Breakthrough Treatment Offers Hope for Progressive Multiple Sclerosis
A groundbreaking study, published in the New England Journal of Medicine and led by Dr. Jiwon Oh, a neurologist and scientist at St. Michael’s Hospital, part of Unity Health Toronto, reveals that a new drug, Tolebrutinib, could slow disability progression in people with non-relapsing progressive multiple sclerosis (MS). This subtype of MS has historically been challenging to treat, as it does not respond well to existing therapies.
A New Class of Treatment
Tolebrutinib is part of an innovative class of drugs called Bruton’s tyrosine kinase (BTK) inhibitors. It works by targeting the BTK enzyme to reduce the activity of B cells, which contribute to inflammation in the brain and spinal cord in MS. Additionally, Tolebrutinib may influence microglia, immune cells linked to MS progression, offering a novel approach to managing the disease.
Key Findings from the Study
Dr. Oh’s research compared Tolebrutinib to Teriflunomide, a standard MS treatment, in patients with relapsing MS, the most common form of the disease. The study, which included two phase-three trials (GEMINI I and II), found that both drugs similarly reduced the annualized relapse rate (ARR), the average number of relapses per year. However, Tolebrutinib stood out by significantly reducing disability progression, even in patients with relapsing MS, suggesting it targets the underlying mechanisms of progressive disease.
These results build on findings from the HERCULES trial, which showed Tolebrutinib reduced disability progression in non-relapsing secondary progressive MS compared to a placebo. “This highlights that Tolebrutinib is addressing progressive disease processes, even in patients who experience relapses,” said Dr. Oh, who also serves as the Medical Director of the BARLO MS Program and holds The Waugh Family Chair in Multiple Sclerosis Research.
Why This Matters
Progressive MS, unlike relapsing MS, involves a slow, steady decline in neurological function without clear relapses, making it difficult to treat with existing therapies. Dr. Oh emphasized the urgent need for effective treatments: “While there are many options for relapsing MS, they have limited impact on progressive disease. Tolebrutinib’s ability to target processes in the brain driving progression is a significant step forward.”
The study’s results are particularly encouraging following disappointing outcomes from another BTK inhibitor, which showed no effect on relapses or progression. “I was cautiously optimistic, but these findings are a relief and a source of hope,” Dr. Oh shared. “For patients with progressive MS, this could mark the beginning of a new era in treatment.”
What’s Next?
The next step is to seek regulatory approval from agencies like the FDA, Health Canada, and the European Medicines Agency. Once approved, Tolebrutinib could benefit a broad range of MS patients, including those with other forms of the disease who experience progression. Patients starting the treatment will require regular monitoring, particularly for rare cases of liver enzyme elevation, which can be managed with routine blood tests.
A Promising Future
Dr. Oh reflected on the progress in MS treatment: “Thirty years ago, the first therapies for relapsing MS reduced relapses by about 30%. Today, we’re seeing up to 90% efficacy. This 30% reduction in disability progression with Tolebrutinib is a similar starting point for progressive MS, and I’m hopeful about where we can go from here.”
For the MS community, Tolebrutinib represents a beacon of hope, offering a potential new tool to slow the devastating effects of progressive MS and improve quality of life.
