Ofatumumab Safety Data and Novel Approaches to MS

Stephen Krieger, MD: Ofatumumab is obviously a more modern B cell depleter, and one of the real interests that we all have, especially now, is the risk of infection and the risk of COVID-19. Hauser et al presented the clinical trial extension data on the risks for serious infections and COVID-19. It was a "good news" report, in essence—there are only 4% of people who've been in the clinical trials for ofatumumab who developed a serious infection, and the vast majority—over 90%—of those fully recovered. So that's comforting.

Then, there is the timely issue of COVID-19, and it's really quite remarkable when you think about it. They looked at a couple of thousand patients that have been followed after the ofatumumab pivotal trials. So this is not a real-world dataset, this is the clinical trial cohort, and almost 300 of them developed COVID-19 during this period of time. Again, reassuring in that the vast majority of those were mild to moderate infections, and the fatality rate from COVID-19 in these ofatumumab-treated patients was around 1%, which as we know from these past couple of years, is in line with the overall risks of mortality with COVID-19. So it was not higher than what we would have expected. On balance, I think that's a reassuring set of outcomes. My hope is then, in the next extension trial cut for these data that we won't see quite as many COVID-19 cases anymore. But so far with ofatumumab, that was reassuring news.

I think one of the interesting things that is happening now in the field of MS is we're shifting our focus from mechanisms of treatment that we've had to novel ones like the [Bruton tyrosine kinase] inhibitors. And we're also getting to look at the efficacy of our existing therapeutic strategies with novel metrics. This is really exemplified by the idea of looking at slowly expanding lesions or chronically active lesions. So, briefly, there were data shown for ofatumumab in minimizing chronically active lesions, looking at that on PET scans. So, not something we do in regular clinical practice, but showing that peripheral B-cell depletion may shut down that chronic active lesion formation in the brain. Then we also saw that from evobrutinib, which is one of the BTK inhibitors now in clinical trials. That also shut down the formation of these slowly expanding lesions from their phase 2 trial data, and Doug Arnold, MD, presented that.

It kind of exemplifies the change in the conversation about MS pathogenesis, looking at the way these treatment strategies affect the activated microglia causing these enlarging lesions. We've seen that from the evobrutinib trial campaign, we're starting to see data like that from tolebrutinib, another BTK inhibitor in trials now, and I think we're only going to see more of that in the years to come.

Transcript edited for clarity.