Multiple Sclerosis Clinical Trials 2026 — 300 Active Studies, 32 Phase 3 Programs

MS Phase 3 Pipeline — Recruiting & Active Programs (2026)

The following table summarizes Phase 3 multiple sclerosis programs currently active or recruiting on ClinicalTrials.gov. Programs are grouped by mechanism class.

Drug / Sponsor	Mechanism	Subtype	Trial ID	Status
Tolebrutinib Sanofi	BTK inhibitor	RRMS	NCT06141473	Recruiting
Tolebrutinib Sanofi	BTK inhibitor	Non-relapsing progressive MS	NCT06141486	Recruiting
Fenebrutinib Hoffmann-La Roche	BTK inhibitor	RRMS vs teriflunomide (FENopta 1)	NCT04586023	Active, NR
Fenebrutinib Hoffmann-La Roche	BTK inhibitor	RRMS vs teriflunomide (FENopta 2)	NCT04586010	Active, NR
Remibrutinib Novartis	BTK inhibitor	RRMS vs teriflunomide	NCT05156281 / NCT05147220	Active, NR
Remibrutinib Novartis	BTK inhibitor	Secondary progressive MS	NCT07225504	Recruiting
Orelabrutinib Zenas BioPharma	BTK inhibitor	Secondary progressive MS	NCT07299019	Recruiting
Ocrelizumab Hoffmann-La Roche	Anti-CD20 (mAb)	PPMS, RRMS (multiple extensions + dose studies)	NCT04035005, NCT04544436, NCT05123703	Active, NR
Ublituximab TG Therapeutics	Anti-CD20 (mAb)	RMS — extension & PK studies	NCT04130997, NCT07211633	Active / Recruiting
ABP 692 (ocrelizumab biosimilar) Amgen	Anti-CD20 biosimilar	RRMS	NCT06700343	Recruiting
Ocrelizumab biosimilar Sandoz	Anti-CD20 biosimilar	RRMS	NCT06847724	Recruiting
Frexalimab (SAR441344) Sanofi	Anti-CD40L (CD40 ligand)	RRMS (Phase 3 RRMS)	NCT06141473	Recruiting
Frexalimab (SAR441344) Sanofi	Anti-CD40L (CD40 ligand)	Non-relapsing progressive MS	NCT06141486	Recruiting
IMU-838 (vidofludimus calcium) Immunic AG	DHODH inhibitor	RRMS	NCT05134441, NCT05201638	Active, NR
Ozanimod Bristol-Myers Squibb (Celgene)	S1P1/5 modulator	RRMS vs fingolimod	NCT06408259	Recruiting
HSCT vs. best available therapy NIAID	Hematopoietic stem cell transplant	Relapsing MS (refractory)	NCT04047628	Recruiting

The BTK Inhibitor Race — The Biggest Story in MS Right Now

The most important competitive dynamic in the MS pipeline is the four-way BTK inhibitor race. BTK (Bruton's tyrosine kinase) is expressed in both B cells and microglia — giving BTK inhibitors a theoretical advantage over anti-CD20 therapies, which deplete peripheral B cells but don't cross the blood-brain barrier. The rationale: targeting CNS-resident microglia could slow progression independent of relapses.

Tolebrutinib (Sanofi) — First BTK Inhibitor Approved in MS

Tolebrutinib became the first BTK inhibitor approved for any MS indication when the FDA cleared it in June 2025 for non-relapsing secondary progressive MS (nrSPMS), based on the positive HERCULES Phase 3 trial. This is a landmark for progressive MS — a subtype with no approved high-efficacy options prior to this approval. Sanofi now has tolebrutinib in additional Phase 3 trials for relapsing MS and non-relapsing progressive MS (NCT06141473, NCT06141486).

Key competitive advantage claim: brain penetration. Unlike ocrelizumab, tolebrutinib reaches CNS-resident microglia — which may drive progression even when peripheral inflammation is controlled.

Fenebrutinib (Hoffmann-La Roche) — FENopta 1 & 2

Roche has two identical Phase 3 trials (FENopta 1: NCT04586023; FENopta 2: NCT04586010) comparing fenebrutinib against teriflunomide in relapsing MS. Both are active but no longer recruiting, suggesting enrollment is complete with readouts anticipated. Fenebrutinib is designed to be highly selective and brain-penetrant. It does not covalently bind C481 on BTK — potentially relevant if resistance patterns emerge.

Remibrutinib (Novartis) — RRMS and Progressive MS

Novartis has expanded its remibrutinib Phase 3 program to include both RRMS (NCT05156281, NCT05147220 — active, not recruiting) and a new trial in secondary progressive MS (NCT07225504 — recruiting). The SPMS expansion directly chases the niche opened by tolebrutinib's approval in nrSPMS. Novartis is the only company with a single BTK inhibitor across both relapsing and progressive MS Phase 3 programs.

