The changing multiple sclerosis landscape: Earlier diagnosis, improved monitoring, and a more competitive race for durable disease control

Multiple sclerosis (MS) is undergoing a meaningful evolution in how it is understood, diagnosed, and managed. Advances in diagnostic criteria, the growing use of biomarkers, and an increasingly competitive therapeutic landscape are collectively shifting the field towards earlier identification and more proactive, biology-led disease control.

Rather than being defined primarily by relapses and overt clinical symptoms, MS is now increasingly approached as a condition that can be detected, monitored, and treated across its underlying biological course. This transition is raising expectations for both clinical practice and treatment development, with greater emphasis on delaying progression, preserving function, and delivering long-term outcomes that matter to patients.

At the American Academy of Neurology (AAN) 2026 Annual Meeting, MS saw several significant updates, with three key themes emerging: earlier diagnosis through more biologically anchored criteria, broader use of biomarkers to monitor disease activity and progression, and a more competitive treatment landscape in which efficacy, convenience, disability outcomes, and lifecycle strategy are all starting to matter more.

Together, these core areas of focus signal a significant shift within the MS space, reflecting a gradual move away from viewing MS primarily as a disease that becomes visible only once classical symptoms emerge, and towards one that can be identified, monitored, and treated earlier in its biological course. As diagnostics broaden and monitoring becomes more sensitive, this shift is expected to expand the addressable treated population, reshape treatment sequencing strategies, and raise the evidentiary threshold for differentiation, ultimately improving long-term patient outcomes.

Earlier identification and upstream diagnosis

The revised 2024 McDonald criteria, an updated framework for diagnosing MS with the intention of enabling earlier and more accurate diagnosis, were a particular focus at this year's congress. Discussion centred on how the updated criteria broaden the diagnostic framework by allowing the optic nerve to count as a fifth anatomical location for demonstrating dissemination in space, alongside the incorporation of newer supportive tools, including the central vein sign, paramagnetic rim lesions, and cerebrospinal fluid kappa free-light chains. The criteria also move towards a more unified approach across relapsing and progressive disease, and towards diagnosis in a broader set of clinical presentations than before.

Clinically, this could enable earlier diagnosis without abandoning specificity. This is particularly important, as earlier diagnosis widens the opportunity to introduce high-efficacy treatment before disability accumulates, strengthens the rationale for biomarker-based monitoring, and may ultimately increase the number of patients considered appropriate for earlier intervention. The caveat is that implementation will matter: some of the new tools require specialist imaging or lab capabilities, so uptake is unlikely to be uniform across centres or geographies.

Fenebrutinib demonstrates significant clinical potential

On the therapeutic side, Roche reported positive Phase III FENhance 1 and 2 results in relapsing MS, showing superiority over teriflunomide on annualised relapse rate over 96 weeks. Annualised relapse rate (ARR) was reduced by 51.1% in FENhance 1 and 58.5% in FENhance 2, with large reductions in MRI activity as well: new T1 gadolinium-enhancing lesions fell by 70.7% and 77.6%, while new or enlarging T2 lesions fell by 76.0% and 82.5%, respectively. Positive trends were also reported on composite confirmed disability progression, with a data package now expected to be submitted to regulators for both relapsing and PPMS.

This data matters beyond the immediate efficacy story because they materially change the BTK inhibitor narrative in MS. After years of interest in the class, the question has shifted from theoretical promise to whether any BTK inhibitor can deliver a sufficiently differentiated efficacy and safety profile to secure a durable place in practice. Based on Roche’s framing, fenebrutinib is being positioned not simply as another oral option, but as a potential first-in-class, high-efficacy oral spanning relapsing and progressive biology. If regulators accept that broader positioning, fenebrutinib could become one of the most commercially important launches in the category’s next phase.

Roche continues to promote Ocrevus

Fenebrutinib was not the only clinical showpiece at this year’s congress, with more established anti-CD20 therapies also picking up significant interest. In Roche’s ORATORIO-HAND, a broader PPMS population that included older patients and those with more advanced disability, ocrelizumab was shown to reduce the risk of 12-week composite confirmed disability progression by 30% versus placebo, with sustained progression of 32.7% versus 40.4%. The effect was particularly notable on upper-limb disability, with 16.7% versus 24.9% progressing on the 9-Hole Peg Test, and in the MRI-active subset the risk reduction reached 55%.

Roche also presented paediatric data in OPERETTA 2. In 187 patients aged 10 to 17 years with paediatric-onset MS, ocrelizumab was non-inferior to fingolimod on relapse control, with a rate ratio of 0.52, and was superior on MRI endpoints, reducing new or enlarging T2 lesions with a rate ratio of 0.52 and T1 gadolinium-enhancing lesions at week 12 with a rate ratio of 0.13. No adverse events led to ocrelizumab withdrawal.

