Genentech's Fenebrutinib Confirms Its Potential as First and Only BTK Inhibitor for Relapsing and Primary Progressive MS in Third Positive Phase III Study (FENhance 1)

- FENhance 1 met its primary endpoint, showing investigational fenebrutinib significantly reduced relapses by 51% compared to teriflunomide in relapsing multiple sclerosis (RMS), consistent with FENhance 2 results showing 59% reduction -

- FENhance 1 is the final study readout of the fenebrutinib pivotal clinical development program in MS, following positive results for FENhance 2 in RMS and for FENtrepid in primary progressive multiple sclerosis (PPMS) -

- Fenebrutinib has the potential to become the first and only high-efficacy oral, brain-penetrant treatment for both RMS and PPMS, showing a profound benefit on relapsing and progressive disease biology -

- Totality of data from all three Phase III fenebrutinib studies will be submitted to regulatory authorities -

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the pivotal Phase III study (FENhance 1) of fenebrutinib in RMS met its primary endpoint, showing clinically meaningful and statistically significant results. The study demonstrated that fenebrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, markedly reduced the annualized relapse rate (ARR) by 51% compared to teriflunomide over a period of at least 96 weeks of treatment, consistent with FENhance 2 results showing a 59% reduction in ARR. Together, these results equate to approximately one relapse every 17 years. Secondary endpoints in both RMS studies show statistically significant and clinically meaningful reductions in brain lesions. Additionally, all progression endpoints show favorable trends for fenebrutinib.

Full data from the FENhance 1 and 2 studies will be shared at the American Academy of Neurology (AAN) Annual Meeting 2026 and submitted to regulatory authorities together with data from the FENtrepid study.

“These pivotal results, together with the earlier data, provide convincing evidence that fenebrutinib can become the first high-efficacy oral treatment for RMS and PPMS,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Building on a decade of transforming MS treatment, we are committed to advancing innovation to one day allow people with MS to live a life without disability.”

The positive FENhance 1 study follows positive results for FENhance 2 in RMS and for FENtrepid in PPMS, which were both announced in November. The collective positive results across all three pivotal studies demonstrate that fenebrutinib consistently shows a profound benefit on relapsing and progressive disease biology.

In both RMS studies, liver transaminase elevations were comparable with teriflunomide. In the FENhance 1 study, there was one Hy’s Law case in the fenebrutinib arm and one in the teriflunomide arm. Both cases were asymptomatic and resolved after study drug discontinuation. There were no additional Hy's Law cases across all of the fenebrutinib clinical development program in MS or in other autoimmune diseases.

In the FENhance 1 and 2 studies in RMS, 1 fatal case was reported in the teriflunomide arm and 8 fatal cases with various causes and at different points in treatment in the fenebrutinib arms. Further analyses are ongoing to better understand these findings.

Fenebrutinib targets cells in the immune system known as B cells and microglia. Targeting B cells helps control the acute inflammation that causes relapses, while targeting microglia inside the brain addresses the chronic damage that is thought to drive long-term disability progression. Fenebrutinib, a non-covalent BTK inhibitor, is designed to have high potency, selectivity and reversibility. This design allows it to act throughout the body, and also to cross the blood-brain barrier into the central nervous system (CNS) targeting chronic inflammation.

About the FENhance 1 and 2 studies

FENhance 1 and 2 are two Phase III multicenter, randomized, double-blind, double-dummy, parallel-group studies to evaluate the efficacy and safety of investigational fenebrutinib compared with teriflunomide in a total of 1,497 adult patients with RMS. Eligible participants were randomized 1:1 to receive treatment with either oral fenebrutinib twice a day (and placebo matched to oral teriflunomide once a day) or oral teriflunomide once a day (and placebo matched to oral fenebrutinib twice a day) for at least 96 weeks.

The primary endpoint is annualized relapse rate (ARR). Secondary endpoints include total number of T1-gadolinium-enhancing MRI lesions, total number of new and/or enlarging T2-weighted MRI lesions, time to onset of 12-week composite confirmed disability progression (cCDP12) and 24-week cCDP (cCDP24). cCDP incorporates three measures of disability – total functional disability measured by confirmed disability progression (CDP) based on the Expanded Disability Status Scale (EDSS), walking speed measured by the timed 25-foot walk (T25FW) and upper limb function measured by the nine-hole peg test (9HPT).

Following the double-blind treatment period, patients have the option to enter an open-label extension (OLE) phase, in which all patients receive treatment with fenebrutinib.

