Treatment of progressive MS hits milestones in recent years: Review

Treatment options for progressive types of multiple sclerosis (MS) have expanded dramatically over the past decade, and several promising experimental therapies are in late stages of clinical development, a new review paper highlights.

The study, “Clinical trials for progressive multiple sclerosis: progress, new lessons learned, and remaining challenges,” was published in The Lancet Neurology.

MS has traditionally been divided into two broad categories: relapsing MS, marked by acute flares where symptoms worsen followed by periods of remission where symptoms ease, and progressive MS where symptoms continuously worsen over time.

In 2014, a team of researchers conducted a review of the scientific literature on progressive MS. At the time, dozens of clinical trials had been conducted in the preceding decades, but there weren’t any proven treatments for progressive MS types.

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Update on recent developments, future challenges in progressive MS field

Much has changed in the past 10 years, with multiple new trials completed or ongoing in the progressive MS field, so now the scientists reconvened to provide an update on where the field has come and challenges still to overcome.

The team specifically highlighted two treatments that came on the market in the last decade and have “had practice-changing positive results”: Ocrevus (ocrelizumab) and Mayzent (siponimod).

A Phase 3 trial called ORATORIO (NCT01194570) tested Ocrevus against a placebo in people with primary progressive MS, and results showed the therapy reduced the risk of disability progression. Similarly, the Phase 3 trial EXPAND (NCT01665144) showed treatment with Mayzent reduced the risk of disability worsening in people with secondary progressive MS.

Both Ocrevus and Mayzent work by reducing inflammation, and the researchers noted many participants in ORATORIO and EXPAND had signs of active brain inflammation upon entering the studies, which “is likely to have increased the proportion of participants who responded to therapy.”

“An important lesson from ORATORIO and EXPAND is that progressive multiple sclerosis could be [treatable with] immunomodulatory interventions in cohorts with relatively active disease and using responsive outcomes, if there is sufficiently long follow-up,” the researchers wrote.

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More than 10 clinical trials in Phase 3 testing of progressive MS treatments

Many ongoing clinical trials are testing potential new treatments for progressive MS, including more than 10 in Phase 3 testing. Some of the experimental treatments, such as Bruton’s tyrosine kinase inhibitors, are designed to reduce inflammation.

Other therapies in development are designed to promote neuroprotection — that is, reducing damage to nerve cells — while a third group work to promote the repair of myelin, the fatty sheath-like substance around nerve fibers that’s damaged in MS.

Though no therapy designed for myelin repair or neuroprotection has yet proven effective in people with MS, there are many promising candidates, and the researchers are optimistic such treatments could provide a critical tool to help limit MS progression and perhaps even reverse damage done by the disease.

The scientists noted a few important considerations for designing clinical trials to test these new approaches. For example, trials testing anti-inflammatory agents may have better response rates by enriching for patients with active inflammation, but on the other hand, neuroprotective or myelin-repairing therapies may show more dramatic effects in patients with little active inflammation.

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Clinical trials urged to include patients of diverse racial, ethnic backgrounds

The researchers also stressed trials should be designed to enroll people that are representative of the broader MS community, including patients of diverse racial and ethnic backgrounds as well as those with co-occurring health conditions.

Including patient-reported outcomes in trials can help provide valuable feedback from a patient perspective, the researchers noted, and increasingly innovative designs, such as studies testing multiple treatments at once, may allow studies to be done faster and more efficiently.

“Meaningful involvement of people affected by progressive multiple sclerosis is vital to maintain orientation to the issues that are most important to them,” the researchers wrote.

Overall, with many up-and-coming treatments, the researchers expressed optimism about further breakthroughs in the treatment of progressive MS in the coming years.