Fenebrutinib vs Teriflunomide for Multiple Sclerosis

(FENhance 2 Trial)

No longer recruiting at 208 trial locations

Overseen By Reference Study ID Number: GN42272 https://forpatients.roche.com/

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Systemic corticosteroids, Immunosuppressants

Disqualifiers: Cancer, Cardiovascular, Psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of fenebrutinib, a new potential drug, with teriflunomide in treating relapsing multiple sclerosis (RMS), focusing on slowing disability and reducing relapse rates. Participants will receive either fenebrutinib or teriflunomide through random assignment. If results demonstrate a favorable balance of benefits and risks, an open-label phase may allow all participants to receive fenebrutinib. The trial seeks individuals diagnosed with RMS who have experienced symptoms for less than 10 years and can perform basic physical tests, such as walking 25 feet in under 150 seconds. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that any previous treatment with immunomodulatory or immunosuppressive medication requires an appropriate washout period (time without taking certain medications). It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that fenebrutinib is generally well tolerated. Patients using fenebrutinib experienced low relapse rates and did not develop new brain lesions or worsening disability after nearly two years. Its safety in multiple sclerosis (MS) aligns with its use in other conditions like rheumatoid arthritis and lupus.

Research has indicated that teriflunomide is a relatively safe option for treating MS. In studies involving over 2,000 patients, teriflunomide was used without major safety concerns. It is approved for relapsing forms of MS, suggesting its safety is well established for this purpose.

Both treatments appear safe, with fenebrutinib showing promising results in reducing MS symptoms and teriflunomide having a strong safety record over long-term use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about fenebrutinib for multiple sclerosis because it represents a fresh approach to treatment. Unlike current standard therapies such as interferon beta and glatiramer acetate, which primarily modulate the immune response, fenebrutinib is a Bruton's tyrosine kinase (BTK) inhibitor. This means it targets specific pathways in immune cells, potentially offering more precise control over inflammatory processes that contribute to multiple sclerosis. Additionally, this novel mechanism might lead to fewer side effects, making it an appealing option for patients seeking alternatives to traditional therapies.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

Research has shown that fenebrutinib, which participants in this trial may receive, is a promising treatment for relapsing multiple sclerosis (RMS). Studies indicate it significantly reduces new brain lesions and maintains low disease activity for nearly two years. Patients taking fenebrutinib experienced fewer relapses, with no new brain lesions or worsening of disability. In contrast, teriflunomide, another treatment option in this trial, is a well-established treatment for RMS. It effectively reduces the number of relapses per year and slows the progression of disability. Both treatments manage RMS effectively, with fenebrutinib as a newer option and teriflunomide as a proven one. ^{1 2 4 5 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Adults with Relapsing Multiple Sclerosis (RMS) who can perform specific physical tests, have an EDSS score of 0-5.5, and meet the revised 2017 McDonald Criteria for RMS diagnosis. Participants must agree to contraception if of childbearing potential and not plan to donate eggs or sperm. Exclusions include those with certain infections, a history of cancer within 10 years, severe allergies or intolerances, immunodeficiencies like HIV, recent vaccinations or steroid treatments, liver issues such as cirrhosis or Gilbert's Syndrome.

Inclusion Criteria

I can walk 25 feet in less than 150 seconds.

I can complete a manual dexterity test in less than 4 minutes with each hand.

My disability level allows me to walk without aid or rest for 200 meters.

Exclusion Criteria

I have not received a live vaccine in the last 6 weeks.

My blood tests show I have low blood cell counts.

I have had cancer, including blood or solid tumors, in the last 10 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either fenebrutinib or teriflunomide in a double-blind fashion

96 weeks

Visits at Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, and 96

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if a positive benefit-risk result is observed

What Are the Treatments Tested in This Trial?

Interventions

• Fenebrutinib
• Placebo
• Teriflunomide

Trial Overview The trial is testing Fenebrutinib against Teriflunomide in adults with RMS to see which is better at slowing disability progression and reducing relapse rate. Participants are randomly assigned to one of the two drugs in equal numbers. The study may extend based on positive initial results.