Competition inside the anti-CD20 class is becoming more nuanced

Yet, AAN 2026 also made clear that anti-CD20 competition is becoming more nuanced, with TG Therapeutics using AAN 2026 to reinforce BRIUMVI’s positioning through real-world and switch data, emphasising both disease control and treatment experience. In the Phase IV ENABLE study, on-treatment annualised relapse rate was 0.012 across 342.9 patient-years, and 99.5% of evaluable patients reported no relapses while on ublituximab. Infusion-related reactions were most common at first infusion, affecting 18.0% of participants, but all were grade 1 or 2 and resolved completely. Median infusion duration fell from 247 minutes for the first infusion to 63 minutes for subsequent infusions.

The clinical significance of those data is limited by the absence of a randomised comparator, but the commercial relevance is more straightforward. In a maturing anti-CD20 class, operational factors increasingly matter: infusion time, tolerability, site-of-care burden, and patient willingness to stay on treatment all shape real-world adoption. ENABLE does not rewrite the efficacy hierarchy, but it does support a positioning narrative in which BRIUMVI competes on practicality as well as potency.

That same theme appeared in TG’s ENHANCE dataset, which looked at patients switching from ocrelizumab to ublituximab. Ninety-two percent of 600 mg infusions were completed without interruption or slowing, and the study reported a 69.0% reduction in “wearing-off” at week 24 and a 73.3% reduction at week 48 among participants who had previously reported that effect. Again, this is not a head-to-head efficacy challenge to Ocrevus. But it is a reminder that the next commercial battleground in MS may be decided partly by patient experience and service model, not just by annualiwsed relapse rate.

Biomarkers are operational tools

Another important theme was biomarker-led monitoring. Real-world use of Octave’s MSDA blood test was presented as having expanded substantially since launch, with more than 25,000 tests administered to nearly 18,000 people with MS by the end of January, ordered by more than 400 providers across 237 institutions and 41 states. Across US orders, 63.9% were for routine monitoring and 29.3% for initial assessment. At UT Southwestern, the test was described as serving multiple clinical roles, including risk stratification at diagnosis, relapse confirmation, ongoing monitoring, and use as an alternative to more expensive or less accessible MRI in some scenarios.

The bigger signal is not that any one blood test has already become standard of care, but that the market is moving in that direction. The language used around MSDA at AAN reflected a broader ambition to reduce dependence on episodic imaging and move towards a more biologically grounded, longitudinal model of disease surveillance. That is clinically attractive in a disease where subclinical activity and progression remain difficult to capture early. Commercially, it could create space for diagnostics companies, reshape evidence generation in drug development, and raise expectations that therapies demonstrate benefit not only on relapse and MRI lesions, but on broader measures of disease biology over time.

Smaller programmes still have room, but the bar is rising

GA Depot generated a statistically significant post hoc signal on EDSS stability at one year, with 96.4% of treated patients showing no EDSS increase versus 91.6% on placebo. That is a modest dataset compared with the larger competitive stories at the meeting, but it still fits the same overarching trend: MS is increasingly being framed around preserving function and stabilising disability earlier, rather than reacting only to overt inflammatory events.

The commercial challenge for programmes like GA Depot is that the bar is rising. Convenience still matters, and established mechanisms can still carve out roles in selected patient segments, particularly where tolerability, familiarity, or adherence are important. But the overall market is moving toward higher efficacy, earlier use, and richer biological monitoring. In that environment, lifecycle plays will need a sharper positioning story to remain relevant.

What’s next

The larger conclusion from AAN 2026 is that multiple sclerosis is moving from an inflammation-led market to a broader disease-control market. Relapse suppression still matters, but it is no longer enough on its own to define leadership. The next winners are likely to be the companies that can align with a more biology-led model of care: diagnosing earlier, monitoring more continuously, and demonstrating value on progression, function, convenience, and real-world treatment fit as well as traditional inflammatory endpoints.

About the authors

Ivo Carre, PhD, is a senior business analyst at Lifescience Dynamics in London, with a doctorate in Neuroscience from the UKDRI and over two years of biopharma consulting experience. He has supported various clients across several indications, including oncology, neurology, and rare diseases, with expertise in competitive intelligence, market research, and market access.

Rachele Saccon, PhD, is a senior business analyst at Lifescience Dynamics. She has supported and managed multiple projects in CI, but also competitive simulation, MA, and MR. She supported workstreams across many different therapeutic areas (at both global and regional levels), as well as deep-dives, sales force analysis, and conference. She also successfully lead projects of a strategic nature, mapping areas for investment, prioritising promising technologies and assessing potential partners. Saccon has extensive research and development experience in neuroscience and genetics. Prior to joining Lifescience Dynamics, she worked as a post-doctoral researcher at UCL where she managed projects in the field of ALS and Down Syndrome. Saccon holds a PhD in Genetic and Neuroscience from University College London and an MSc in Evolutionary Biology from the University of Padua, Italy.