ACTRIMS 2020 News Network: B-Cell Depletion in the Phase 2 APLIOS Study

Clyde E. Markowitz, MD: In the APLIOS trial, the ofatumumab study, we know from the original phase 3 study that the data looked very impressive with regard to B-cell depletion. It was very effective on the metrics of relapse-rate reduction, MRI [magnetic resonance imaging], and disability progression, so it all looks good. The question we’re asking is whether a subcutaneous administration at the frequency that it is administered—which is at baseline, 7 days later, 14 days later, 28 days later, and then every month—at what point and how deep is the B-cell depletion? That’s really the question of this trial.

They looked at patients with multiple sclerosis [MS] and they were able to find that by 14 days, you had a quite impressive depletion to the point of having a minimal number of B cells. Essentially, everyone was depleted by 28 days. That was maintained. Since you’re administering every 28 days, that was maintained quite impressively to the level of a 1—B-cell conversation. This is a blood test that we’re doing to measure their B cells. What we never know is what the tissue B-cell numbers are looking like with any treatment. This is what ocrelizumab or ofatumumab. It doesn’t really matter. We know that there are different doses that are being administered. This is a 20-mg once-a-month dosage versus 600 mg every-6-months dosage for ocrelizumab.

We just don’t know what the tissue B-cell distribution is. We can at least say if we’re just measuring the blood, it’s quite effective in doing this. It mirrors what you see with ocrelizumab as well. Again, we just don’t have the ability to measure it in the tissue, so that’s going to be an unknown. At least from our standpoint, taking these data and applying them to the real world, we’re going to say it’s a very effective B-cell depleter. If you look at the data from the phase 3 clinical trial, you’ve got all the metrics of relapse-rate reduction, disability progression, and MRI that look very similar to what you get with ocrelizumab as well. I think there’s going to be a big added benefit to our MS treatment algorithms.