Timothy G. Murray, MD, MBA (00:16):
Hi, I'm Dr. Timothy Murray, co-director of the Aspen Retinal Detachment Society meeting, coming to you from Snowmass Mountain. It's my pleasure to introduce our excellent speaker, Dr. Jacque Duncan, who spoke with us on Encelto for MacTel: Potential and Pitfalls. So Jackie, welcome. Thank you. You gave an insightful talk with a lot of discussion. Can you take me through, you talked about both the potential, but you've also spoke to the pitfalls.

Jacque L. Duncan, MD (00:50):
Well, I think that it's always important when a new technology or treatment comes along to think about the evidence that supports its development and its use. And importantly, to think about the research that led to it becoming approved by the FDA so you can make the best recommendation for your patients. So the presentation really focused on a disease called macular telangiectasia, which didn't really have any FDA approved therapies until this treatment, which was called Encelto or revakinagene taroretcel, which is a very innovative way of delivering a growth factor protein on a long-term basis into the eye. It uses transformed retinal pigment epithelial cells that have been treated so that they secrete ciliary neurotrophic factor, a growth factor into the vitreous on a long-term basis. Even up to 14 years, this device has been demonstrated to secrete this protein at meaningful levels. It's surrounded by a membrane that allows the protein to get out, but prevents inflammatory cells from recognizing these foreign cells and causing inflammation.

(02:00):
So two pivotal multicenter randomized clinical trials investigated this treatment in patients with macular telangiectasia. And some patients were randomized to receive a sham treatment and some were randomized to receive this therapy. And two separate trials were done, which both showed significant reduction in the rate of disease progression. One of the two trials showed a much bigger effect than the other. And I spent a little bit of time talking about that difference between the two trials in my talk.

Timothy G. Murray, MD, MBA (02:33):
You also mentioned though about visual acuity and function as an outcome. So there were negatives to this therapy.

Jacque L. Duncan, MD (02:40):
Whether they were negatives or just less positives than one would hope, it's hard to say. So macular telangiectasia causes a lot of visual disability, but it spares the fovea for a long time. So visual acuity is actually a very insensitive measure of disease progression. For this reason, the trials were designed using a structural outcome measure of ellipsoid zone atrophy. The studies showed that the ellipsoid zone atrophy progressed slower in the eyes randomly assigned to receive the Encelto than the eyes that got sham. But the difference between the sham and the treated eyes was much smaller in one of the two trials than the other. And in both the trials, there was no significant benefit in terms of visual acuity or microperimetry, visual sensitivity. So even though the structure looked better in the eyes that received the treatment, the visual function was not different between the sham and the treated eyes.

Timothy G. Murray, MD, MBA (03:35):
So what's the take home message now that we have an FDA approved device, a known surgical procedure for an untreatable condition?

Jacque L. Duncan, MD (03:43):
Yeah, a previously untreatable condition, correct. So I think for patients that were similar to the ones that were enrolled in the trial, having some atrophy of the ellipsoid zone, but not too much, not more than two millimeters of atrophy, I think this is a treatment that would be recommended for patients to try and preserve their vision as long as possible.

Timothy G. Murray, MD, MBA (04:02):
Jacque, it was exciting, interesting, a novel biofactory proof of principle. I thought it was very, very exciting. So thank you for speaking with us.

Jacque L. Duncan, MD (04:12):
Absolutely. My pleasure. Thanks for having me.