Sunday, Nov 9, 2025

Genentech’s Fenebrutinib Shows Unprecedented Positive Phase III Results as the Potential First and Only BTK Inhibitor in Both Relapsing and Primary Progressive Multiple Sclerosis

The first (FENhance 2) of two pivotal RMS studies met its primary endpoint, showing investigational fenebrutinib significantly reduced relapses compared to teriflunomide

 

In a pivotal PPMS study (FENtrepid), fenebrutinib slowed disability progression at least as effectively as Ocrevus, the only approved therapy in PPMS

 

Full data from both studies will be shared at upcoming medical meetings; once the second RMS study (FENhance 1) has read out, which is expected in the first half of 2026, all data together will be considered for submission to regulatory authorities

South San Francisco, CA -- November 9, 2025 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the first Phase III (FENhance 2) of two pivotal, similarly-designed Phase III studies (FENhance 1 and 2) in patients with relapsing multiple sclerosis (RMS) met its primary endpoint. Fenebrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, significantly reduced the annualized relapse rate (ARR) compared to teriflunomide over a period of at least 96 weeks of treatment. 

 

Additionally, the Phase III FENtrepid pivotal study evaluating fenebrutinib, compared with Ocrevus^® (ocrelizumab) in patients with primary progressive multiple sclerosis (PPMS), met its primary endpoint. The results showed that fenebrutinib was non-inferior compared to ocrelizumab, the only approved therapy in PPMS, as measured by a delay in the onset of composite confirmed disability progression over a period of at least 120 weeks of treatment. A numerical benefit for fenebrutinib compared to ocrelizumab was seen as early as week 24, and lasted throughout the observation period.

 

“Fenebrutinib substantially reduced the number of relapses in RMS and slowed disability progression in PPMS. These unprecedented results suggest that fenebrutinib could potentially become a best-in-disease medicine as the first high-efficacy, oral treatment for people with RMS or PPMS,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. "Therefore, these pivotal results for fenebrutinib may offer new hope for people living with MS, and they reaffirm our enduring commitment to the MS community.”

 

Liver safety was consistent with previous fenebrutinib studies. Additional safety data is being further evaluated. The results of the second RMS Phase III trial (FENhance 1) are expected by the first half of 2026.

 

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 BTKi, 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 similarly designed 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). Key secondary endpoints include the time to onset of composite 24-week confirmed disability progression (cCDP24), 12-week confirmed disability progression (CDP12) and 24-week confirmed disability progression (CDP24).

 

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 the FENtrepid study

FENtrepid is a Phase III multicenter, randomized, double-blind, double-dummy, parallel-group study to evaluate the efficacy and safety of fenebrutinib compared with Ocrevus in 985 adult patients with PPMS. Eligible participants were randomized 1:1 to receive treatment with either daily oral fenebrutinib (and placebo matched to intravenous [IV] Ocrevus) or IV Ocrevus (and placebo matched to oral fenebrutinib) for at least 120 weeks. 

 

The primary endpoint is the time to onset of 12-week composite confirmed disability progression (cCDP12). The cCDP incorporates three measures of disability – total functional disability measured by 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). This comprehensive composite endpoint offers greater sensitivity than the EDSS alone, capturing additional aspects of disability and often earlier. Key secondary endpoints include the time to onset of 24-week composite confirmed disability progression (cCDP24), 12-week confirmed disability progression (CDP12) and 24-week confirmed disability progression (CDP24). 

 

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 has been shown to be 130 times more selective for BTK vs. other kinases. Fenebrutinib is an inhibitor of both B-cell and microglia activation. This dual inhibition may be able to reduce both multiple sclerosis disease activity and disability progression, thereby potentially addressing the key unmet medical need of disability progression in people living with multiple sclerosis and providing comprehensive multiple sclerosis care. 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. 

 

About Ocrevus^® (ocrelizumab)

Ocrevus is a humanized monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. Ocrevus IV and Ocrevus subcutaneous (SC; marketed as Ocrevus Zunovo^® [ocrelizumab hyaluronidase-ocsq] in the U.S.) are the only therapies approved for both RMS (including relapsing-remitting multiple sclerosis [RRMS] and active, secondary progressive multiple sclerosis [SPMS], as well as clinically isolated syndrome [CIS] in the U.S.) and primary progressive multiple sclerosis (PPMS). Both Ocrevus IV and SC are administered every six months. The initial IV dose is given as two 300 mg infusions two weeks apart with subsequent doses given as single 600 mg infusions. Ocrevus SC is given as a single 920 mg subcutaneous injection every six months.

