Unmet Needs and the Evolving Treatment Landscape of Multiple Sclerosis

Benjamin Greenberg, MD, MHS, Director, University of Texas Southwestern and Children’s Health Neuroimmunology Program, discussed the unmet needs and upcoming developments in the diagnosis and treatment of multiple sclerosis (MS) during a virtual presentation given at Neurology Week.

During his state of the science presentation, Dr Greenberg focused on:

• Prognostics and Markers of Response to Therapy

• Disease Modifying Therapy

• Restorative Therapies

Dr Greenberg emphasized that these topics are some of many things going on in the realm of MS.

According to Dr Greenberg, an unmet need in the treatment of MS is the technology to track disease activity in a patient in real time, similar to tracking the glucose levels in patients with diabetes.

“We start on one medication and determine if somebody is responding or not, and we define that success as the absence of relapse, the absence of MRI changes, the absence of disability progression,” Dr Greenberg explained. “But we can only judge those successes in hindsight, so we have to wait a period of time to see are we having relapses or not, MRI changes or not, progression or not. So, a critical unmet need within multiple sclerosis is a technology that can track the patient’s disease activity in real time.”

The presentation highlighted Neurofilaments Light chain (NfL) as the most abundant subunit of neurofilament, and a biomarker of disease activity in patients with MS. Serum NfL increases with atrophy. In patients with MS, neurofilaments in the spinal fluid can be on average four to five times the level of a healthy control.

Technologies for measuring serum NFl include NFl ELISA, electrochemiluminescence (ECL)-base immunoassays, and Simoa, single molecular arrays which are more sensitive than ELISA and ECL.

“From a biomarkers perspective, serum neurofilament is something that's garnered a lot of attention appropriately and I wouldn't be surprised if we start seeing this in the clinical setting over the next one to two years,” Dr Greenberg said.

This is one of many examples around developing prognostic markers or markers of response to therapy.

The landscape of MS treatment is evolving, with more oral therapies being introduced and FDA-approved over the last few years.

Dr Greenberg’s presentation called out Bruton’s Tyrosine Kinase (BTK) inhibitors, in particular, as an emerging drug class for treatment of MS.

Inhibiting BTK can target the adaptive immune system. Small-molecule inhibitors of BTK can be beneficial to inhibit the activation of autoreactive cells.

While this has been a focus area for cancer research, particularly for hematologic malignancies, Dr Greenberg explained there are therapeutic opportunities for patients with MS regarding autoantibody production and B cell function, as well as macrophage activation that could reduce neurodegeneration. The presentation noted late stage clinical trials are in progress for BTK inhibitors evobrutinib, tolebrutinib, and fenebrutinib.

This is a new biology for clinicians treating MS to understand, Dr Greenberg emphasized.

“So, if you take anything away from this and again, I'm only scratching the surface, I would impress upon you that multiple sclerosis is a very complex heterogeneous condition with a lot of effective therapies, but several unmet needs,” Dr Greenberg concluded. “I would put the top two unmet needs as prognostic markers and response to therapy markers, and then therapies that impact neurodegeneration.”

—Erin McGuinness

Greenberg, Benjamin M. Introduction and State of the Science. Presented at Neurology Week 2021; July 14-18. Virtual.