How Is the Trial Designed?

Group I: Fenebrutinib Experimental Treatment 2 Interventions

Participants will receive oral fenebrutinib with teriflunomide-matching placebo.

Group II: Teriflunomide Active Control 2 Interventions

Participants will receive oral teriflunomide with fenebrutinib-matching placebo in a blinded fashion.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Teriflunomide (Aubagio®) is an effective oral treatment for relapsing multiple sclerosis (MS), showing significant improvements in clinical outcomes and MRI measures compared to placebo and similar efficacy to interferon β-1a, based on extensive randomized controlled trials and real-world evidence.

The drug is generally well tolerated, with long-term treatment (≥ 10 years) showing sustained benefits and no new safety concerns, making it a convenient option for managing relapsing-remitting MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide: A Review in Relapsing-Remitting Multiple Sclerosis. Scott, LJ.[2021]

Teriflunomide (Aubagio®) is an effective once-daily oral treatment for relapsing forms of multiple sclerosis (RMS), approved in multiple regions including Europe and North America.

The review discusses teriflunomide's safety and efficacy based on extensive clinical trials, while also exploring its therapeutic mechanism of action, which is still being researched through various studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. Bar-Or, A.[2021]

In a real-world study involving 200 patients with relapsing multiple sclerosis, teriflunomide demonstrated stable quality of life over 24 months, with significant reductions in relapse activity compared to the pre-baseline period.

The study indicated high treatment adherence and acceptability of teriflunomide, as reflected in patient-reported outcomes, with no substantial changes in fatigue and a marginal increase in reported disability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes. Hestvik, ALK., Frederiksen, JL., Nielsen, HH., et al.[2022]

In a study of 1128 patients with relapsing-remitting multiple sclerosis, teriflunomide significantly reduced the annualized relapse rate from 0.87 to 0.35 over 24 months, indicating its effectiveness in managing the disease.

Patient satisfaction with teriflunomide was high, with significant improvements in effectiveness, convenience, and overall satisfaction reported after 24 months, while the safety profile was consistent with previous clinical trials, with 35.8% experiencing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study. Kallmann, BA., Tiel-Wilck, K., Kullmann, JS., et al.[2022]

Teriflunomide (Aubagio®) is an oral medication that works by targeting the mitochondrial enzyme dihydroorotate dehydrogenase, helping to modulate the immune response in patients with relapsing-remitting multiple sclerosis (MS).

On June 18, 2021, teriflunomide was approved for use in pediatric patients aged 10 years and older in the EU, marking a significant milestone in its development for treating MS in younger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide: Pediatric First Approval. Paik, J.[2021]

Citations

1. gene.com gene.com/media/press-releases/15064/2025-05-29/genentechs-fenebrutinib-maintains-near-c

Phase III studies for fenebrutinib in relapsing and primary ... Patients on fenebrutinib had low relapse rates with data showing no active brain lesions or disability progression after nearly two years of ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40683275/

Safety and efficacy of fenebrutinib in relapsing multiple ... Interpretation: Fenebrutinib was well tolerated and exerted an early, robust, and sustained effect of limiting new focal brain lesions. Further studies are ...

3. roche.com roche.com/media/releases/med-cor-2025-05-30

Roche's fenebrutinib maintains near-complete suppression ... Patients on fenebrutinib had low relapse rates with data showing no active brain lesions or disability progression after nearly two years of ...

4. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(25)00174-7/abstract

Safety and efficacy of fenebrutinib in relapsing multiple ... Fenebrutinib was well tolerated and exerted an early, robust, and sustained effect of limiting new focal brain lesions. Further studies are needed to better ...

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000209016

Fenebrutinib Maintains Low Disease Activity in Relapsing ... Fenebrutinib reduced disease activity in relapsing multiple sclerosis (RMS) and demonstrated central nervous system penetrance.

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000205291

The Safety Profile of Fenebrutinib in Patients with Multiple ... Conclusions: The safety and tolerability profile of fenebrutinib in MS remains consistent with that in previously studied AIs (RA, SLE and CSU).