ASRS 2024: LUNA phase 2 interim data

Charles Wykoff, MD, PhD, gives an insight into first-time data from the phase 2, LUNA trial looking at Ixo-Vec at the annual ASRS meeting in Stockholm, Sweden.

Video Transcript:

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

Charles Wykoff, MD, PhD:

Hi I'm Charles Wykoff, retina specialist from Houston, Texas, and it's great to be here ASRS 2024 in Stockholm, Sweden. So at this meeting, we presented first-time data from the LUNA trial looking at Ixo-Vec, previously known as AVDM-022.

So ixo-Vec is an intravitreal gene therapy that leads to continuous intraocular aflibercept production, and over about 115 patients treated to date. We've seen consistent and strong efficacy at controlling exudative disease activity, and we've also seen notable levels of intraocular inflammation. So into that context, LUNA was designed as a trial, a phase 2 trial, to look at 2 main things: 1 was lower doses of Ixo-Vec, so lower doses of the of the virus that's being given as a gene therapy, and secondly, to look at enhanced steroid prophylactic regimens.

So 60 patients with wet AMD were randomized to 1 or 4 steroid prophylactic arms, and also a single injection of Ixo-Vec either 6E10 or 2E11, and then followed for what will ultimately be a 1-year primary endpoint, but at this meeting, we're presenting the completed 26 week pre-specified data. So enrolled patients were were heavily pre-treated patients with wet AMD on average 3 years since AMD original diagnosis and 10 mean annualized anti-VEGF injections at baseline vision was about 20/40, CST 350 microns. Let's talk about efficacy, and then safety giving each equal weight. So from an efficacy perspective, after Ixo-Vec dosing, we saw 76% to 83% of patients remaining injection free through week 26. We also saw stability in visual acuity through week 26, and also stability with CST through week 26. And maybe, to me, the most interesting efficacy signal that we saw was looking at the sub-population of patients that had a CST of greater than 300 microns at baseline. In that population of patients, I think, we really saw the anatomic stability achieved here through 26 weeks as those eyes with fluid at baseline actually had a reduction and CST at week 26 of minus 30 microns and CST stability through that 6-month endpoint.

So from a safety perspective, there were no Ixo-Vec related SAEs and all related adverse events were mild or moderate, the most common being dose-dependent, anterior chamber cellular inflammation as well as anterior pigmentary changes with 91% of patients in the local steroid regimen arms, having no or minimal inflammation at every visit through week 26. You know, again, of the key objectives of the trial was to evaluate these different enhanced steroid prophylactic regimens.

And so the key learnings from that were twofold. One, the dexamethasone-alone implant did not provide adequate prophylaxis, and therefore early in the trial, there was a protocol amendment that was incorporated to add difluprednate eyedrops to the OZURDEX alone arm. And once we made that change, we saw meaningful reduction in the IOI rates. And the second important finding, I think it's quite relevant to intravitreal gene therapy at large, was that the use of oral steroids, a meaningful relatively-high dose of prednisone over many weeks, did not provide additional benefit beyond local corticosteroid prophylaxis alone. Both of these things were findings that we did not know before the trial. This trial was designed to look at those 2 arms in particular, and both of them now we have much more clarity about what is useful for prophylaxis in this setting. Looking specifically at at the development of anterior chamber cellular activity or anterior chamber pigmentary changes.

When you look at the data from the patients with the prophylactic regimens that are being considered for future trials, we saw that most patients at most visits did not have cellular activity. There were 4 patients and both the difluprednate-alone, and the difluprednate plus dexamethasone populations that did have cellular inflammation and at least 1 visit, and there was also potential increase in anterior pigmentary cellular activity toward the end of the 26 week period. And then the last point about safety focusing in on the difluprednate-alone population. We saw in that group a dose-dependent dozens of anterior chamber cellular activity and anterior pigmentary changes through week 26. So in particular, in the lower dose, the 6E10 population, there was one patient at 26 weeks that had a very minimal amount of anterior cellular activity, and then 4 patients with anterior pigmentary changes, 3 of them being mild, 1 moderate.

So that was the summary of LUNA for ASRS 2024 It says 26 week completed data and a pre-specified endpoint and ultimately this will be a 1 year trial. Thank you.