The Promise of Frexalimab in MS: Part 3

In part 2 of this interview, Patrick Vermersch, MD, PhD, University of Lille, France, discussed next steps in the evaluation of frexalimab in multiple sclerosis (MS), the findings that have surprised him the most, as well as explored if frexalimab could one day be considered for conditions other than MS.

In the third and final part of this interview, Vermersch detailed the adverse events encountered in studies of frexalimab treatment and explored the criteria necessary to establish the drug as a widespread treatment for MS. Results from the phase 2 frexalimab trial are currently published in The New England Journal of Medicine.

This transcript has been lightly edited for clarity and length

Transcript

AJMC: Were any adverse events observed in the phase 2 trial? How will they be mitigated moving into Phase 3?

Vermersch: So it's a critical point, of course, there are 2 phases for drugs for efficacy and also safety. Of course, it's a relatively most small cohort of patients, around 150, and a short period of follow-up. You know, the data we have published we will present the extension until week 48 at the next American Academy meeting, but the published data and presented data at the last ACTRIMS was until week 24. The data are definitely reassuring. We have no surprises, no safety signals, we have a couple of patients with infections, but very few—and maybe probably no more than the global population. We have a couple of COVID-19 patient, decreases and increases in fatigue, we have only one cancer—papillary thyroid cancer. Of course, we don't know if there is a link or not with the drug. So, today, no safety signals. Of course, we need to wait more, we need to have, obviously, data from phase 3. [We need] the long term data because we know the frexalimab—anti-CD40 ligand— impact on death and the immune system. So, of course we need to have more robust data to maybe to be sure the drug is safe, but no safety signals. So, of course considering the efficacy, it makes sense that we need to go very quickly to phase 3 studies.

AJMC: What criteria does frexalimab need to meet moving forward to become widely available in a clinical setting?

Vermersch: Of course, the phase 3 relapsing study will be done vs an active drug, teriflunomide, and we need first to demonstrate superiority. The criteria that we need to have to maybe adopt [frexalimab] as a standard of care is not only superiority on the number of relapses, not only the superiority considering the MRI activity, but probably more to demonstrate an efficacy of superiority for disability progression in both relapsing remitting and, even more, in the progressive study of nonrelapsing SPMS because we need to consider not only this drug, but the drug we have today. For example, in the efficacy of the drug natalizumab—an anti-CD20—we have a robust activity in relapsing MS. So, maybe to be the standard of care, we need to have more robust data at least as we have with natalizumab anti-CD20, but also possibly a very strong impact on disability progression. I mean, disability progression, not only on the EDSS, but also some composite scores, walking capacities, ability to use the upper limbs, qualitive functions, fatigue, and also some biomarkers like neurofilament, brain atrophy, and maybe some patient-related outcomes. So, we need to consider many criteria for frexalimab to maybe one day be considered as a standard of care.