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ECTRIMS 2021 | Phase III ULTIMATE I & II update: ublituximab versus teriflunomide in relapsing MS

Lawrence Steinman, MD, Stanford University, Stanford, CA, shares the latest data from the Phase III ULTIMATE I and II trials (NCT03277261; NCT03277248) of ublituximab versus teriflunomide in relapsing multiple sclerosis (MS). Over 1000 patients were randomized 1:1 across the two identical multicenter double-blind trials, which assessed annualized relapse rate (ARR) as the primary study endpoint. Ublituximab was shown to reduce ARR by 50-60% relative to teriflunomide. Contrast enhancing T1 lesions and new/enlarging T2 lesions were both decreased by over 90%. Additionally, ublituximab administration resulted in significantly better disability improvement at 12 and 24 weeks, compared to teriflunomide. Dr Steinman outlines the newly reported brain volume and multiple sclerosis functional composite (MSFC) score outcome data. This interview took place at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) congress 2021.

Transcript (edited for clarity)

The primary endpoint in the ULTIMATE I and II trials was the annualized relapse rate, and in both trials, the annual relapse rate was 50 to 60% more favorable than the comparator, which was teriflunomide. And for the first time in any of the anti-CD20 trials, the annualized relapse rate went below a 10th of a relapse a year. I like to go into a room and tell a patient when I would quote from this trial that it could mean something like that the chance of getting a relapse might be one in 10 years...

The primary endpoint in the ULTIMATE I and II trials was the annualized relapse rate, and in both trials, the annual relapse rate was 50 to 60% more favorable than the comparator, which was teriflunomide. And for the first time in any of the anti-CD20 trials, the annualized relapse rate went below a 10th of a relapse a year. I like to go into a room and tell a patient when I would quote from this trial that it could mean something like that the chance of getting a relapse might be one in 10 years. Of course, that’s not an exact mapping of the result, but it was a noteworthy result because no one has ever shown with any of the anti-CD20 reagents an annualized relapse rate that low. The other end points, the secondary pre-specified endpoints included remarkable reduction in gadolinium enhancing T1 lesions and a reduction in T2 lesions.

A third point that I think was very compelling in the trial was the fact that there was confirmed disability improvement that was statistically significant in a pre-specified analysis compared to teriflunomide. So it’s another very important point that you could tell an individual with MS who was getting advice about different things to us, that in this trial there was evidence of improvement.

The brain volume studies showed that teriflunomide in the short run actually leads to an increase in brain volume. In a post hoc analysis, when the data were analyzed, the rate of decline was essentially similar between the teriflunomide group and the group getting the ublituximab, if not for that early improvement that’s known to occur with teriflunomide.

And that was a very exciting in a poster presentation where we went into it in detail. The MSFC tests showed a remarkable improvement again in performance, and it’s a multiple test that includes a number of features. But again, it’s very reassuring to individuals to know that not only does disease get stabilized, but there’s actually improvement, and that’s something we all hope to be able to have for individuals with MS. That’s, I think, a comprehensive review of the situation with ublituximab. I’m very excited about it, and I thank the individuals who participated in the trial. I think there’s a lot to show for it, so thank you.

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Disclosures

Dr Steinman consults for TGTx.