Extending Treatment Intervals with Durable Therapies for nAMD and DME - Episode 3
M. Ali Khan, MD, FACS, FASRS, reviews the PULSAR and PHOTON clinical trials of high-dose aflibercept for treatment of nAMD and DME.
Rishi P. Singh, MD: Recently, we’ve had the high-dose aflibercept 8 mg, which was approved by the FDA and PULSAR and PHOTON. What are some of the clinical outcomes from this trial that stand out to you?
M. Ali Khan, MD, FACS, FASRS: So PULSAR and PHOTON, I think with the approval of faricimab, the 16-week mark became a very attractive time point that everyone’s looking at. So with the PULSAR and PHOTON looking at DME [diabetic macular edema] and neovascular AMD [age-related macular edema] with the high-dose aflibercept. In PULSAR, there was about 88% of patients who were on a 12-week or more dosing interval by the end of 2 years, which was a significant proportion. And then in PHOTON, that number was about 89% of patients were on a 12-week or more treatment interval. In these 2 trials, they even allowed criteria to go longer than 16 weeks. And in both trials, there was a decent percentage of patients who can actually achieve that. In the PULSAR trial, the [number of patients who] could reach up to even 24 weeks was approximately 28%. And about 27% in the PHOTON study for 24-week dosing. So it achieved a similar duration and level of interval that we’re noticing with the faricimab trial and potentially even a bit longer. And most of those intervals were maintained for the majority of those patients for the entire 2 years.
Rishi P. Singh, MD: I think that you’re absolutely correct about that 12-week holy grail. And now it’s gone to 16 weeks and even 20 weeks. And like you said, I think the numbers speak for themselves both for PULSAR and PHOTON. What I think was interesting was that the week 20 was a durable agent into year 2, which I thought was very, very interesting because I didn’t expect it to go that long. I think honestly, we thought that most patients need to be monitored every 3 months as most. If we got 90% of people to 3 months, probably we would have a very durable agent that we could all use. And this actually went even 20 weeks, which I think is probably longer than we did. And I think in clinical practice, we might choose to just see these patients back quarterly regardless of that because in the fact, we want to make sure that we follow them, make sure they don’t have any sort of changes in their OCT [optical coherence tomography] or visual acuity that might be silent and not necessarily evident to the patient. So it’s important, I think, [that] we follow these individuals as closely as we can despite the great durability that we saw of these patients over time. In addition to the fixed-dosing arm, clinical trials for both these drugs used [a] treat-and-extend arm, can you discuss some of these prespecified criteria on shortening or extension of the intervals?
M. Ali Khan, MD, FACS, FASRS: I think to help mirror clinical practice, both trials did have the treat-and-extend portion after year 1. So, in year 2, you were able to extend your interval and the prespecified criteria were based on OCT, central subfield thickness, visual acuity letters, and then for the neovascular AMD trial, also the presence of submacular hemorrhage, as you mentioned. So these were very tight criteria, so everyone was on the same page in terms of who can extend and who couldn’t.
And again, these could be up extensions to 4 weeks either way, either reduction or an extension. So I think those prespecified criteria were made, for both the faricimab trials and the high-dose aflibercept trials,…in a way that mirrors mostly what we do with clinical practice.
Rishi P. Singh, MD: I would agree with you. I think that the ability for you to pick both anatomy and vision at any given time, and, by the way, investigator discretion in both studies was allowed to change the interval as well. So it just wasn’t based upon one and the other per se. It was also investigator discretion. So they could have determined if the patient met a criteria that they saw clinically or what have you, that they could actually change that based upon that. So that was, I think, a very important finding as well.
Transcript is AI-generated and edited for clarity and readability.