Drug stopping sits at the center of this dementia and brain health question.
A new class of oral medications called BTK inhibitors is poised to change the trajectory of multiple sclerosis by intercepting the disease’s destructive processes inside the brain itself — not just tamping down the immune system from the outside. Fenebrutinib, developed by Roche and Genentech, became the first investigational drug in over a decade to reduce disability progression in primary progressive MS, showing a 12% reduction in disability progression risk compared to Ocrevus, the only drug currently approved for that form of the disease. Its Phase III trials, FENtrepid and FENhance 2, met their primary endpoints in November 2025, and the company plans to file for regulatory approval after additional trial data expected in mid-first-half 2026.
But BTK inhibitors are only one front in a rapidly expanding war on MS. Researchers are also developing drugs that do something once considered impossible: rebuild the myelin sheath that MS destroys, effectively reversing nerve damage rather than merely slowing it. And a growing body of evidence linking Epstein-Barr virus to MS is opening the door to preventing the disease before it ever starts. This article covers the most significant drug developments, the promise and pitfalls of remyelination therapies, the high-efficacy treatments already on the market, and what the connection between a common virus and MS could mean for future generations.
Table of Contents
- Which Drugs Are Stopping Multiple Sclerosis Attacks Before They Happen?
- Remyelination Drugs That Could Reverse MS Damage
- High-Efficacy Approved Drugs Already Preventing Relapses
- Comparing Treatment Approaches — What Works for Which Stage of MS
- The Epstein-Barr Virus Connection and What It Means for Prevention
- Emerging Repair Compounds That Could Change the Game
- What the Next Two Years Could Look Like for MS Treatment
- Conclusion
- Frequently Asked Questions
Which Drugs Are Stopping Multiple Sclerosis Attacks Before They Happen?
The drugs generating the most excitement right now are BTK inhibitors, a class of small molecules that can cross the blood-brain barrier and suppress the inflammatory processes driving MS from within the central nervous system. Traditional MS therapies largely work by depleting or blocking immune cells in the bloodstream, which helps prevent relapses but does little to address the smoldering neuroinflammation behind the slow, relentless progression many patients experience. BTK inhibitors target Bruton’s tyrosine kinase, an enzyme involved in the activation of B cells and microglia — two cell types implicated in both relapsing and progressive forms of the disease. Fenebrutinib stands at the front of this class. Its significance lies not just in the trial results but in which patients it helped. Primary progressive MS has had essentially one approved treatment option — Ocrevus — since 2017. A 12% improvement over that drug’s already meaningful benefit is clinically relevant for a population that has been largely underserved.
By comparison, Sanofi’s tolebrutinib took a different path. The HERCULES trial demonstrated a 31% delay in six-month confirmed disability progression versus placebo in non-relapsing secondary progressive MS, a population with no approved therapies at all. On paper, those numbers looked transformative. However, the FDA issued a Complete Response Letter in December 2025, rejecting tolebrutinib’s approval. The agency flagged a serious liver injury risk — six cases meeting Hy’s Law criteria out of roughly 2,700 patients, including one death that required a liver transplant. The FDA called the drug-induced liver injury risk “among the highest in the class.” Regulators also questioned whether the efficacy signal was genuinely coming from patients with non-relapsing progressive MS or was instead driven by a subgroup with active disease, for whom approved therapies already exist. Sanofi continues discussions with the FDA to identify a viable patient population, but the rejection is a sobering reminder that promising trial data does not guarantee a clear path to patients.
Remyelination Drugs That Could Reverse MS Damage
For decades, the best MS treatments could only slow the disease. They could reduce relapses, delay disability accumulation, and quiet inflammation. What they could not do was repair the damage already done — the stripped myelin sheaths that leave nerve fibers exposed and dysfunctional. That is now changing. A drug called PIPE-307, developed by Contineum Therapeutics in collaboration with researchers at UCSF, represents a fundamentally different approach. Rather than suppressing the immune attack, it prompts the brain’s own precursor cells to mature into oligodendrocytes — the cells responsible for producing myelin — and rebuild the protective coating around nerves. PIPE-307 is a first-in-class drug that blocks the M1 muscarinic receptor. In preclinical models, it reversed nervous system degradation and recovered function, results that caught the attention of the broader neurology community.
The drug cleared Phase I safety trials in 2021 and is currently being evaluated in the VISTA Phase II trial, which enrolled 168 participants for approximately 30 weeks of dosing. The research builds on a decade of work by UCSF scientists Jonah Chan and Ari Green, who discovered that clemastine — a common over-the-counter antihistamine — could induce remyelination in MS patients. PIPE-307 was designed to be a more targeted, potent version of that finding. The limitation worth understanding is that remyelination therapies face a steep biological challenge. In advanced MS, the nerve fibers themselves — not just their myelin coating — can be irreversibly damaged. If the underlying axon has degenerated, rebuilding myelin around it accomplishes nothing. This means remyelination drugs are likely to be most effective earlier in the disease course, before extensive axonal loss has occurred. Separately, in October 2025, researchers identified two new compounds, K102 and K110, capable of regenerating myelin while also balancing immune responses. These are still in early stages, but they represent a growing pipeline of repair-oriented therapies that, if successful, could shift MS treatment from damage control to genuine restoration.
