Our Relentless Pursuit for New Ways to Address Disability Progression in Multiple Sclerosis

While existing therapies can effectively manage MS relapses, there is still a need to address this persistent worsening of disability that occurs independent of relapses.³ That’s why Sanofi is focused on identifying and targeting smoldering-associated worsening (SAW) in MS. SAW characterizes the biology of chronic neuroinflammation, often subtle and gradual, which remains untreated by current therapeutic options. Over time, multiple sclerosis slowly shifts from relapsing to progressive and the clinical features of SAW start to emerge, leaving a significant unmet need in the MS community.⁴

Cyril, a 55-year-old in France, has been living with MS for 15 years, and SPMS for the past 5 years.

“My MS has been recurring and intermittent. But after several flare ups, there started to be marked decline. I had plenty of markers. Things I used to do that I can’t anymore like being able to walk a kilometer. Now I can only walk 300 meters. No longer can I walk or ride bikes with my children when on vacation. That’s my progression.”

“Learn, fight, and improve.” This is the determined mindset Cyril has adopted about his MS today, and as he looks ahead to his and his family’s future together.

Cyril’s story is unfortunately not uncommon. For many people with MS, relapses may be non-existent, but subtle progression continues. This worsening of disease may lead to long-term impacts on cognition, movement, well-being, and independence.⁵

Additional survey results from IMSS revealed that the invisible symptoms such as fatigue, cognitive impairment and sensory issues are among the most debilitating for people with MS. The survey findings illustrate how living with MS can also lead to significant disruptions in a person’s career.¹

MS is one disease, but it’s not easily defined with clear-cut types. It’s more like a spectrum of disease. People can experience a mix of disability symptoms and progression patterns that don’t always fit neatly into diagnostic boxes. Following a diagnosis, most people have or develop the relapsing remitting type of disease.⁶ Over time the disease may worsen into secondary progressive MS.⁷

“It’s because of the success of disease-modifying therapies in MS that a puzzling question arose: If someone with MS is relapse-free, why then would they experience disability progression?” said Luis Felipe Orozco, MD, PhD, Sanofi’s Global Medical Head of Neurology. “The answer to this troubling question lies in chronic or persistent neuroinflammation, a key target of our neurology pipeline as we seek to develop therapies to address the pathological processes driving MS disability distinct from relapses.” 

The latest research shows that there are two processes happening in MS from the very start of disease. The acute process that causes relapses and MRI activity, and the newly understood chronic smoldering process which leads to physical and cognitive changes from persistent inflammation. The smoldering process represents a new era in neurological research, providing better insights into the central nervous system and the mechanisms of the immune system.⁴ 

This new way of thinking about MS is opening up unexplored avenues to address unmet needs, including research into new ways to measure disability progression and innovative approaches for developing different kinds of treatments for people living with the disease.⁴

“Working alongside people with MS, their families and the clinicians, we are on an important journey to determine the right ways of characterizing disability progression so we can more accurately measure and treat it,” added Sanofi’s Orozco.

Currently, there are no available treatments approved to address smoldering-associated worsening in MS. This “smoldering disease” causes symptoms that may be distinct from the acute symptoms associated with relapses. While not acute, these symptoms do accumulate over time and produce disability accumulation or build-up. Few methods exist to quantify these symptoms and how they progress in people living with MS. The typical instruments used in clinics today to measure disease activity, such as MRI scans, are not the right ones to capture all of the components of disability progression, including subtle changes in how a person speaks, feelings of fatigue or ability to do daily activities.⁴

We recognize the need to better measure the full range of symptoms that can quietly erode quality of life – even when relapses are under control and MRIs appear clean. We have recalibrated our research to address these needs, given the potential to positively alter people’s lives.

Through our research, we are helping people with MS live for the moment, not for the disease.