CAMBRIDGE, Mass.—October has been a busy month for Biogen, with data from research showing that serum neurofilament light (sNfL) is a potential biomarker of disease activity and treatment response in multiple sclerosis (MS) disease progression, which could provide physicians with real-world evidence to help inform treatment decisions.
As well, results from MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) are supporting the use of technology to monitor for clinically important outcomes, including cognitive changes. And new analyses of ongoing studies continue to support the long-term benefits of Tecfidera (dimethyl fumarate) and Tysabri (natalizumab), particularly when starting treatment early within the disease course. These findings were recently presented at the 34th Congress of the European Committee for Treatment and Research in MS (ECTRIMS) in Berlin.
Biogen is currently researching sNfL, a protein that is expressed in neurons and found in elevated levels in the blood of people with MS, as a biomarker of disease activity. Results from a retrospective analysis of more than 1,000 patients support the clinical relevance of sNfL levels in the blood to predict disease severity and monitor treatment response. Data indicate that sNfL levels above a certain threshold are associated with ongoing disease activity and negative clinical and radiologic outcomes, such as disability progression and brain atrophy. Researchers also found that introducing disease-modifying therapies significantly reduced sNfL levels, and greater reduction was associated with better treatment outcomes.
As Dr. Bernd C. Kieseier, head of the Global MS unit of Biogen, tells DDNews, “Biogen is actively collaborating with academic leaders in this field to better understand the clinical and research utility of this promising biomarker. There are currently no blood biomarkers for treatment monitoring in MS. The data presented at ECTRIMS support the clinical relevance of sNfL levels in the blood to predict disease severity and monitor treatment response in MS patients. Additional data presented at [ECTRIMS] add to our understanding of the temporal relationship between so called gadolinium-enhancing (Gd+) lesions on magnetic resonance imaging (MRI) of the brain and sNfL levels in MS patients, and suggest a complementary role to MRI in characterizing and monitoring the differential evolution of tissue injury in individuals with MS.”
Biogen has expanded its collaboration with Siemens Healthineers to develop an sNfL blood test as an additional tool to monitor MS. A highly sensitive, robust and validated assay will allow physicians to measure sNfL levels in the blood of MS patients with the goal of better understanding disease activity and monitoring treatment response.
Dr. Peter Calabresi, director of the Division of Neuroimmunology and Neuro-infectious Diseases at the Johns Hopkins University School of Medicine, said, “These findings support sNfL as a clinically useful biomarker to help predict whether a person with MS is likely to have a fast-progressing or milder disease course. They also open the possibility of using a simple blood test to monitor whether a patient is responding to a specific treatment. The strong predictive power of sNfL may ultimately provide physicians with additional information beyond what is currently measured by MRIs to help guide treatment decisions.”
On the technological side of things, the MS PATHS collaboration of 10 leading MS centers in Europe and the United States, along with Biogen, uses technology in routine care to collect clinical, MRI and biologic data from patients in real time at the point of care. Using an iPad-based assessment, researchers are able to broadly monitor for changes in motor, visual and cognitive function.
Cognitive deficits affect over half of people living with MS, but aren’t regularly assessed in clinical practice and can be difficult to quantify. “New MS PATHS data presented at ECTRIMS demonstrate that cognitive decline is as prevalent as physical decline in people with MS, but can occur independently from physical symptoms,” notes Kieseier. “In fact, cognitive decline occurred independently from physical symptoms in approximately 75 percent of patients in the study. These results underscore the importance of monitoring cognition in routine care and the need for effective treatment strategies for cognitive changes in MS.”
To help physicians outside of the MS PATHS network easily assess cognition in their patients, Biogen has developed CogEval, a free app available to healthcare providers in the United States, Europe, Canada, Japan, Australia and New Zealand. Like the Processing Speed Test used in MS PATHS, CogEval is modeled after and validated against the Symbol Digit Modalities Test, regarded by many experts as the gold standard of MS cognitive screening tests.
CogEval provides an iPad-based assessment of cognitive function that, according to Kieseier, “evaluates cognitive function using elements of attention, psychomotor speed, visual processing and working memory. During the two-minute assessment, the patient pairs abstract symbols with numbers, using a key as a guide. CogEval can be used by MS specialists anywhere at any time.”
Finally, results from the ENDORSE study demonstrate that the clinical benefits of Tecfidera in reducing MS relapses and disability progression in newly diagnosed patients were maintained throughout nine years of continuous Tecfidera treatment, with relapse rates remaining low and more than 90 percent of patients maintaining walking abilities. Analysis from the Tysabri Observational Program (TOP), the largest ongoing real-world study of Tysabri-treated patients, reinforces the long-term safety and consistent effectiveness of Tysabri over 10 years, especially for patients with minimal or mild disability and those who were previously treated with fewer disease-modifying therapies.
“Research shows that introducing disease-modifying therapies significantly reduces sNfL levels,” says Kieseier. “In the retrospective analysis, researchers found that sNfL levels were significantly lower in patients taking Plegridy or Tysabri compared to those taking placebo, with the most pronounced effects observed with Tysabri. Treatment with Tysabri reduced sNfL levels below the identified threshold in 96 percent of patients.
“The research we presented at ECTRIMS not only reflects our proven record of developing innovative medicines for MS, but also our pursuit of new clinical avenues aimed at generating data that we believe will lead to greater precision medicine in MS. New analyses of ongoing studies presented at ECTRIMS continue to support the long-term efficacy and well-characterized safety of Tecfidera and Tysabri, particularly when used early within the disease course.”