#MSParis2017 – Progressive MS Research Among ECTRIMS Highlights, National MS Society Says

The 7th Joint ECTRIMS-ACTRIMS Meeting, taking place in Paris this month, is one of the largest scientific conferences focused solely on multiple sclerosis (MS), and the National Multiple Sclerosis Society will be among the many interested parties attending.

To get a feeling for meeting highlights and presentations the society will follow most closely, Multiple Sclerosis News Today spoke to Bruce Bebo, executive vice president for research at the National MS Society.

Fresh information on outcomes in recent scientific studies, Bebo said, “is an incredibly important activity to advance progress in MS research and MS care.”

The joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) runs Oct. 25–28.

Progressive MS research in the spotlight

While information on more than 5,000 ECTRIMS presentations was only released this week, Bebo appeared to have his focus set — progressive MS.

“I think the presentation I’m most excited about is the reporting of results from the SPRINT-MS trial,” he said. The Phase 2 study (NCT01982942) — partly sponsored by the National MS Society — explored MediciNova’s ibudilast in people with both primary and secondary progressive MS.

With the trial recently completed, researchers will present data on how the drug managed to impact brain tissue loss and other disease parameters.

Also on Bebo’s list is a presentation by lead investigators of the Global Collaborative Network of the International Progressive MS Alliance.

The alliance, which has been around for three or four years, has been instrumental in advancing progressive MS research, “identifying critical questions that need to be answered to make progress in treatment of progressive MS. We’ll hear from investigators trying to answer those key questions,” Bebo said, highlighting three network projects.

One focuses on identifying targets and treatments that might have a neuroprotective effect or may modulate innate immune system processes inside the nervous system to slow or stop progression in this type of MS.

A second project aims to identify new repair pathways, and the third to identify patterns in magnetic resonance imaging (MRI) scans that might differentiate those most likely to respond to a progressive MS treatment from those who are not.

If successful, such scans could speed trials of progressive MS therapies, Bebo said.

“One of the major roadblocks for the development of progressive MS treatments is the lack of a quick outcome measure that can determine whether a person is responding to treatment or not,” he said, because researchers now lack a good way to measure MS disease progression.

As progression is often slow and spread over time, trials exploring progressive MS treatments are currently lengthy, time-consuming and expensive.

Another reason research in progressive MS lags behind relapsing MS is a lack of understanding of the biological processes that cause progression, he said.

But advances in recent years are closing this knowledge gap.

“That’s changing rapidly, and there are more targets being identified for treatment for progressive MS that I can remember ever having before. Some of these targets are being translated into clinical trials now,” Bebo said.

“My impression from reading the abstracts for this meeting and the last few meetings is that there’s tremendous attention being paid to progressive MS, more than at any time that I can remember,” he added. He credits the International Progressive MS Alliance for increasing awareness of progressive MS — an awareness that has led to way a better disease understanding and greater development efforts.

Regeneration advances

With disease progression —in both relapsing and progressive MS — comes disability accumulation. And while efforts to slow disability are increasingly successful, no one so far has succeeded in developing a therapy that regenerates damaged myelin and repair neurons.

But Bebo is optimistic that a breakthrough may be around the corner.

“The area of myelin repair, particularly, has seen a tremendous amount of activity and a tremendous advance in our knowledge of levers that we can use to promote myelin repair,” he said, explaining that only a few years back, no one even knew that oligodendrocyte progenitor cells (OPCs) — precursor to myelin-producing cells — existed in our brains.

Now scientists know that these cells not only exist, but are the most abundant dividing cells in the central nervous system — knowledge that opens the possibility of learning to harness their power.

In early MS stages, Bebo said, it appears these cells retain their regenerative capacity. But as disease progresses, this ability is lost. Studies of factors that promote or prevent OPCs from maturing into myelin-producing cells may lead researchers to compounds that could tip the balance toward repair. There is a growing number of drug targets, Bebo added.

For instance, new studies of a blocker of LINGO-1 by Biogen are ongoing, he said, and other presentations focus on selective estrogen receptor modulators that promote myelin repair, and the role of a muscarinic receptor in blocking repair.

In addition, researchers believe a compound called ABT-555, developed by AbbVie, has the potential to regenerate axons and promote myelin repair. It was recently shown be safe in a Phase 1 study, Bebo said.

“So I’m looking forward to hearing more about outcomes from that trial,” he said, “whether there might be any hints for effectiveness.”

Beyond progressing disease

The meeting also offers plenty of fresh information on already approved approaches.

“Every year, we learn a little bit more about how some of the newer, and even some of the older, treatments perform when used in the real world,” said Bebo, looking forward to data from extension trials and new analyses.

Among these presentations are updates on the effectiveness and safety of Ocrevus (ocrelizumab) — a Genentech therapy that continues to elicit interest among patients and neurologists.

The fact that Ocrevus — which targets B-cells — was found effective in both primary progressive MS (PPMS) and relapsing patients has spurred a wave of research into B-cell therapies.

“Ocrevus clinical trials showed to the scientific community that B-cells are really important in relapsing MS and in progressive MS. So there are a number of ‘follow-on,’ or B-cell, approaches that may have advantages over current approaches that are being tested,” Bebo said.

In addition, there’s advances in treatments that do not require injections. Mavenclad (cladribine tablets), developed by Merck KGaA, was recently approved in Europe as an effective relapsing-remitting MS therapy, and researchers will share additional data at the meeting.

Another compound that Bebo keeps his eyes on is Novartis’ siponimod — an agent similar to Gilenya (fingolimod) — but with a better safety profile. At last year’s ECTRIMS meeting, siponimod was shown to be effective in secondary progressive MS, Bebo said.

“So I’m looking forward to seeing what else we’ve learned in the last year about siponimod, and looking to see where we are in getting that agent approved for treatment.”

Over the past years, researchers have also looked into the effects of drugs — intended for other conditions — as potential MS therapies. Dietary supplements, likewise, are attracting some attention — perhaps most prominently illustrated by MedDay’s trial of biotin for progressive MS.

Bebo points to several other noteworthy compounds in this category. “One is called lipoic acid, it’s an antioxidant, it’s something you can get over-the-counter in a health foods store,” he said.

At ECTRIMS 2016, he added, researchers presented rather remarkable findings that the supplement potently reduced brain tissue loss —  a loss they believe signals disease progression.

New data on lipoic acid — now in a society-supported Phase 2 trial (NCT03161028) in progressive MS — will be shared at the meeting. And updates on the use of statins — cholesterol-lowering drugs that have been shown to slow brain shrinkage in MS — are also on Bebo’s list.

Patient-centered outcomes

With so much focus on research and drug development, we wondered if there was room for the patient perspective at such a large gathering.

“My impression is that the patient perspective on the effectiveness and side effects and risks of these disease-modifying therapies is something that is getting more and more attention at every one of these meetings,” said Bebo.

Plenty of patient-centered outcome measures are being evaluated in clinical trials, and researchers will address how they performed.

“It’s incredibly important a piece of evidence that regulators need in order to evaluate the approval of a treatment,” Bebo said. “And certainly, that is the kind of information that’s incredibly valuable to learning how an agent is performing in the real world and how one can improve outcomes for people with MS.”

Patients, after all, best understand whether and how a treatment is working — and can help to guide research efforts into new ways of treating their disease.