Envision Summit 2025: PULSAR phase 3 trial 96-week post-hoc analysis

At the Envision Summit 2025 in San Juan, Puerto Rico, Deepak Sambhara, MD, gave insight into the 96-week post hoc fluid outcomes analysis of patients who participated in the phase 3 clinical trial PULSAR.

Video Transcript:

Editor's note: The below transcript has been lightly edited for clarity.

Deepak Sambhara, MD:

Hi, I'm Deepak Sambhara, partner and medical director of research at the Eye Clinic of Wisconsin. We're here at beautiful San Juan, Puerto Rico at the Envision Summit in 2025, where I have the great privilege to present the 96-week post hoc fluid outcomes analysis of patients who participated in the phase 3 clinical trial PULSAR, based on baseline demographics.

Now, as we're all aware, PULSAR is a pivotal phase 3 clinical trial that assessed the safety and efficacy of the aflibercept 8mg in the setting of treatment-naive neovascular AMD. Patients are randomized in a 1:1:1 fashion to receive afliberept 8mg, either every 12 weeks or every 16 weeks after initial three monthly injections, or aflibercept 2mg every eight weeks after initial three monthly injections. There was a primary endpoint of visual acuity, non inferiority that happened at week 48 and a key secondary endpoint of proportion of eyes with fluid free retinas at week 16.

Now, importantly, pulsar met both its primary and secondary endpoint with a high degree of statistical significance and visual acuity and anatomic outcomes that were seen in week 48 persisted through week 96. Importantly, patients in the aflibercept 8mg group, were able to do so with fewer overall treatments.
Now, one of the beautiful things about the analysis that we performed and I presented today, is we were looking at fluid outcomes based on specified criteria at three specific time points; week 16, week 48 and week 96. Importantly, what we found was irrespective of baseline criteria, and that included baseline CRT, baseline visual acuity, baseline CMV lesion subtype, as well as baseline fluid location. Patients who received aflibercept 8mg and 2mg achieved similar proportions of fluid free retinas at those three time points. Importantly, with the eight milligram group able to achieve these outcomes with fewer overall treatments.

Finally, the last interesting thing about this analysis is we did a match dose post hoc analysis. Now, one of the limitations of PULSAR is direct head to head comparisons that happen after week 12 or week 16, due to the fact that there's asynchronous dosing that occurs. Meaning that if you were in the 8mg aflibercept group, you could receive injections as often as every eight weeks, or as little as every 24 weeks due to interval shortening or interval extension. Well, if you were in the aflibercept 2mg group, you were getting fixed dose injections every eight weeks. In order to make more apples to apples comparison, this post hoc, matched-dose analysis was performed looking at anatomical outcomes eight weeks after each active matched injection. And what we found was that patients who received 8mg aflibercept were able to achieve fluid free retinas at a numerically greater value that ranged from 14-23% eight weeks after each active matched injection. That was also translated into anatomic findings, where CST improvements were greater in the 8mg group eight weeks after each active injection relative to the 2mg group.

So it's a really cool presentation. I'm glad I got the chance to present it. The alternative, honestly, is six inches of snow where I am in Wisconsin, so I'm having a great time here with the family. Encourage everybody to attend this meeting in the future, if you hadn't had the chance to.