate professor at the local University of Nevada, Reno, School of Medicine. Interestingly, I got into vision because my grandmother lost one of her eyes after a surgery when I was very little, and I was going to the physicians with her on a daily basis, and I was really intrigued by the tools and technology the ophthalmologist was using, and hence I got into ophthalmology. 

    MICHAEL BUCKLEY: It’s really interesting how an experience like that can shape where you want to go with your career. We asked you to be a part of today’s discussion because we understand you’re working with a company called REGENXBIO on something called RGX-314, which is, you know, a new and exciting possible treatment for AMD. So, I was wondering if you could tell us about gene therapy, about what this approach is and what makes you excited about the progress you’re making. 

    DR. ARSHAD KHANANI: Thanks, Michael. Yeah, it is a really exciting time in our specialty. So, just as a background, for patients with wet macular degeneration, we have multiple FDA-approved treatments, but they’re all injections that are performed in-office in the eye on an every month or every other month basis. So, for wet macular degeneration, we have treatments, but it is a big burden for patients to come in every so often to get their treatments, and they need to continue on that treatment, in most cases, for a really long time. So, RGX-314 by REGENXBIO is a gene therapy treatment. When people hear of gene therapy treatment, they start wondering what it is. The basic concept is that you take a vector that is non-infectious—so, viral vectors that are found on your skin and all over the body that don’t do anything—and you put a genetic code for the drug that you want your eye to produce. So, in this case, it’s a protein that’s similar to an approved medication that is already, you know … people receive in clinics, so you basically deliver that gene therapy to the eye, and then your eye becomes a biofactory and starts producing the protein. So, the goal is that we can essentially have a decreased burden for our patients where you’re producing this protein so you don’t have to get injected. So, in a subset of patients, you can essentially control the disease without getting any more treatment. 

    MICHAEL BUCKLEY: That’s amazing. It really sounds like something science fiction. I think, Dr. Khanani, when a lot of us think about gene therapy, we think about genetics and think about the things that make us who we are—and make us as individuals. Does gene therapy for AMD … does it change someone’s genetic makeup or DNA, or does it sort of help or adjust that? 

    DR. ARSHAD KHANANI: That’s a very good question, Michael. It comes a lot when I’m discussing this with patients. So, this is not changing anything about who you are. This is only about adding a gene for a drug in your cells in the eye so that you don’t have to get that drug injected in the eye. So, the viral vector is injected in the eye, and it goes to the cells of the retina, so it’s not going out into your body or changing anything. It’s just going to the cells in the retina, and now those retinal cells, in addition to producing a lot of different proteins, add this protein, and then this protein controls the disease. So, it is really the treatment of the future. As you know, FDA had approved a gene therapy for another disease a few years ago, so we have an approval on it. So, this is not changing anybody’s genetic makeup. This is not doing anything but adding the gene for the protein that you need to control the disease. 

    MICHAEL BUCKLEY: Thank you. Dr. Khanani, one question that a number of our listeners have already submitted: I believe you mentioned this is currently for wet AMD. Are there other types of macular degeneration where you think gene therapy could be a benefit? 

    DR. ARSHAD KHANANI: Yes, that’s a great question, Michael. So, RGX-314 is looking at patients with wet macular degeneration and also with diabetic retinopathy. Diabetic patients also receive frequent injections to control their disease, so RGX-314 is being looked at in that disease, also. Yes, for dry macular degeneration there’s some early programs that are looking at gene therapy to produce certain proteins so that you can slow down the vision loss from advanced dry macular degeneration. As you know, there’s no current treatment for dry macular degeneration, and we are looking for it, but gene therapy is being looked at, but it’s much earlier stage. The RGX program—the REGENXBIO program—actually, for their wet macular degeneration delivery under the retina is in the pivotal trial, meaning this is the registration trial before it can be approved. So, it is still not approved, it is still in research, but it is ahead of other programs. And in dry AMD we have programs, but they’re very early. 

    MICHAEL BUCKLEY: Dr. Khanani, I was wondering: Our listeners may have heard of stem cell therapy over the years, and I think there’s been some … a little bit of a complicated controversial topic. Is gene therapy the same or different from stem cell therapy? 