Orelabrutinib (Zenas BioPharma / BeiGene)

Orelabrutinib, a BTK inhibitor originally developed by BeiGene for B-cell malignancies and licensed to Zenas BioPharma for autoimmune indications, has entered Phase 3 in secondary progressive MS (NCT07299019, recruiting). This is an early-stage competitor — meaningful for BD teams monitoring the progressive MS landscape but likely 3–5 years from potential approval.

What happened to evobrutinib (Merck)?

Merck terminated its evobrutinib Phase 3 program in 2023 after both RRMS trials (evolutionRMS 1 and 2) failed to meet their primary endpoints versus teriflunomide on annualized relapse rate. The evobrutinib failure raised questions about the BTK class — but tolebrutinib's HERCULES success in progressive MS suggests disease subtype and target CNS penetration are the differentiating factors, not the class itself.

Anti-CD20 Dominance — and the Biosimilar Reckoning

Anti-CD20 B-cell depletion remains the backbone of high-efficacy MS therapy. Ocrelizumab (Roche, Ocrevus) has been the market leader since its 2017 approval in RRMS and PPMS, generating over $7B/year at peak. Ublituximab (TG Therapeutics, Briumvi) entered the RRMS market in 2023 with a shorter infusion time as its differentiation claim.

Ocrelizumab extensions and dose optimization

Roche has multiple active Phase 3 trials extending the ocrelizumab program: a higher-dose study (NCT04544436), a PPMS long-term extension (NCT04035005), and a comparison against fingolimod in RRMS (NCT05123703). These studies support label expansion and post-marketing commitments rather than representing new clinical needs.

Ocrelizumab biosimilars entering Phase 3

The first ocrelizumab biosimilars have reached Phase 3 clinical trials:

• Amgen ABP 692 vs. Ocrevus (NCT06700343) — comparative PK/PD/efficacy/safety in relapsing-remitting MS. Recruiting.
• Sandoz ocrelizumab biosimilar vs. Ocrevus (NCT06847724) — similar design. Recruiting.

Ocrelizumab's U.S. patent situation will determine when biosimilars can launch commercially. BD and strategy teams at Roche and ublituximab-holder TG Therapeutics are tracking biosimilar timelines closely.

Progressive MS — The Harder Frontier

Secondary progressive MS (SPMS) and primary progressive MS (PPMS) have historically been poorly served by DMTs. The mechanisms driving progression — neurodegeneration, CNS-resident microglial activation — are partly independent of peripheral inflammation. This is why the anti-CD20s, which deplete circulating B cells, have limited efficacy once progression predominates.

Roche PPMS extensions

Ocrelizumab remains the only approved therapy for PPMS. Roche's Phase 3 extensions (NCT04035005, NCT05269004) are long-term safety and efficacy studies in progressive subtypes rather than new programs.

BTK inhibitors in progressive MS — the rationale

The brain-penetrance rationale for BTK inhibitors is most compelling in progressive MS. Microglial activation persists in progressive patients regardless of peripheral inflammatory control. Tolebrutinib's approval in nrSPMS — a subtype with no prior high-efficacy DMT — is the proof-of-concept for this mechanism. Three additional BTK inhibitor programs are now pursuing progressive subtypes: remibrutinib in SPMS (Novartis, NCT07225504), orelabrutinib in SPMS (Zenas, NCT07299019), and tolebrutinib's ongoing non-relapsing progressive MS trial (Sanofi, NCT06141486).

Novel Mechanisms — Frexalimab and Vidofludimus

Frexalimab (Sanofi) — Anti-CD40L, Phase 3

Frexalimab (SAR441344) is a novel anti-CD40 ligand antibody that prevents CD40–CD40L interactions — disrupting both T-cell and B-cell activation simultaneously. The mechanism is conceptually distinct from anti-CD20 (which only depletes B cells) and BTK inhibitors (which block B-cell and microglial signaling). Sanofi's Phase 2 RRMS trial showed strong efficacy signals in 2024, prompting rapid Phase 3 initiation. Two Phase 3 trials are now recruiting:

• NCT06141473 — RRMS, pivotal Phase 3 (recruiting)
• NCT06141486 — Non-relapsing progressive MS (recruiting)
• NCT07325292 — SC vs. IV route comparison (recruiting)

If frexalimab's Phase 3 succeeds, Sanofi would have both a BTK inhibitor (tolebrutinib, approved) and an anti-CD40L (frexalimab, Phase 3) — two mechanistically distinct high-efficacy agents in MS. A significant pipeline position.

Vidofludimus calcium (IMU-838, Immunic AG) — DHODH inhibition

Vidofludimus calcium is an oral selective DHODH (dihydroorotate dehydrogenase) inhibitor that suppresses activated immune cells. Unlike standard DMTs, its proposed mechanism involves selective suppression of rapidly proliferating lymphocytes without systemic immunosuppression. Immunic AG has two Phase 3 RRMS trials (NCT05134441, NCT05201638) — both active but no longer recruiting, suggesting enrollment is complete.

