Designing More Effective Proof-of-Concept Studies for Progressive MS Therapies: Robert J. Fox, MD

WATCH TIME: 3 minutes

"I think we don’t know what is the right answer [biomarker] to use in a proof of concept phase 2 trial. My general recommendation would be when people ask what is the best metric, we say we don’t know the best metric so we do the next best thing. That is to measure a bunch of things and look for coherence in the benefit of a therapy on those outcomes. Look at whole brain atrophy, the compartmentalized atrophy like cortical atrophy and deep gray matter."

Despite the advances in disease-modifying therapies (DMTs) for relapsing forms of multiple sclerosis (MS), developing agents that work on the progressive aspects of the disease have been much more challenging. Part of the issue of identifying an effective therapy comes from locating disease-altering biomarkers that correlate with scales of functional change. Several in the field, including Robert J. Fox, MD, have conducted numerous studies assessing the impacts of several prominent central nervous system biomarkers, such as neurofilament light (NfL) and glial fibrillary acidic protein (GFAP).

At MSMilan 2023, the joint ECTRIMS-ACTRIMS meeting, held October 11-13, in Milan, Italy, Fox and his colleagues presented data from the notable SPRINT-MS trial assessing GFAP and Contactin-1 as treatment response biomarkers in progressive MS. In a cohort of 255 patients with either primary progressive or secondary progressive MS, serum GFAP was 2.202% higher with older age and 19.467% higher in women (both; P <.001). Over 96 weeks, estimated change in serum GFAP was 2.88% increase/year in placebo and 2.13% increase/year in ibudilast-treated patients (P = .068). At the same time, investigators observed a 2.69% decrease/year in cerebrospinal fluid GFAP in those on placebo and 0.29% decrease/year with ibudilast (P = .62).

Following the presentation, Fox, neurologist, Mellen Center for Multiple Sclerosis, and vice-chair for research, Neurological Institute, Cleveland Clinic, sat down to discuss the complexities with understanding treatment response in progressive MS, and some of the prominent biomarkers currently being used. He provided perspective on the need to build better phase 2 proof-of-concept studies that incorporate biomarker analyses and allow for a true detection of clinical efficacy.

Click here for more coverage of MSMilan 2023.

REFERENCE
1. Fox RJ, Harvey T, Veld SI, Plaga A, Teunissen C. Evaluating GFAP and Contactin-1 as treatment response biomarkers in progressive MS. Presented at: MSMilan; October 11-13, 2023; Milan, Italy. POSTER 265