    DR. ARSHAD KHANANI: No, no. Gene therapy is totally different. So, you are actually delivering a gene for a protein. So, all proteins that are produced in the body have a code. So, we all have our DNA, and then all of our body cells have codes of genes that produce the protein. So, gene therapy is just putting in the retinal cells in the eye the protein code to produce this protein to control the disease. Stem cells actually are cells that can be derived … you know, attempting to be made to do a function based on the specific organ. And yes, there were some stem cell incidences where in unregistered, non-FDA-controlled settings, people got injections in the eye, and they ended up with a poor outcome. So, this is nothing like that. This is gene therapy, this is totally different, and all the trials that we participate in—all the major companies like REGENXBIO do—are all FDA-controlled trials. So, totally different. I don’t want people to confuse gene therapy to stem cells. 

    MICHAEL BUCKLEY: I appreciate that very strong distinction, Dr. Khanani. And I think that what you mentioned pivots well to talking about clinical trials. And I think because of the COVID vaccines, I think Americans are much more familiar with clinical trials than before a year or two ago. But I think for a lot of us clinical trials are that box at the bottom of the form at the doctor’s office, and you check yes or no, and I think a lot of us … you know, whether you want to participate. So, it seems like something people aren’t particularly familiar with. So, I’m wondering if you could tell us a little bit about how does—in this case with the RGX-314 or others—how does a clinical trial work for AMD? 

    DR. ARSHAD KHANANI: Absolutely. So, I think when people hear the word “trial” they always assume that they’re being a guinea pig and they shouldn’t participate, and you know, we currently have 60-plus clinical trials. So, clinical trials are the only way to get approved treatments for all diseases. And obviously, the FDA has a very robust program where we make sure that patient safety is a priority, and then all the protocols that are written and all the products that are utilized in trials are actually looked at by the FDA before they can be injected into humans. We have long-standing data in nonhuman primates and others before the FDA can allow it. So, essentially, the RGX-314 sub-retinal program actually is now in the pivotal stage, so this is the final stage before FDA will approve it.  

    And in this trial, especially, you are comparing the treatment to standard of care injections in the eye. The FDA will never do a trial for a treatment without a control arm if there’s available treatment. So, before wet macular degeneration treatments are approved, the people had control or sham or placebo, you call it, versus treatment; but now all the trials that are looking at treatments for a disease like wet macular—where we have injections—are looking at comparing the new treatment to the old treatment. And this treatment already has generated over 3 years or so of data of safety and efficacy in the earlier Phase 1B/2 trials. So, when you look at trials, there’s Phase 1, Phase 2, and Phase 3. So, Phase 1 trials, Michael, are the ones where you’re doing first-in-human studies to look at safety and efficacy signal. In Phase 2, you’re doing it in a larger population, and in Phase 3 you’re really doing it to compare it to standard of care. So, you know, RGX-314 has multiple programs, but the sub-retinal program actually is in the pivotal stage. So, for the listeners, I think you need to discuss with your physician what is the right trial for you, and then look at risks and benefits of the trial before you sign up. But I think being educated on why the trial is done and what it’s going to generate is always a good idea. 

    MICHAEL BUCKLEY: That’s really helpful to explain how this works. So, when you talk with your patients or prospective volunteers for a trial, are there common questions or concerns that pop up in a lot of your … a lot of these conversations? 

    DR. ARSHAD KHANANI: Absolutely. The first thing I tell them is that I would never do a trial that I’m not comfortable with injecting this in my mother or my sister or myself. So, I do a lot of homework beforehand to sign up for trials to make sure I’m happy with the safety and efficacy data. And, you know, when I present the trial to the patient, the first question they ask is, “Is it safe?” So, you need to look at the safety of the trial that you are participating, and then the other thing is: How is it going to benefit me or my family members down the road?  

