Retinal experts from around the world brought their latest research to the virtual Angiogenesis, Exudation and Degeneration 2024 conference on February 3rd. Jennifer I. Lim, MD, FARVO, FASRS, director of the Retinal Service at the University of Illinois at Chicago, discussed some of the latest clinical data in nAMD and DME during her presentation. Watch this video to hear about her discoveries, including exciting advances in targeting Ang2 and her VEGF.
Note: This transcript has been lightly edited for clarity.
Hattie Hayes: Hello, I’m Hattie Hayes, editor of Ophthalmology Times Europe. Joining us today is Dr. Jennifer Lim, a speaker at this year’s Angiogenesis Symposium. Her presentation on the biology, pharmacokinetics, and latest clinical data in nAMD and DME is the topic of our discussion today.
Dr. Lim, thank you very much for joining us. Could you give us a brief overview of your presentation?
Jennifer I. Lim, MD, FARVO, FASRS: Yes, I’d be happy to, Hattie. Thank you for being here today. During my presentation at angiogenesis, I discussed some of the new findings regarding faricimab. One is that we actually sampled angiopoietin 2 levels from the aqueous humor of patients with DME and AMD. And we showed that administration of faricimab actually reduced angiopoietin-2 levels, whereas this did not occur with aflibercept. So this confirmed that faricimab, a bispecific anti-Ang2 and anti-VEGF, was indeed targeting Ang2 based on the pathophysiology of the disease. And we know that angiopoietin-2 plays a role in AMD and diabetes. Increased Ang2 has been shown to cause blood vessel instability. This, in turn, leads to destruction of blood vessels, which naturally results in exudate and fluid in these eyes, which becomes clinically visible.
The second point is the fact that the way a clinical trial is designed can influence the durability actually achieved. So, for example, in the faricimab study, the interval was limited to his Q16 week. And actually, when we went back and looked at the retreatment criteria, we based it on no vision loss, no fluid gain, or in the case of nAMD, no bleeding, for example. Applying the same criteria for DME and AMD eyes and applying it to patients who have already achieved every 16 week interval, what percentage of those patients theoretically could have been dosed in Q20 weeks? . And it turns out that more than 50% of patients with DME and AMD can actually be dosed at 20-week intervals. So this points to the fact that study design can influence actual findings. We also analyzed data on the retreatment criteria themselves. For example, when we looked at the data for faricimab, we said, “If we see decreased vision, increased retinal thickness, or hemorrhage, we’re going to regress.” Now, let’s say we turned that around. And let’s say… as has been done in some other studies, that the visual acuity is reduced and there has to be some increase in retinal thickness or there is blood present. Q: What percentage of eyes were able to achieve 12 weeks or more? And he found that the number increased significantly from 70% to 95%. Therefore, once again, the design of a clinical trial can influence outcomes.
Finally, we also introduced real-world data. We specifically looked at all databases such as Vestrum, and also mentioned other real world databases such as FARETINA, TRUCKEE, and TAHOE. Of course, you know these were discussed by other speakers during angiogenesis. And basically, what they all showed was that the incidence of inflammation within the eye was no higher than what was observed in clinical trials. And finally, his IOI rates for BALATON and CAMINO retinal vein occlusions were also very low, consistent with those observed in AMD and DME. So I think it shows that faricimab is hitting its intended target, achieving durability, and maybe durability could have been even longer, and that it was done in a safe way.
Hattie Hayes: Is there anything in your presentation that you think others might find surprising or innovative?
Dr. Lim: Well, the fact that the design of a clinical trial can have a significant impact on the results obtained, and that changing the inclusion criteria or increasing the options for interval extension may actually result in I really think that there is a gender. This is probably similar to what we see with aflibercept 8mg, for example. Therefore, you need to be very careful when looking at the results to understand how the design affects the results.
Hattie Hayes: What are the key takeaways that you hope conference attendees will take away from this research?
Dr. Lim: The important thing, as you probably know, is that angiopoietin-2 is a really important target. We confirmed this in the phase 2 RUBY study, providing the first evidence that the combination of Ang2 and anti-VEGF can yield results. And in the study of faricimab, we see the fact that if you look at direct administration, you can quadruple the anti-VEGF dose. That was also done at Lucentis, where they found that quadrupling the ranibizumab dose did not provide any anatomical benefit. This was also true of his HARBOR research. [inaudible]. We also found that even if he quadrupled the dose of aflibercept, as was done with PHOTON and PULSAR, there was no improvement in anatomical events. So there’s something to be said for Ang2 inhibition in combination with anti-VEGF, and I really think it’s biologically plausible. And in fact, we now have real anatomy and outcomes and anatomical evidence to show that there is some impact on patients.
Hattie Hayes: wonderful. Dr. Lim, thank you so much for speaking with me and sharing your research.
Dr. Lim: you’re welcome. Thanks for having me, Hattie.