High-Efficacy Approved Drugs Already Preventing Relapses
While experimental therapies dominate headlines, several approved drugs are already doing a remarkable job of stopping MS attacks. Ublituximab, marketed as Briumvi, demonstrated striking efficacy in the ULTIMATE I trial published in the New England Journal of Medicine. The annualized relapse rate was 0.08 with ublituximab compared to 0.19 with teriflunomide — less than half. Even more dramatic was the reduction in gadolinium-enhancing lesions, a marker of active inflammation in the brain: 0.02 with ublituximab versus 0.49 with teriflunomide over 96 weeks. In practical terms, patients on ublituximab had almost no detectable new inflammatory activity. Ofatumumab, sold as Kesimpta, offers a different delivery model with similar mechanistic power.
Approved by the FDA in 2020 for relapsing MS, it is a self-injectable anti-CD20 monoclonal antibody that depletes the B cells responsible for orchestrating immune attacks on myelin. What distinguishes Kesimpta from older anti-CD20 drugs like Ocrevus is convenience — patients administer it at home with a prefilled pen, rather than sitting for hours-long intravenous infusions at a clinic. The important caveat is that all anti-CD20 therapies carry a meaningful infection risk. By depleting B cells, these drugs weaken the body’s ability to fight off certain infections and reduce the effectiveness of vaccines. For older adults or those with other health conditions, this tradeoff demands careful evaluation. The drugs are also primarily effective against the relapsing-inflammatory component of MS. Patients whose disease has transitioned to a predominantly progressive phase without relapses may see less benefit, which is precisely the gap that BTK inhibitors and remyelination drugs are trying to fill.
Comparing Treatment Approaches — What Works for Which Stage of MS
Choosing the right MS therapy is not simply a matter of picking the most powerful drug. It depends heavily on which form of MS a person has and how far the disease has progressed. For relapsing-remitting MS, the evidence strongly supports early treatment with high-efficacy drugs like ublituximab or ofatumumab. These medications can reduce relapse rates by 50% or more compared to older platform therapies and dramatically cut the number of new brain lesions. Starting aggressive treatment early — rather than escalating from weaker drugs — has been associated with better long-term outcomes in several observational studies. For primary progressive MS, the options have been painfully limited. Ocrevus remains the only approved therapy, and its benefits, while statistically significant, are modest in absolute terms.
Fenebrutinib’s 12% improvement over Ocrevus could be meaningful, but it also underscores how difficult this form of the disease is to treat. For secondary progressive MS without active relapses, nothing is currently approved, which made the tolebrutinib data so compelling — and its FDA rejection so deflating. The tradeoff patients and neurologists face is between efficacy and safety. The most potent drugs tend to carry the highest risks: infusion reactions, infections, and in the case of tolebrutinib, liver toxicity serious enough to halt its approval. Lower-risk drugs like dimethyl fumarate or teriflunomide are better tolerated but substantially less effective. For someone with aggressive, active disease, accepting higher risk often makes sense. For someone with stable, slowly progressing disease, the calculus may be different. There is no universal answer, which is why MS treatment remains deeply individualized.
The Epstein-Barr Virus Connection and What It Means for Prevention
Perhaps the most paradigm-shifting development in MS research has nothing to do with treatment at all. A growing body of epidemiological evidence has established that Epstein-Barr virus, the pathogen behind mononucleosis, is not merely associated with MS — it appears to be a necessary precondition for the disease. The data is striking: people who have never been infected with EBV have a near-zero risk of developing multiple sclerosis. In a landmark study tracking millions of military personnel, EBV infection preceded MS onset in virtually every case, and the risk of MS increased 32-fold after infection. This finding has enormous implications. If EBV is indeed the trigger, then an effective EBV vaccine could theoretically prevent most cases of MS from ever developing.
Several vaccine candidates are now in development, including an mRNA-based vaccine from Moderna that entered clinical trials. However, turning this scientific insight into a practical prevention strategy will take years, possibly decades. EBV infects more than 90% of the world’s population, usually during childhood or adolescence, and developing a vaccine that provides durable protection against a virus this common is a substantial technical challenge. The warning here is against premature optimism. Even if EBV is the initial trigger, MS clearly involves a complex cascade of genetic susceptibility, immune dysregulation, and environmental factors. Preventing EBV infection might eliminate the necessary spark, but it would not help the nearly one million Americans already living with MS. For them, the BTK inhibitors, remyelination therapies, and high-efficacy anti-CD20 drugs described above remain the most relevant advances.
