Risk-Benefit of Geographic Atrophy Treatment

David Lally, MD: What we've seen from both of these complement inhibitors that have been FDA-approved is that they have a treatment effect for patients and to the benefit of slowing progression of disease. Albeit, the treatment effect of the rates of what they can do and lowering the progression are not as high as we'd like to see, it's still a landmark time, as we have for the first time in our history, a tool that we can use that can alter the progression path of geographic atrophy.

These treatments do have small, but important side effects that I counsel with my patients that they need to be aware of. We saw that complement inhibition can be associated with increased risks of developing the wet form of macular degeneration called choroidal neovascularization. This is when new blood vessels can grow in the retina and leak fluid and/or blood into the retina. It can negatively impact the central vision if that occurs. If that occurs, I tell my patients, the good news is that we have good treatments to treat wet macular degeneration. They're good effective treatments that we've been treating patients with wet macular degeneration for over 10 years now. So it is a complication that we can do something about to help patients.

In terms of the other risks we think about there's always a risk of inflammation with any drugs that we inject into the eye. That's something to that I counsel patients on, there's always a risk of infection anytime we inject a needle into the eye. Then, the other thing we saw is that there were rare reports of what we call ischemic optic neuropathy, which can negatively affect vision. These were rare cases. And in the the SYFOVRE trial, there was only one case seen with the every-other-month dosing arm. The other cases were seen in the monthly arm. And in the IZERVAY trials, there was only one case observed in the first trial. We don't really know if these drugs cause that problem yet, because the numbers were still small. These numbers were not seen in the sham group, so we consider it as a possible side effect at this point.

Those are the side effects that I counsel my patients on, they're all low side effects. For the vast majority of patients, the treatment benefit would outweigh those risks. In terms of where I see the landscape going in the future in the treatment of geographic atrophy, the first place we would see it going would be the development of complement inhibitors that have more durable treatment effects that lasts longer for our patients. So our current treatments are either monthly or every-other-month intravitreal injections, with no stopping. That's indefinitely with the patient. That's a high treatment burden for patients to come in so frequently for eye injections.

There are a lot of companies already that are out there in early development, working on medicines that we can deliver to patients eyes that release complement inhibition for a longer period of time. Some of those therapies being developed aren't even injections in the eye. There are some companies out there looking at subcutaneous injections, or other routes of administration to last longer for patients to reduce treatment burden for patients. The other place is where people are looking is just a different mechanism of action. You know, we saw the complement in inhibition has a treatment effect but not to the level we would hope for, there's still a long way to go in treating this disease.

There's many other types of mechanisms of action that are likely involved in this disease that have yet to be discovered. A lot of companies are out there working on treatments, hoping that we can get better slowing of progression of geographic atrophy with the ultimate goal being someday to restore the vision and restore that tissue to get patients seeing better. We've come a long way with these new therapies. That was a big landmark change in the field of treating geographic atrophy, but we still have a long way to go.