Trajectory of the Changing GA Treatment Landscape


In their final thoughts, the panelists explore the future of GA treatment strategies.

Ryan Haumschild, PharmD, MS, MBA: Now I would like to really transition into the future considerations of geographic atrophy [GA]. Obviously, there’s been a lot of excitement here recently around complement inhibitors, and I feel like the treatment of the future landscape is even more exciting. And we’re going to have more options for our patients to really improve outcomes, give durable responses, and ultimately, improve the quality of life. Dr Lally, I would like to start with you. What are you most excited about in the treatment landscape of GA in the next 5 years? And what are some final thoughts that you want to share with our viewing audience from today’s discussion?

David Lally, MD: I think the take-home message that I’m excited about is there has really been an explosion of clinical trials and different strategies of trying to tackle this disease of GA. Blocking complement is one very important part of the puzzle. But as we have seen and we have talked about earlier, complement inhibition is really just the tip and just the start of what is to come. And really our goal is we want to prevent GA from even developing, or if it develops, we want to stop it in its track. These new therapies are really the first step of showing a slowing progression, but the disease is still progressing. We do not want it to progress. We want to stop it or prevent it from even developing. There are a lot of different strategies out there beyond complement [inhibitors] looking to try to accomplish this goal. Something we look at is neuroprotection, which is a big umbrella term that’s kind of even hard to define what neuroprotection means. But I think neuroprotective medicines that can protect the retina; the retina is like an outpouching of the brain. We consider it like neural tissue, an outpouching of the brain. Any medication that can really preserve neuronal health, I think is going to be an exciting place to look. I think what is exciting is there is a lot of work going into trying to design and figure out end points that can be used to see the effects of treatments at the intermediate stage of dry AMD [age-related macular degeneration] before GA develops. And I think, again, if we can find really good clinical trial outcome measures, for the development of GA, in a reasonable time frame to run a clinical trial, I think we are really going to see the field move forward. There are a lot of people working on functional outcome measures, on structural outcome measures, to really try to help us hone in there. I think regenerative medicine is interesting. Some strategies are looking at replenishing the atrophic area with pluripotent embryonic stem cells. And there’s some work that is actually getting into the later stages of development. Stem cells, although we are not all the way there yet, I think are starting to make some progress in the development of hopefully getting to an FDA-approval someday, and actually restoring the loss of the photoreceptors. But to me, the most encouraging if we look at these complement inhibitors is I hope someday we have gene therapy for these complement inhibitors. Wouldn’t it be wonderful if we could give one intravitreal injection with a gene therapy that went into the cells, and we had our own retina cells make the complement inhibitors themselves where it went on forever? Because, as I mentioned earlier, these patients live with this disease for the rest of their lives. The way it’s looking right now, in the current state, they are going to be receiving intravitreal injections, either monthly or every other month, indefinitely. I think gene therapy is a place to be watching in the future. But the take-home message is it’s a really exciting time if you are a patient with GA. This is really a hallmark time in our field, having our first FDA-approved treatment. Hopefully, we may have a second soon in the summertime. The knowledge is really exponentially moving forward, and I really think in 5 years we are going to have even a lot more knowledge and we are going to have a lot better treatments coming for our patients.

Ryan Haumschild, PharmD, MS, MBA: Absolutely. Great final comments. And a lot more real-world evidence to make more informed decisions. Dr Lopes, curious what are your thoughts on how you expect the treatment landscape to change in the next 5 years, and upon that, what are your final thoughts from today’s discussion?

Maria Lopes, MD, MS: It’s certainly an exciting time to be in this disease space and going from no treatments to several, with 1 already approved and more in the pipeline. I guess until there is a cure, there is an unmet need. Exciting to see not just slowing disease progression, but that we’re looking at different mechanisms of action that hopefully make a very significant impact on preserving vision and potentially, halting progression as well as maybe even reversing disease, which is really exciting and innovative. [I would] love to see maybe more personalized medicine around predictive tools because as we have more treatment options, how do we sequence those options? How do we define what success looks like in this disease state if we’re just looking at a rate of growth? [I would] love to see more about any predictive tools that help us, not just identify, but then have the right shared decision approach that hopefully has and meets patient expectations, as well as payer needs and budget impact, and ultimately, making a significant impact on a clinically meaningful difference, which is about vision preservation.

Ryan Haumschild, PharmD, MS, MBA: Excellent. Clinical meaningful difference is really what’s going to carry us forward, I feel like, from a treatment selection standpoint. Dr Khanani, we couldn’t end without your thoughts on the evolving treatment landscape in the next 5 years. And also, what are some of your final thoughts and takeaways for our viewing audience?

Arshad Khanani, MD: Ryan, thank you again for moderating this great discussion. I really enjoyed it. I think the bottom line for me is that GA is a devastating disease that progresses 100% of the time, in 100% of the patients. And it’s a really severe disease that can take your independence away. It puts our patients in really tough situations. They cannot function and they go into depression. It really impacts the quality of life, and it leads to other comorbidities because the patients cannot see. Now, it’s a really exciting time to have the first FDA-approved treatment in pegcetacoplan [Syfovre], and hopefully, avacincaptad pegol coming in August. As physicians, there are still big unmet needs in this space. Obviously, complement inhibitors are a great start. It’s chapter 1 of a really thick book that we will write together over the next 1 to 2 decades. In the next 5 years or so, I think we have both of these approved treatments, hopefully, that we utilize in an appropriate fashion to help our patients. And I think having artificial intelligence to help us with finding the right patients, doing the right treatment interval, monitoring the growth will be important. Now, it’s exciting because we have so many things in the pipeline. Gene therapy programs, some of them are in phase 2 trials, where you are actually enriching a complement factor I, and kind of modulate the overactive complement system in bringing it towards normal complement activity. We have to wait for the data to see if that pans out. Treatment burden will likely be a big problem with frequent injections. Gene therapy, as Dr Lally said, with one-time treatment targeting the complement system in one way or another, whether in the operating room or in clinic, will be exciting. We have some other novel drugs and mechanisms of action that are in the pipeline. We saw some promising data from elamipretide to preserve mitochondrial function. There are other pathways we are looking at. But at this point, over the next 5 years, I think we will have to utilize the complement inhibitors in a fashion to help our patients preserve their vision. Final comments from me, it was very depressing over the last 15 years of practice for me to give the bad news of blindness to our patients with GA. Now I can give them some hope. They will be able to preserve their vision longer. Yes, we cannot reverse the disease. Yes, we cannot stop the disease. But slowing the disease down can have meaningful outcomes in the future because the treatment effect is greater the longer you treat these patients. And then, hopefully, we will have more treatments come down the pipeline and treat this disease early at the intermediate stage so we can actually tell our patients that you are not going to go blind.

Ryan Haumschild, PharmD, MS, MBA: Complement inhibitors sure are going to be a game changer in the field of GA. Thank you all so much. Thank you to our expert panelists for this rich and informative discussion, and to our viewing audience, we hope that you found this AJMC® Peer Exchange®to be useful and informative.

Transcript edited for clarity.

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