    So, for example, somebody is getting injections in their eye every month for the last 5 years, or let’s say the last 2 or 3 years. And, you know, it’s a drag to come in, get injections, wait in my office for 3 hours, and you know, bring a driver. The family member and a daughter or son or husband or whoever or somebody has to take time off, or the wife can’t do what she’s supposed to do because she has to bring her husband. There’s a lot of burden, so in this case scenario with the RGX program, there’s a good potential that a majority of the patients will just get one and done treatment, so that is very exciting for patients. Of course, when you are in a trial you have to go through some other evaluations to make they’re looking at everything. But the common question is: How is it going to benefit me? And here, we are very busy with this trial because nobody wants to get injections in their eye every month or every other month for the rest of their lives, so having that opportunity of a one and done treatment is very promising. 

    MICHAEL BUCKLEY: This could really be a real game-changer for treating wet AMD. So, several of our listeners have submitted questions about, essentially: Are you still recruiting for this trial, and how would someone get either into this particular trial or a similar trial related to wet AMD? 

    DR. ARSHAD KHANANI: Yeah, so the best thing to always do is to ask your physician about the ongoing trials and see if you are a good fit for it. If your physician doesn’t do the trial, they’ll probably know somebody in the area who’s participating. So, yes. The RGX-314 REGENXBIO program—the sub-retinal program for wet macular—is currently recruiting, and the way to find out is you can also go to—that’s the website—and you can just put RGX-314 or wet macular degeneration, and this is a government website that shows you about all the ongoing trials. They also have ongoing trials for diabetic retinopathy with in-office delivery, and also another in-office trial for wet macular. So, I think the best way is to speak to your doctor, figure out if you’re a right fit, ask them to see if they … in the area who is doing it, and then that’s a great way to get to know. And remember, there’s a lot of inclusion and exclusion criteria for each trial, so not every patient qualifies for every trial, but the only way to find that out is to speak to your doctor or the site that is doing the trial. 

    MICHAEL BUCKLEY: Dr. Khanani, what’s the timeline, do you think, for this study that you’re helping run? Like, where do you think timeline-wise things go from here? 

    DR. ARSHAD KHANANI: Well, so, as I mentioned, there are several different programs with RGX-314. The pivotal program that’s currently recruiting is the first of the two pivotal trials. So, usually, you know, you’re looking at several hundred patients, and it takes a few years to recruit, and then you get the data in a year or two after that. So, we’re looking at within the next 3–5 years we should know about the data from the pivotal trials. And when I say “pivotal trials,” it means that if the trial data is positive in terms of efficacy and safety, that FDA application gets filed by the company, and then that treatment is available for patients. So, yes, gene therapy is ongoing work. REGENXBIO’s programs are very advanced, but again, they’re still in clinical trials, and they’re not approved for general population yet. We are hoping, within the next 3–5 years, that we may have an FDA-approved medication if the trials show the efficacy and safety that we are looking for. 

    MICHAEL BUCKLEY: I just have a couple of clarifying questions that we received from listeners. If this is successful, do you see it as a one-time lifetime treatment, or is this something that would need some sort of boosters over time? 

    DR. ARSHAD KHANANI: So, that is a very interesting question, because when you look at wet macular degeneration, Michael, it’s a very heterogenous disease—I call it—meaning there are patients who need injections every month to control the disease, and there are patients who only need injections every 2–3 months. So, we have some new treatments coming out that may benefit patients that go maybe 3–4 months, but basically the need of each patient is different. So, what we have seen is that, in the earlier Phase 1B/2A trial—earlier-stage trial—I would say about two-thirds of the patients were injection-free after getting single treatment with RGX-314. So, this is going to be a one-time treatment; this is not going to be a repeated treatment because the goal is to, you know, make your eye a biofactory to secrete the protein. So, this is a one-time treatment. And there’s going to be a subset of patients who may need regular injections in between if their disease is not super well-controlled, but even if it’s a patient that is getting an injection every month, and now you get this treatment and you only need an injection every 4 or 5 or 6 months, I think that still is a game-changer in terms of controlling the disease. So, a majority of the patients will be … I mean, all of the patients will receive one-time treatment. For a majority of the patients, the hope is that they’re going to be treatment-free after getting this. 

    MICHAEL BUCKLEY: One of our listeners is wondering … a sort of process question. If something’s approved by the FDA, does that mean that Medicare and Medicaid and insurance would cover it, or are those two separate decision tracks?  

