Genentech Expands Its Multiple Sclerosis Portfolio With Investigational BTK Inhibitor Fenebrutinib and Initiates Novel Clinical Trials for Ocrevus (ocrelizumab)

• Phase III clinical trial program initiated for investigational medicine fenebrutinib, designed to be a highly selective and reversible Bruton’s tyrosine kinase (BTK) inhibitor, in relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS)
• Phase IIIb clinical trial program of higher-dose Ocrevus to evaluate impact on reducing disability progression in RMS and PPMS
• Ocrevus CHIMES study exclusively focused on disease insights and more tailored care for minority populations with MS

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced the initiation of an innovative Phase III clinical trial program for its investigational medicine fenebrutinib in multiple sclerosis (MS), along with a higher-dose Phase III clinical trial program for Ocrevus^® (ocrelizumab) and a distinct Ocrevus trial specifically to support African-American and Hispanic- and Latinx-American patients with MS. Overviews of clinical trials and scientific rationale will be presented at MSVirtual2020, the 8th Joint Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) from September 11-13, 2020.

“We remain committed to advancing the science in MS by investigating potential new medicines such as fenebrutinib, with the ultimate goal of halting progression of this disease,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “In addition, over 170,000 people have been treated with Ocrevus, our first-in-class B-cell therapy, and we are incorporating years of clinical trial data and real-world evidence to optimize its potential to improve outcomes for patients with MS.”

Fenebrutinib Phase III clinical trial program

Genentech is initiating a Phase III clinical trial program for fenebrutinib, an investigational oral Bruton’s tyrosine kinase (BTK) inhibitor in relapsing MS (RMS) and primary progressive MS (PPMS). Increasing evidence suggests that B cells and myeloid lineage cells contribute to disease progression in MS. Fenebrutinib is a dual inhibitor of both B-cell and myeloid lineage-cell activation, which may conceivably offer a novel approach to suppress disease activity and slow disease progression by targeting both acute and chronic inflammatory aspects of MS, which will be studied in the Phase III clinical trial program. Pre-clinical data have shown fenebrutinib is highly selective and acts as a non-covalent agent with a slow release rate from its target.

The Phase III clinical trial program includes two identical Phase III trials in RMS (named FENhance 1 and FENhance 2) and one Phase III trial in PPMS (named FENtrepid). All three trials are targeting clinical disability progression and have a primary endpoint of 12-week composite confirmed disability progression (cCDP-12), with the addition of a co-primary endpoint of annualized relapse rate in the RMS trials. The PPMS study is the first study in this patient population to have an active comparator – Ocrevus – rather than placebo.

Ocrevus higher dose Phase IIIb clinical trial program

Halting disease progression is the ultimate aim for patients and physicians, and we are acting on the needs of the MS community, informed by recent data, to optimize the potential of Ocrevus to slow progression for a broad range of patients. Genentech is therefore initiating two new Phase IIIb trials, one in RMS (named MUSETTE) and one in PPMS (named GAVOTTE), which will evaluate a higher Ocrevus dose compared with the currently approved 600 mg dose, with both evaluated at the twice-yearly (six-monthly) dosing schedule. This decision was based on analyses from the pivotal RMS and PPMS studies presented at the American Academy of Neurology Annual Meeting 2019, which showed higher Ocrevus exposure was associated with lower B-cell levels and with greater control of disability progression, without impacting safety.

At the currently approved 600 mg dose, Ocrevus is the only MS treatment that has demonstrated a consistent and significant impact on slowing disability progression in both RMS and PPMS Phase III studies. The clinical trial program will evaluate the potential benefit of higher dose Ocrevus in further reducing disability progression for people living with both RMS and PPMS.

Ocrevus CHIMES trial in minority patients

Genentech recently initiated the Phase IV CHIMES (CHaracterization of ocrelizumab In Minorities with multiplE Sclerosis) trial in African-American and Hispanic- and Latinx-Americans with RMS. These patient populations are more likely to experience more relapses and greater disability than Caucasians, yet are vastly underrepresented in most clinical trials.