About fenebrutinib

Fenebrutinib is an investigational oral, central nervous system (CNS)-penetrant, reversible and non-covalent Bruton’s tyrosine kinase (BTK) inhibitor with an optimized pharmacokinetics (PK) profile. Fenebrutinib can act throughout the body and also cross the blood-brain barrier into the CNS to target chronic inflammation. It is uniquely designed to target relapsing and progressive biology by inhibiting cells in the immune system known as B cells and microglia. Targeting B cells helps control the acute inflammation that causes relapses, while targeting microglia inside the brain addresses the chronic damage that is thought to drive long-term disability progression.

Fenebrutinib is designed to have high potency and reversibility, with a selectivity for BTK 130 times greater than other kinases. This high selectivity highlights fenebrutinib's potential to bind to its intended target without interfering with other kinases. While most current BTK inhibitors are covalent and irreversible, meaning they form a permanent chemical bond with the enzyme, fenebrutinib is non-covalent and reversible, meaning it binds and then eventually releases the enzyme. These design features may help limit off-target effects.

The fenebrutinib Phase III program includes two similarly designed trials in relapsing multiple sclerosis (RMS) (FENhance 1 and 2) with active comparator teriflunomide and the only trial in primary progressive multiple sclerosis (PPMS) (FENtrepid) in which a BTK inhibitor is being evaluated against Ocrevus.

To date, more than 2,700 patients and healthy volunteers have been treated with fenebrutinib in Phase I, II and III clinical programs across multiple diseases, including multiple sclerosis and other autoimmune disorders.

About multiple sclerosis

Multiple sclerosis is a chronic disease that affects more than 2.9 million people worldwide. People with all forms of multiple sclerosis experience disease progression from the beginning of their disease. Therefore, an important goal of treating multiple sclerosis is to slow, stop and ideally prevent progression as early as possible.

Approximately 85% of people with multiple sclerosis are initially diagnosed with relapsing-remitting multiple sclerosis (RRMS). Relapsing forms of the disease (RMS) include RRMS and active secondary progressive MS, and people with RMS experience relapses and worsening disability over time. Primary progressive multiple sclerosis (PPMS) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately 15% of people with multiple sclerosis are diagnosed with the primary progressive form of the disease. Until the FDA approval of Ocrevus^®, there had been no FDA-approved treatments for PPMS and Ocrevus is still the only approved treatment for PPMS. Despite the availability of CD20s, 30% of patients remain on low-efficacy oral therapy today. Slowing or stopping progression while simultaneously stopping relapses remains a high unmet need in MS.

About Genentech in neuroscience

Neuroscience is a major focus of research and development at Genentech. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases.

Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Duchenne muscular dystrophy. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today.

About Genentech

Founded 50 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

Indications and Important Safety Information

What is Ocrevus?

Ocrevus is a prescription medicine used to treat:

• Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
• Primary progressive MS, in adults.

It is not known if Ocrevus is safe and effective in children.

Who should not receive Ocrevus?

Do not receive Ocrevus if you have an active hepatitis B virus (HBV) infection.

Do not receive Ocrevus if you have had a life-threatening allergic reaction to Ocrevus. Tell your healthcare provider if you have had an allergic reaction to Ocrevus or any of its ingredients in the past.

What is the most important information I should know about Ocrevus?

Ocrevus can cause serious side effects, including:

• Infusion reactions: Infusion reactions are a common side effect of Ocrevus, which can be serious and may require you to be hospitalized. You will be monitored during your infusion and for at least 1 hour after each infusion of Ocrevus for signs and symptoms of an infusion reaction. Tell your healthcare provider or nurse if you get any of these symptoms:
  • Itchy skin
  • Rash
  • Hives
  • Tiredness
  • Coughing or wheezing
  • Trouble breathing
  • Throat irritation or pain
  • Feeling faint
  • Fever
  • Redness on your face (flushing)
  • Nausea
  • Headache
  • Swelling of the throat
  • Dizziness
  • Shortness of breath
  • Fatigue
  • Fast heartbeat

These infusion reactions can happen for up to 24 hours after your infusion. It is important that you call your healthcare provider right away if you get any of the signs or symptoms listed above after each infusion.

If you get infusion reactions, your healthcare provider may need to stop or slow down the rate of your infusion.

