ACTRIMS 2022 | CLASSIC-MS: 8-10 year follow-up of ORACLE trial shows long-term efficacy of cladribine for MS

As you know, oral cladribine was originally licensed, and then it was not given approval, way back in 2011. And it got relicensed back in, resubmitted and licensed, back in 2017 to treat relapsing forms of MS. But some of the original trial populations weren’t followed up long-term. So we set up this CLASSIC study to try and track what happened to patients in the so-called original development program. And there were two trials, it was the CLARITY Phase III study and the ORACLE, which was clinically-isolated syndrome patients with a first attack going on to cladribine or placebo. And so what we try to do is, find as many people from the trial centers that were in the original trial to see what happened to them. And so that’s what we presented, is the portion of this long-term follow-up of these patients that were in the original ORACLE CIS trial.

And it was quite remarkable because, as you’ve probably known, the feeder trials were way back in the late 00s. So this gives us about a nine and a half year follow-up since they were last dosed because they were in the trial for about 18 to 24 months. And I think the remarkable result is that quite a significant number of these patients, despite not having any therapy, hadn’t converted to what we call clinically definite MS, having a second attack. So, there was a massive delay in a proportion of the patients, and I’ll give you the exact figures. So, of those patients that were exposed to cladribine in the ORACLE trial, over 50%, 53.2% of them, were attack-free, hadn’t had a defining attack since last study dose. And that compared to only 28.2% of those never exposed.

So, it was almost double the number hadn’t had an attack, so it was over 50%. So, that’s telling us a lot about the long-term efficacy. Now another metric we use is whether or not these patients have got any disability, and very few of them had disability. So of those that were exposed to the tablet, 98.7% of them were mobile, compared to 94.2% that weren’t exposed.

And when you look at the long term disability status, the majority of these patients, 97.4% of these patients, didn’t require any ambulatory device, compared to 94.4 in the never-exposed group. And those differences may seem tiny, but they are quite large when you think about the duration of follow-up from first attack. So, I think the overall message is that the… To me, this was the most surprising thing is, I would’ve expected a lot more patients to have converted to clinically definite MS, and I would’ve expected a lot more patients to be significantly more disabled, and they’re not. And this is telling us that oral cladribine, used very early in clinical isolated syndrome appears, at least from this dataset, and this is not the most wonderful dataset because it’s a… You’re selecting patients that weren’t in a trial, you’ve gone back to them retrospectively, but it’s the best we’ve got. And based on this dataset, it’s telling us that the efficacy of cladribine lasts a long time.

So that’s the take home message from the CLASSIC MS study, the ORACLE cohort of the CLASSIC MS study.