Updates on NfL Levels in MS Clinical Trials

Bruce Hughes, MD: In Boston [at the American Academy of Neurology Annual Meeting], we’ve seen several exciting posters and presentations about NfL [neurofilament light chain]. One looked at the phase 2 RADIANCE clinical trial. They showed that assessing NfL levels in patients treated with ozanimod could show a decrease as soon as 4 weeks after treatment initiation. Those levels continued to decrease throughout the monitoring period for the 24 weeks, when they hit the lowest level yet.

The RADIANCE trial poster also showed that sustained decreased levels of NfL correlated directly with reduction in gadolinium-enhancing lesions. Also in Boston, the Enrique Alvarez group demonstrated that ofatumumab had a sustained suppression on NfL in its clinical trial. It showed that individuals who had been treated with ofatumumab had sustained in low levels of NfL. This study had a comparator arm of teriflunomide. At the end of the study, when patients transitioned from the ASCLEPIOS trial to the ALITHIOS trial, patients who were on teriflunomide were transitioned to the ofatumumab group. They demonstrated that once they transitioned, those patients had a sustained marked reduction compared with their baseline level on teriflunomide in their levels of neurofilament light chain. When investigators looked at this overall—at the initial pivotal trial and then the follow-up trial after patients had transitioned—those who had been on ofatumumab from the get-go, not on teriflunomide, tripled their chance that they had attained NEDA-3. That means no evidence of disease activity: no disability progression, no new MRI lesions, and no new relapses. It was impressive to have a tripling in response.

Also presented in Boston was a poster on the novel BTK [Bruton tyrosine kinase] inhibitor line of treatment and its impact on NfL levels. This was specific to evobrutinib, which is a BTK inhibitor. None of these agents has FDA approval for treatment in multiple sclerosis, but many are being studied. It’s an exciting new avenue of potential treatment options for the future. Investigators showed that there was a sustained lowering of NfL levels that correlated with improved MRI and relapse outcomes for those patients in the evobrutinib arm.