This article was originally published in a sponsored newsletter.
For this month's Retina Minute, I have the privilege of interviewing my good friend, Ramin Tadayoni from University Paris Cité, Lariboisière and Rothschild Foundation Hospitals in Paris, France.
Ramin, you recently presented some breaking data on the BALATON and COMINO trials. Can you explain to our readership what the BALATON and COMINO trials were, how the studies were designed, and what they showed?
These were 2 studies about faricimab (Vabysmo, Genentech) in retinal vein occlusion (RVO). BALATON is in branch retinal vein occlusion (BRVO), and COMINO is in central retinal vein occlusion (CRVO) and hemi-central vein occlusion. They were phase 3 trials, and they had 2 parts. The first part was for 6 months in which monthly injections of faricimab were compared to monthly injections of aflibercept (Eylea, Regeneron), and the primary endpoint was at week 24 that compared the visual gain between the 2. I presented that data last year at Angiogenesis, and it has been published.
Now, we have the second part of these trials over an additional year, during which all patients received faricimab: Patients who had 6 months of faricimab continued with faricimab and those who had aflibercept switched to faricimab out to week 72. All patients started at the same duration and then were in a modified treat-and-extend regimen to see how much their dosing schedule could be extended. We continued injections as far as patients improved. When we reached stability, we increased the interval, but if there was something wrong, we decreased the interval. We increased or decreased schedules by 4-week intervals.
Demographics were similar to what was presented previously because it was the same patients from the first part of the trials. In terms of age, everything was balanced between groups. Visual acuity was a bit lower in CRVO compared to BRVO, which we are used to, and central subfield thickness (CST), of course, was higher in CRVO compared to BRVO, but there was no imbalance between groups.
During the first part of the study, all patients gained around 17 letters on both faricimab and aflibercept, so the results were comparable. And the benefit at that time was that there was less leakage on fluoroscein angiography (FA) with faricimab compared to aflibercept. With less leakage, you expect that you can extend.
On average in the second part of the study, patients received approximately five injections of faricimab. It was possible to increase the interval for most patients beyond 12 or even 16 weeks. However, visual acuity remained stable and even increased by a mean of one letter in BRVO, despite the lower number of injections. CST was also stable. While visual acuity did not change, the gain, which was impressive during the first part in BRVO and CRVO, was maintained. That result shows that faricimab can be used long-term in patients with BRVO and CRVO, and can also be used as an alternative for patients treated with aflibercept with good results.
In terms of incidents of side effects, there were no surprises and no vasculitis. Everything seems safe and faricimab was well tolerated.
Faricimab is approved in the United States for RVO, and approval for other countries is expected depending on the duration of administrative paperwork.
What percentage of each group had retention for the second 6 months?
It was high, perhaps more than 90%.
What was the maximum extension allowed in the treat-and-extend arm?
16 weeks.
And what percentage of patients in each group were able to go 16 weeks?
In BRVO it was around 50%, and in CRVO it was 37% to 39%. For 12 weeks or longer in BRVO, it was around 60% and in CRVO it was 45% to 50% for CRVO. So nearly half of patients were Q12 or more in CRVO and 60% in BRVO.
What was the number of patients that ended up with either neovascularization of the retina or neovascularization of the iris?
I believe it was zero, but analysis is ongoing and results will be presented and published when ready.
Once faricimab gets approved in France, how do you intend to treat people? Do you intend to switch patients to faricimab? Do you intend to start them from scratch? How do you see it integrating into your practice?
I will probably use it from scratch. There is no reason not to use it from scratch. This data shows that it is possible to switch patients and they will do as well as if you treated them from scratch with faricimab.
You mentioned that there was less leakage in the head-to-head phase at the beginning. Were the patients who had less leakage able to be extended longer?
We do not have that information. We have the first results, but there will be many other questions to look for.
Ramin, I truly appreciate the knowledge. Our readers are thrilled to hear this breaking news. This represents another tool in our toolbox to treat retinal vein occlusion, which previously was treated almost monthly, but now with faricimab, as BALATON and COMINO showed, 57% of BRVO patients and 45% of CRVO patients can go 12 weeks or longer. That will definitely decrease the treatment burden and hopefully increase compliance. So thank you so much for sharing this with us today.
Thank you very much.