 

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 have a relapsing form of the disease (RMS) characterized by relapses and also 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.

 

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 nearly 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 are Ocrevus and Ocrevus Zunovo?

Ocrevus and Ocrevus Zunovo are prescription medicines 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 and Ocrevus Zunovo are safe and effective in children.

 

Who should not receive Ocrevus or Ocrevus Zunovo? 

Do not receive Ocrevus or Ocrevus Zunovo if you:

• have an active hepatitis B virus (HBV) infection.
• have had a life-threatening administration reaction to ocrelizumab.
• have had a life-threatening allergic reaction to ocrelizumab, hyaluronidase, or any of the ingredients of Ocrevus Zunovo. Tell your healthcare provider if you have had an allergic reaction to Ocrevus or Ocrevus Zunovo or any of their ingredients in the past.

 

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

Ocrevus and Ocrevus Zunovo can cause serious side effects, including:

• Infusion reactions (Ocrevus): 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. 
• Injection reactions (Ocrevus Zunovo): Injection reactions are a common side effect of Ocrevus Zunovo, which can be serious and may require you to be hospitalized. You will be monitored for signs and symptoms of an injection reaction when you receive Ocrevus Zunovo. This will happen during all injections for at least 1 hour after your first injection, and for at least 15 minutes after all injections following the first injection.   

 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

 

  Additionally, for Ocrevus Zunovo:

• Injection site pain
• Swelling
• Redness

 

These infusion and injection reactions can happen during or up to 24 hours after administration. 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 or injection.

 

• Infection: 
  • Infections are a common side effect. Ocrevus and Ocrevus Zunovo increase your risk of getting upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes infections. Serious infections can happen with Ocrevus and Ocrevus Zunovo, 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, or 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 or Ocrevus Zunovo. Tell your healthcare provider right away if you have an infection. Your healthcare provider should delay your treatment with Ocrevus or Ocrevus Zunovo until your infection is gone.
  • Hepatitis B virus (HBV) reactivation: Before starting treatment with ocrelizumab, 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 or Ocrevus Zunovo. 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 or Ocrevus Zunovo. 
  • Weakened immune system: Ocrevus or Ocrevus Zunovo 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 ocrelizumab. 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 and Ocrevus Zunovo 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 or Ocrevus Zunovo, tell your healthcare provider about all of your medical conditions, including if you:

• have or think you have an infection. See “What is the most important information I should know about Ocrevus and Ocrevus Zunovo?”
• have ever taken, take, or plan to take medicines that affect your immune system, or other treatments for MS. These medicines could increase your risk of getting an infection. 
• 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 or Ocrevus Zunovo. You should not receive ‘live’ or ‘live-attenuated’ vaccines while you are being treated with Ocrevus or Ocrevus Zunovo 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 or Ocrevus Zunovo. If you would like to receive any non-live (inactivated) vaccines, including the seasonal flu vaccine, while you are being treated with Ocrevus or Ocrevus Zunovo, talk to your healthcare provider. 
• If you have a baby and you received Ocrevus or Ocrevus Zunovo during your pregnancy, it is important to tell your baby’s healthcare provider about receiving Ocrevus or Ocrevus Zunovo 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 and Ocrevus Zunovo will harm your unborn baby. You should use birth control (contraception) during treatment with Ocrevus and Ocrevus Zunovo and for 6 months after your last dose of Ocrevus or Ocrevus Zunovo. 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 or Ocrevus Zunovo.
• are breastfeeding or plan to breastfeed. It is not known if Ocrevus and Ocrevus Zunovo pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Ocrevus or Ocrevus Zunovo. 

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 and Ocrevus Zunovo? 

Ocrevus and Ocrevus Zunovo 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 and Ocrevus Zunovo may cause liver damage. Your healthcare provider will do blood tests to check your liver before you start Ocrevus or Ocrevus Zunovo and while you take Ocrevus or Ocrevus Zunovo 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

 

The most common side effects of Ocrevus Zunovo include:

• Injection reactions
• Respiratory tract infections
• Skin infections

 

These are not all the possible side effects of Ocrevus and Ocrevus Zunovo. 

 

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 for Ocrevus.

 

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

 

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