Emerging Repair Compounds That Could Change the Game
Beyond PIPE-307, the pipeline of nerve repair therapies is expanding. In October 2025, researchers published findings on two new compounds, designated K102 and K110, that demonstrated the ability to regenerate the myelin sheath while simultaneously balancing immune responses — addressing both the cause and consequence of MS-related nerve damage. This dual mechanism is significant because previous remyelination attempts often ran into the problem of newly formed myelin being destroyed by the same ongoing immune attack that stripped it away in the first place.
These compounds are still in preclinical development, but they represent a broader trend in MS research: the recognition that stopping attacks alone is not enough. To truly change outcomes, treatments will need to repair what has already been lost. Combined with BTK inhibitors that can quiet the smoldering inflammation inside the brain, a future treatment regimen might involve one drug to halt the disease and another to undo its damage — a combination approach that was unthinkable a decade ago.
What the Next Two Years Could Look Like for MS Treatment
The MS treatment landscape is on the cusp of its most significant shift since the introduction of anti-CD20 therapies. If fenebrutinib receives regulatory approval — a decision likely to come in late 2026 or 2027 following the expected mid-2026 filing — it would become the first new mechanism of action approved for primary progressive MS in a decade. The PIPE-307 Phase II data, expected to read out from the VISTA trial, will reveal whether remyelination is achievable at clinically meaningful levels in humans, not just in laboratory mice.
Meanwhile, the Sanofi-FDA discussions around tolebrutinib will determine whether a BTK inhibitor can reach the non-relapsing progressive MS population under tighter safety monitoring protocols, or whether liver toxicity concerns will permanently sideline the drug for that indication. And the EBV vaccine research, while further from the finish line, could reshape how we think about MS from a disease to be managed into one to be prevented. For the millions of people living with MS today and the families watching for early signs, these are not abstract research milestones. They are potential turning points.
Conclusion
Multiple sclerosis treatment is moving beyond the suppress-and-hope model that has defined the field for three decades. BTK inhibitors like fenebrutinib offer the first brain-penetrant therapies capable of addressing progressive disease from inside the central nervous system, while high-efficacy approved drugs like ublituximab and ofatumumab continue to set new benchmarks for relapse prevention. The emergence of remyelination drugs — PIPE-307, K102, K110 — introduces the possibility of reversing damage rather than merely slowing its accumulation.
No single drug will stop MS in all its forms. The disease is too heterogeneous, too variable from person to person, and too dependent on timing and biology for a one-size-fits-all solution. But the convergence of BTK inhibitors, remyelination therapies, and EBV-linked prevention research means that the tools available to patients and neurologists are expanding faster than at any point in the history of the disease. For anyone affected by MS, staying informed about these developments — and having honest conversations with a neurologist about which advances are relevant to their specific situation — has never been more important.
Frequently Asked Questions
What is a BTK inhibitor and how is it different from current MS drugs?
BTK inhibitors are oral medications that block Bruton’s tyrosine kinase, an enzyme involved in activating B cells and microglia inside the central nervous system. Unlike most current MS drugs, which work primarily in the bloodstream, BTK inhibitors can cross the blood-brain barrier and target the smoldering neuroinflammation that drives progressive disability.
Is fenebrutinib approved yet?
Not yet. Fenebrutinib’s Phase III trials met their primary endpoints in November 2025, and Roche plans to submit for regulatory approval after additional trial data expected in mid-first-half 2026. An approval decision would likely follow in late 2026 or 2027.
Why was tolebrutinib rejected by the FDA?
The FDA issued a Complete Response Letter in December 2025 citing two concerns: a drug-induced liver injury risk described as “among the highest in the class” — including six cases meeting Hy’s Law and one death requiring a liver transplant — and questions about whether the efficacy was truly in non-relapsing progressive MS patients or driven by those with active disease who already have treatment options.
Can any drug currently reverse MS damage?
No approved drug can reverse MS damage yet. However, PIPE-307 is in Phase II trials and has shown the ability to prompt myelin regeneration in preclinical models. Two additional compounds, K102 and K110, have also demonstrated myelin repair capabilities in early research. These are not yet available to patients.
Does Epstein-Barr virus cause MS?
Epidemiological evidence strongly suggests EBV is a necessary precondition for MS — people never infected with EBV have near-zero MS risk. However, EBV alone is not sufficient to cause MS; genetic susceptibility and other environmental factors also play a role. Vaccine development targeting EBV is underway but years from clinical use.
What is the most effective approved drug for relapsing MS right now?
Several anti-CD20 monoclonal antibodies — including ublituximab (Briumvi) and ofatumumab (Kesimpta) — are among the most effective. In the ULTIMATE I trial, ublituximab reduced annualized relapse rates to 0.08 compared to 0.19 with teriflunomide, with near-complete suppression of new inflammatory brain lesions.
You Might Also Like
- New Vitiligo Drug Gets FDA Approval — First Topical Treatment Ever
- New Drug Approved for Alcohol Use Disorder — First in 20 Years
- New Drug for Postpartum Depression Works Faster Than Anything Before
For more, see CDC — Alzheimer’s and Dementia.