CHIMES is the first prospective trial developed in collaboration with MS patients, patient advocacy groups and investigators to exclusively focus on meeting the needs of minority patients with MS. The findings are expected to improve current understanding of MS disease biology and treatment response, among African-American and Hispanic- and Latinx-American patients with MS, with the ultimate goal of increasing high-quality standard of care to traditionally underserved communities and enhancing equality through clinical research. To learn more about Genentech’s efforts in this area, please visit http://www.gene.com/inclusiveresearch.

All of the newly announced clinical trials are underway and anticipated to begin recruiting in the coming months.

About multiple sclerosis

Multiple sclerosis (MS) is a chronic disease that affects nearly one million people in the United States, for which there is currently no cure. MS occurs when the immune system abnormally attacks the insulation and support around nerve cells (myelin sheath) in the brain, spinal cord and optic nerves, causing inflammation and consequent damage. This damage can cause a wide range of symptoms, including muscle weakness, fatigue and difficulty seeing, and may eventually lead to disability. Most people with MS experience their first symptom between 20 and 40 years of age, making the disease the leading cause of non-traumatic disability in younger adults.

Relapsing-remitting MS (RRMS) is the most common form of the disease and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. Approximately 85 percent of people with MS are initially diagnosed with RRMS. The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive MS (SPMS), in which they experience steadily worsening disability over time. Relapsing forms of MS (RMS) include people with RRMS and people with SPMS who continue to experience relapses. Primary progressive MS (PPMS) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately 15 percent of people with MS 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.

People with all forms of MS experience disease activity – inflammation in the nervous system and permanent loss of nerve cells in the brain – even when their clinical symptoms aren’t apparent or don’t appear to be getting worse. An important goal of treating MS is to reduce disease activity as soon as possible to slow how quickly a person’s disability progresses. Despite available disease-modifying treatments (DMTs), some people with RMS continue to experience disease activity and disability progression.

About fenebrutinib

Fenebrutinib is designed to be a highly selective small molecule and is the only reversible (non-covalent) BTK inhibitor currently in Phase III development in MS. Increasing evidence suggests that B cells and myeloid lineage cells contribute to disease progression in MS. Fenebrutinib is a dual inhibitor of both B-cell and myeloid lineage-cell activation, which may offer a novel approach to suppress disease activity and slow disease progression by targeting both acute and chronic inflammatory aspects of MS, which will be studied in our Phase III clinical trial program. The safety profile of fenebrutinib has been studied in more than 1,200 people to date across several inflammatory diseases, and the data indicate that the high selectivity of fenebrutinib may limit off-target effects.

About Ocrevus^® (ocrelizumab)

Ocrevus is the first and only therapy approved for both RMS (including clinically isolated syndrome, RRMS and active, or relapsing, SPMS) and PPMS, with dosing every six months. 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. This nerve cell damage can lead to disability in people with MS. Based on preclinical studies, Ocrevus binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, suggesting that important functions of the immune system may be preserved.

Ocrevus is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.

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 or 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: Ocrevus can cause infusion reactions that can be serious and 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:
  • Ocrevus increases your risk of getting upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes infections. 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 signs of herpes (such as cold sores, shingles, or genital sores). These signs can happen during treatment or after you have received your last dose of Ocrevus. If you have an active infection, your healthcare provider should delay your treatment with Ocrevus until your infection is gone.
  • Progressive Multifocal Leukoencephalopathy (PML): Although no cases have been seen with Ocrevus treatment in clinical trials, PML may happen with Ocrevus. PML is a rare brain infection that usually leads to death or severe disability. Tell your healthcare provider right away if you have any new or worsening neurologic signs or symptoms. These may include problems with thinking, balance, eyesight, weakness on 1 side of your body, strength, or using your arms or legs.
  • 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.

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 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 are pregnant or planning to become pregnant talk to your doctor about vaccinations for your baby, as some precautions may be needed.
• 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.
• 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.

Most common side effects include infusion reactions and infections.

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.

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

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

About Genentech in neuroscience

Neuroscience is a major focus of research and development at Genentech and Roche. 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, stroke, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Duchenne muscular dystrophy and autism spectrum disorder. 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 more than 40 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.

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