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MS Leaders Detail Progressive MS Research Advances, Challenges


The lack of biomarkers for progressive multiple sclerosis has made the development of new treatments much more difficult for this form of the disease.

There is a huge unmet need for new treatments for patients with the progressive form of multiple sclerosis, which is characterized by a slow progression of the disease. But promising developments in research are under way, MS leaders said during the International Progressive MS Alliance’s Ending Progressive MS Webinar.

Robert Fox, M.D.

Robert Fox, M.D.

One of the primary obstacles in developing treatments for MS is a lack of clinical understanding of the progressing form of the disease, said Robert Fox, M.D., staff neurologist at the Mellen Center for Multiple Sclerosis and professor of neurology at Cleveland Clinic Lerner College of Medicine.

“At the level of the biology, we don’t know what’s really driving that little-by-little progression. If we don’t know what’s causing it, it makes it really difficult to find a solution.”

About 85% of MS patients have the relapsing-remitting form of the disease, which is characterized by acute flares of symptoms followed by periods of stability. With relapsing MS, investigators conducting clinical trials can examine new lesions on an MRI and are able to conduct a six-month clinical observation to see if a potential therapy reduces lesions, Fox said. “If it does, we can move to a large phase 3 trial. The short MRI study helps us pick the drugs that are likely to be winners.”

But with progressive MS, “we don’t have a way to identify the most promising therapies for MS,” Fox noted. “We don’t know what biomarkers to use in that short proof-of-concept trial. That has made the development of new treatments much more difficult.”

Fox said the International Progressive MS Alliance has three main priorities to overcome some of the barriers. (He is chair of the Scientific Steering Committee.)

“The first is to understand, prevent, and reverse progression. These priorities are driving the research that seeks to answer the question of what is causing the progression, what biologic mechanisms are leading to it and what, therefore, might be leveraged to stop the progression,” Fox said.

Additionally, the Alliance aims to speed and improve clinical trials. “How can clinical trial methodologies be modified to make testing potential therapies more sensitive, more specific and more efficient so we can find therapies faster?” Fox said.

The Alliance also aims to improve well-being through proven therapeutic approaches, according to Fox. “Working to strategize ways to improve the quality of life of people living with progressive MS, the Alliance is bringing together the best and brightest minds in MS research,” he noted.

Ruth Ann Marrie, Ph.D.

Ruth Ann Marrie, Ph.D.

Some exciting new research trials should lead to better medicines and therapies for progressive MS, said Ruth Ann Marrie, Ph.D., professor of Medicine and Community Health Sciences at the University of Manitoba and director of the Multiple Sclerosis Clinic at Health Sciences Centre in Winnipeg.

For example, the ChariotMS trial in the United Kingdom is important because it is focused on people with more advanced progressive MS than the usual trial, Marrie told Managed Healthcare Executive®. “One of the big frustrations for people…is that those who are older or who have more significant impairments get excluded from clinical trials,” she said.

Marrie is also excited about the Improving Cognition in People With Progressive Multiple Sclerosis Using Aerobic Exercise and Cognitive Rehabilitation clinical trial, which is the first multinational rehabilitation trial in MS. In this trial, cognitive rehabilitation and aerobic exercise will be evaluated individually and in combinations to address cognitive dysfunction as the primary outcome variable.

Marrie said another notable trial is the ocrelizumab trial (ORATORIO-HAND). This trial will assess Genentech’s Ocrevus (ocrelizumab) in 1,000 patients with primary progressive multiple sclerosis including those later in their disease course and will assess improvement in hand function.

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