• Late-breaking Phase III FENhance 1 and 2 study results showed superiority of investigational fenebrutinib compared to teriflunomide in reducing relapses and brain lesions in relapsing multiple sclerosis (RMS)
• Both studies showed positive trends in reducing disability progression with fenebrutinib compared to teriflunomide
• Fenebrutinib could become a first-in-class BTK inhibitor and the first and only high-efficacy oral for both RMS and primary progressive multiple sclerosis (PPMS)
• The totality of RMS and PPMS data for fenebrutinib will be submitted to regulatory authorities

Company Website: https://www.gene.com
SOUTH SAN FRANCISCO, Calif. -- (Business Wire)

Genentech, a member of the Roche Group (SIX: RO, ROP; OTCQX: RHHBY), announced today new data from the positive Phase III FENhance 1 and 2 studies, which met their primary endpoint. The studies showed that fenebrutinib, an investigational non-covalent Bruton’s tyrosine kinase (BTK) inhibitor, reduced the annualized relapse rate (ARR) by 51.1% (p<0.001) in FENhance 1 and 58.5% (p<0.0001) in FENhance 2 compared with teriflunomide in patients with relapsing multiple sclerosis (RMS) over 96 weeks. This equates to patients having approximately one relapse every 17 years, more than half the relapses seen with teriflunomide in the same period of time. The results were shared today as a late-breaking presentation at the 2026 American Academy of Neurology (AAN) Annual Meeting in Chicago.

“These results underscore that fenebrutinib has potential as a high-efficacy oral treatment for RMS. Its unique mode of action may offer a differentiated profile by targeting dual drivers of MS within the central nervous system and periphery to address disease mechanisms underlying both relapsing and progressive disease biology,” said Jiwon Oh, M.D., Ph.D., Medical Director of the Barlo Multiple Sclerosis Program at St. Michael’s Hospital, University of Toronto. “For the first time, a BTK inhibitor has demonstrated superiority in reducing relapses and formation of new brain lesions with comparable rates of liver enzyme elevations to a long-standing first-line medication in multiple Phase III RMS trials.”

“The fenebrutinib data across three pivotal studies strongly support its potential to benefit people with both RMS and PPMS,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “By more than doubling the time without relapses compared to teriflunomide, fenebrutinib may offer patients years of relapse-free living, thereby preserving both daily independence and long-term function.”

The relapse rate was consistently reduced across patient subgroups. The greatest reductions were observed in patients with more inflammatory disease characteristics including active brain lesions, younger age, more recent diagnosis and less disability, which highlights the potential of fenebrutinib as a high-efficacy, oral treatment option for these patient populations, if approved.

Secondary endpoints showed that fenebrutinib significantly reduced disease activity in the brain, as evidenced by MRI scans. Fenebrutinib reduced markers of active inflammation by 70.7% (p<0.0001) in FENhance 1 and 77.6% (p<0.0001) in FENhance 2 compared with teriflunomide, as measured by new T1 gadolinium-enhancing (T1-Gd+) lesions. Chronic disease burden was reduced by 76.0% (p<0.0001) in FENhance 1 and 82.5% (p<0.0001) in FENhance 2 with fenebrutinib compared with teriflunomide, as measured by new or enlarging T2 lesions.

Additional secondary endpoints showed positive trends toward reducing disability progression with fenebrutinib. A numerical reduction in the risk of 12-week composite confirmed disability progression (cCDP12) by 20% (hazard ratio [HR] 0.80; 95% confidence interval [CI]: 0.63-1.02) in FENhance 1 and 13% (HR 0.87; 95% CI: 0.69-1.11) in FENhance 2 was observed with fenebrutinib compared with teriflunomide. 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). The greatest reductions were observed on overall disability and upper-limb disability. In a post-hoc analysis of a modified 12-week confirmed composite of the EDSS and the 9HPT, fenebrutinib reduced the risk of worsening by 26% (HR 0.74; 95% CI: 0.53-1.03) in FENhance 1 and 20% (HR 0.80; 95% CI: 0.57-1.12) in FENhance 2 compared with teriflunomide.

In both RMS studies, liver enzyme elevations above three times the upper limit of normal were comparable with teriflunomide (7.3% vs 5.7% in FENhance 1; 5.6% vs 5.6% in FENhance 2). In the FENhance 1 study, there was one Hy’s Law case in the fenebrutinib arm (which occurred before biweekly liver monitoring was implemented) and one in the teriflunomide arm. Both cases were asymptomatic and resolved after study drug discontinuation.

Rates of infections were also comparable between the fenebrutinib and teriflunomide arms. Serious adverse events (AEs) were reported in 8.6% of patients receiving fenebrutinib (vs 8.9% on teriflunomide) in FENhance 1 and 11.2% (vs 6.1%) in FENhance 2.

Overall, an imbalance with respect to reported fatalities across studies was observed. In FENhance 1 and 2, there was one death (0.1%) in the teriflunomide arm and seven deaths (0.9%) in the fenebrutinib arm during the reporting period. One additional death was observed after this period. Overall in the fenebrutinib arm, deaths occurred at different timepoints and were caused by various causes including infections (neuro cryptococcosis gattii and pneumonia), complications of type 1 diabetes, serious bleeding, suicide, injuries from accident and death of unknown cause.

Previously, the Phase III FENtrepid study in primary progressive multiple sclerosis (PPMS) showed fenebrutinib met its primary endpoint of non-inferiority compared with the current standard of care, Ocrevus^®, in reducing disability progression in PPMS. The collective positive results across all three pivotal studies demonstrate that fenebrutinib consistently showed a profound benefit on relapsing and progressive disease biology. The totality of data from all three Phase III fenebrutinib studies will be submitted to regulatory authorities.

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).

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.

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 neurology

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

Genentech and Roche are investigating more than a dozen medicines for neurological conditions, 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 neurology 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.

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Contacts:

Media Contact:
Michelle McCourt, (650) 467-6800

Advocacy Contact:
Lily Rose Atherton, (650) 690-5573

Investor Contacts:
Loren Kalm, (650) 225-3217
Bruno Eschli, +41 61 687 5284

Source: Genentech