HSCT for Refractory Relapsing MS

The NIAID-sponsored Phase 3 trial (NCT04047628) comparing autologous hematopoietic stem cell transplantation (HSCT) against best available therapy in refractory relapsing MS continues to recruit. HSCT has shown impressive long-term remission data in single-arm studies and small trials; this Phase 3 head-to-head comparison is the definitive test. The trial is targeting highly active RRMS patients who have failed multiple DMTs — a population for whom available options are limited.

What DataLookout monitors for multiple sclerosis

DataLookout pulls directly from the ClinicalTrials.gov API every day. For an MS watch profile, you can configure:

• Condition keywords: "multiple sclerosis", "RRMS", "relapsing-remitting MS", "primary progressive MS", "PPMS", "secondary progressive MS", "SPMS", "clinically isolated syndrome", "progressive MS"
• Mechanism keywords: "BTK inhibitor", "anti-CD20", "S1P modulator", "HSCT", "stem cell", "remyelination", "anti-CD40L", "DHODH"
• Phase filter: Phase 2 proof-of-concept, Phase 3 pivotal, or all phases
• Sponsor filter: Industry-sponsored only (for competitive intelligence), or all sponsors including NIH and academic centers
• Status filter: Recruiting only, active (including active not recruiting), or all status types

Who uses multiple sclerosis trial monitoring

Neurology pharma BD and strategy teams

BD teams at CNS-focused pharmaceutical companies track the MS pipeline to identify licensing and acquisition targets, anticipate competitive launches, and inform pipeline strategy. The BTK inhibitor race is shaping BD decisions now: companies without a CNS-penetrant agent are evaluating whether to license one or exit the increasingly competitive RRMS market. Progressive MS — newly opened by tolebrutinib — is attracting deal interest.

MS-focused investors and biotech analysts

Investors covering neurology use trial registrations and status changes as leading indicators. A new Phase 3 start for a BTK inhibitor in progressive MS or a Phase 2 readout for a remyelination program can precede significant valuation events by 12–24 months. The biosimilar entries also signal margin compression for ocrelizumab-dependent revenue models.

Medical affairs at established MS companies

Medical affairs teams at Roche, Novartis, Sanofi, TG Therapeutics, and BMS track competitors' clinical programs to anticipate label changes, prepare for new competitive entries, and inform KOL engagement. The BTK approval of tolebrutinib has already changed the SPMS conversation at most major MS companies.

MS research networks and patient advocacy organizations

Organizations like the National MS Society and patient advocacy networks track new recruiting trials to connect patients — particularly those with progressive MS who have fewer options — with appropriate study opportunities.

Frequently asked questions

How many active multiple sclerosis clinical trials are there in 2026?

As of March 2026, there are 300 active multiple sclerosis clinical trials on ClinicalTrials.gov, with 185 recruiting or active. The Phase 3 pipeline includes 32 programs spanning relapsing MS, progressive MS, and pediatric MS.

Which BTK inhibitors are in Phase 3 for MS?

Four BTK inhibitors are in active or recruiting Phase 3 MS programs: tolebrutinib (Sanofi, FDA-approved for nrSPMS June 2025, also Phase 3 RRMS), fenebrutinib (Hoffmann-La Roche, FENopta 1 and 2 vs. teriflunomide), remibrutinib (Novartis, RRMS and SPMS), and orelabrutinib (Zenas BioPharma/BeiGene, SPMS). Merck's evobrutinib failed Phase 3 in 2023.

Is tolebrutinib approved for multiple sclerosis?

Yes. The FDA approved tolebrutinib (Sanofi) in June 2025 for non-relapsing secondary progressive MS — the first BTK inhibitor and the first new mechanism approved for progressive MS in years. Tolebrutinib is also in Phase 3 for relapsing MS and non-relapsing progressive MS via two separate recruiting trials.

Are there ocrelizumab biosimilars in development?

Yes. As of 2026, two ocrelizumab biosimilar programs are in Phase 3: Amgen ABP 692 (NCT06700343) and a Sandoz biosimilar (NCT06847724), both recruiting for comparative studies against reference Ocrevus in relapsing MS.

Can I track RRMS and progressive MS separately?

Yes. On the Pro plan ($99/month), you can create unlimited watchlists — for example, one for RRMS programs, one for progressive MS (PPMS + SPMS), and one for remyelination/neuroprotection research.

Does DataLookout cover pediatric MS trials?

Yes. Pediatric MS trials on ClinicalTrials.gov are included. Notable current example: Novartis's Phase 3 study evaluating ofatumumab and siponimod vs. fingolimod in pediatric MS (NCT04926818).

How current is the multiple sclerosis trial data?

DataLookout fetches from ClinicalTrials.gov every morning. Studies posted or updated in the preceding 24 hours appear in that day's digest. Trial counts on this page were last verified March 2026 against the live ClinicalTrials.gov API.