    DR. ARSHAD KHANANI: It is like a … it’s like a step-wise procedure. So, once you have the data available and it’s positive, then there’s a package that the companies file with the FDA for approval, then FDA takes their time—whether it’s 3 months or 6 months or a year. Based on what they provide, they approve the drug. After the approval is obtained, then that drug goes to Medicare and insurance companies, and then they come up with a code for it so that it can be billed. Obviously, you know, after FDA approval comes the availability from insurance companies and Medicare, and Medicare is usually the first one to approve it. So, the hope is that once the FDA approves the drug, there’s only a few months or a short gap before it’s available for patients, based on what the company decides when to launch the product after the approval.  

    MICHAEL BUCKLEY: I appreciate that clarification. We have a listener wondering about gene therapy—like what you’re working on and others. Would this help people that are currently receiving no benefit from injections, or is this aimed at improving the treatment for people when the injections are working? 

    DR. ARSHAD KHANANI: So, for wet macular degeneration, Michael, I would say 95-plus percent of patients actually respond very well. The question is visual acuity, and we are getting vision or stabilizing vision, and that all depends on how the patients present. If they present with a big hemorrhage or a scar, then it’s very difficult to reverse that, but we maintain whatever they have, whereas if they come with fluid, they can see better. So, this treatment will be for patients who are responsive to the current standard of care injections because it is a protein that’s very similar to the one we inject in the eye. So, in the trials, actually, you have to show a response to the injection before they can be considered for the gene therapy because, obviously, we want to give it to people who are get the most benefit out of it. 

    MICHAEL BUCKLEY: It makes perfect sense. This is a really exciting overview of your research. Are there other projects in vision research on AMD that you’re very hopeful about? 

    DR. ARSHAD KHANANI: Yes. I think the gene therapy is going to be a game-changer, as you and I called it, and I think it really will be. We have certain treatments that are very close to FDA approval. We have a molecule that we inject in the eye called faricimab that showed positive Phase 3 data, and that molecule can last longer than current molecule, so you can have less injections. Once it’s approved … it is with the FDA. The decision will be happening in the next few months, we are hoping.  

    There is another treatment called the port delivery system. It’s a surgical port that’s laid in the eye, and it releases the drug that they inject in-clinic. So, instead of getting injections, you get the port surgically and then you fill the port in-clinic every 6 months, so you don’t have to come in for injections frequently. That is with the FDA—also has shown comparable data to monthly injections—and we should hear from FDA about it in a month or so whether they approve it.  

    And then, there’s a host of other things that are happening, Michael. I won’t get into it, but all I want to tell to the listeners is that this is a really exciting time for everybody suffering from retinal diseases. We are doing our best to make your lives better, and we all need to work together and partner together so we can come up with better treatments, and there’s hope and light at the end of the tunnel here to make sure that we keep our precious sight for all of our patients.  

    MICHAEL BUCKLEY: A couple of listeners have asked if this gene therapy would help Best disease—B-E-S-T. Is there any connection between the work you and others are doing and Best disease? 

    DR. ARSHAD KHANANI: So, this treatment is—that we talked about—is for wet macular degeneration. Best disease is a macular disease, but it’s a genetic disease. So, there’s a lot of different companies that are looking at rare disease, and they’re targeting gene therapy for it. I’m not part of any trials with the Best disease, but if the listener wants to go on and put “Best disease,” they should be able to see if there’s any programs around the country that are looking at treatments or looking for patients for Best disease. 

    MICHAEL BUCKLEY: Thank you. In the few minutes that we have left together, I was wondering if you could kind of go “big picture” for a couple of minutes. In your experience as a retinal specialist and in health care, is there a main piece of advice you wish all your patients knew, or is there a common guidance that you try to make sure that families that are impacted by AMD are aware of? Is there something that you’d like all of us to know and to take to heart? 

    DR. ARSHAD KHANANI: Absolutely. I think the most important thing for anybody is to make sure that they take care of their eye health. That means seeing an ophthalmologist on an annual basis to make sure that there’s no pathology. When I say ophthalmologist, also optometrists are great, so please see your eye doctor, in general, on a routine basis. And if you have somebody with macular degeneration in your family, it’s a good idea to get checked for it. You can see a retina specialist, if you can get into one, just to get a baseline exam. And then, any vision changes you have that are acute, please get into your eye doctor’s office sooner than later. I can’t tell you how many times I have patients who come in too late with their macular degeneration or other diseases, and you wish that, if they came early, you could have actually saved their vision more. So, the bottom line is, please, see your eye doctor. Please make sure that your eye health is taken seriously, and if you have any new symptoms, please contact your doctor so you can get an evaluation. The earlier you treat a disease, when it comes to retina, the better outcome you’re going to have.  