• Infection:
  • Infections are a common side effect. Ocrevus increases your risk of getting upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes infections. Serious infections can happen with Ocrevus, which can be life-threatening or cause death. Tell your healthcare provider if you have an infection or have any of the following signs of infection including fever, chills, a cough that does not go away, or painful urination. Signs of herpes infection include: cold sores, shingles, genital sores, skin rash, pain, and itching. Signs of more serious herpes infection include: changes in vision, eye redness or eye pain, severe or persistent headache, stiff neck, and confusion. Signs of infection can happen during treatment or after you have received your last dose of Ocrevus. Tell your healthcare provider right away if you have an infection. Your healthcare provider should delay your treatment with Ocrevus until your infection is gone.
  • Hepatitis B virus (HBV) reactivation: Before starting treatment with Ocrevus, your healthcare provider will do blood tests to check for hepatitis B viral infection. If you have ever had hepatitis B virus infection, the hepatitis B virus may become active again during or after treatment with Ocrevus. Hepatitis B virus becoming active again (called reactivation) may cause serious liver problems including liver failure or death. Your healthcare provider will monitor you if you are at risk for hepatitis B virus reactivation during treatment and after you stop receiving Ocrevus.
  • Weakened immune system: Ocrevus taken before or after other medicines that weaken the immune system could increase your risk of getting infections.
• Progressive Multifocal Leukoencephalopathy (PML): PML is a rare brain infection that usually leads to death or severe disability and has been reported with Ocrevus. Symptoms of PML get worse over days to weeks. It is important that you call your healthcare provider right away if you have any new or worsening neurologic signs or symptoms that have lasted several days, including problems with:
  • Thinking
  • Eyesight
  • Strength
  • Balance
  • Weakness on 1 side of your body
  • Using your arms or legs
• Decreased immunoglobulins: Ocrevus may cause a decrease in some types of antibodies. Your healthcare provider will do blood tests to check your blood immunoglobulin levels.

Before receiving Ocrevus, tell your healthcare provider about all of your medical conditions, including if you:

• have ever taken, take, or plan to take medicines that affect your immune system, or other treatments for MS.
• have ever had hepatitis B or are a carrier of the hepatitis B virus.
• have a history of inflammatory bowel disease or colitis.
• have a history of liver problems
• have had a recent vaccination or are scheduled to receive any vaccinations.
  • You should receive any required ‘live’ or ‘live-attenuated’ vaccines at least 4 weeks before you start treatment with Ocrevus. You should not receive ‘live’ or ‘live-attenuated’ vaccines while you are being treated with Ocrevus and until your healthcare provider tells you that your immune system is no longer weakened.
  • When possible, you should receive any ‘non-live’ vaccines at least 2 weeks before you start treatment with Ocrevus. If you would like to receive any non-live (inactivated) vaccines, including the seasonal flu vaccine, while you are being treated with Ocrevus, talk to your healthcare provider.
  • If you have a baby and you received Ocrevus during your pregnancy, it is important to tell your baby’s healthcare provider about receiving Ocrevus so they can decide when your baby should be vaccinated.
• are pregnant, think that you might be pregnant, or plan to become pregnant. It is not known if Ocrevus will harm your unborn baby. You should use birth control (contraception) during treatment with Ocrevus and for 6 months after your last infusion of Ocrevus. Talk with your healthcare provider about what birth control method is right for you during this time. Tell your healthcare provider if you become pregnant while receiving Ocrevus.
• are breastfeeding or plan to breastfeed. It is not known if Ocrevus passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Ocrevus.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of Ocrevus?

Ocrevus may cause serious side effects, including:

• Risk of cancers (malignancies) including breast cancer. Follow your healthcare provider’s instructions about standard screening guidelines for breast cancer.
• Inflammation of the colon, or colitis: Tell your healthcare provider if you have any symptoms of colitis, such as:
  • Diarrhea (loose stools) or more frequent bowel movements than usual
  • Stools that are black, tarry, sticky or have blood or mucus
  • Severe stomach-area (abdomen) pain or tenderness
• Liver damage. Ocrevus may cause liver damage. Your healthcare provider will do blood tests to check your liver before you start Ocrevus and while you take Ocrevus if needed. Tell your healthcare provider right away if you have any symptoms of liver damage, such as:
  • yellowing of the skin and eyes (jaundice)
  • nausea
  • vomiting
  • unusual darkening of the urine
  • feeling tired or weak

These are not all the possible side effects of Ocrevus.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects to Genentech at (888) 835-2555.

For more information, go to https://www.Ocrevus.com or call 1-844-627-3887.

For additional safety information, please see the full Prescribing Information and Medication Guide.

Media Contact:
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Investor Contacts:
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