    And then, the other last advice is that, if you have macular degeneration and you’re getting treatments—injections—every month or every other month, you know, after initial three or six injections, once the disease is controlled, you may not see a benefit, and a lot of patients want to drop off treatment thinking that the treatments are not working. The treatments are actually to maintain the vision, so please do not drop off your treatment plan that’s given by your doctor. Please make sure that you follow the treatment plan and stay on course with treatment as recommended by your doctor. 

    MICHAEL BUCKLEY: That’s certainly great advice, Dr. Khanani, and I know somebody that we work with at BrightFocus uses the expression “a check-up from the neck up,” which I think always drives home that point that you mentioned of really taking care of your vision health, and I think it’s something, like you said, a lot of people take for granted until a problem happens.  

    One other big picture question: With your patients, do you see harm or benefit from lifestyles, such as diet, exercise, smoking, sunglasses, wearing a hat? What type of advice or best practices do you try to impart to your patients on those lines? 

    DR. ARSHAD KHANANI: Yes, absolutely. You know, a healthy diet is super important for your vision health. Green, leafy vegetables, more on the Mediterranean diet routine, is good. A diet in good … you know, high in vitamins and also omega-3s is good. And I also recommend everybody to wear sunglasses outside. I personally do that, and so I think a healthy lifestyle with good eating and exercise is important for your eye health. And a lot of times a question comes about vitamins and what vitamins and eye vitamins and vitamins for macular degeneration. I think those things you have to discuss with your doctor. Based on the status of your eye health, they will recommend something. So, it’s one of those things where not everything helps everybody, so we need to make sure that any treatment you take or any vitamins you take, you discuss with your doctors. But a general guidance is to eat healthy green, leafy vegetables; sunglasses; and exercise if you can. 

    MICHAEL BUCKLEY: That sounds like great advice for all of us. Our next Chat will be on Wednesday, October 27—just a little under a month, October 27. It’s going to be very similar to today. We’re going to get another update on clinical trials. This one, we’ll be hearing what’s the latest research about slowing and stopping vision loss from geographic atrophy—the form of dry AMD. So again, that’s October 27 we’ll be back.  

    Dr. Khanani, I just want to thank you so much. It’s been really exciting to hear your work. It seems like something back in the day would have been out of a science fiction movie or science fiction novel, so it’s tremendously exciting that we got to hear about this first-hand. Any kind of concluding thoughts or comments that you’d like to leave the listeners with, Dr. Khanani? 

    DR. ARSHAD KHANANI: Well, first I want to thank you and the BrightFocus team for having me here, and I want to thank the listeners for spending their time to join us today. I think the bottom line is that it is a very exciting time, as I’ve said, and I’m very honored and humbled to be part of this innovation that’s happening in our field of retinal diseases. And gene therapy clearly is going to be a game-changer for our patients. And our hope is that all of us working together—patients, physicians, and companies—will come up with treatments to help our patients. So, I just want our patients to stay hopeful that there is better treatment coming out down the line, and to take care of their eye health now, and to stay on their treatment course until new treatments are available. And personally, I’m super excited to be a part of gene therapy, and it appears that it is real now. We have talked about it for decades, but the time is now, and hopefully, in the next few years, we have a treatment option for our patients. So, thanks again, Michael. 

    MICHAEL BUCKLEY: I really enjoyed this conversation, and I think you’ve given our listeners a lot of really encouraging updates and kind of a very specific sense of the progress that’s being made in vision science, so I think we’re moving in the right direction.  

    To our audience, thank you very much for being a part of today’s BrightFocus Chat. We will be back on October 27 to hear the latest research about geographic atrophy. On behalf of Dr. Khanani and everyone here at BrightFocus, thank you very much for being a part of today’s conversation. Thanks. 

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