Early Treatment With Genentech’s Ocrevus (ocrelizumab) Leads to Reduced Disease Progression and Healthcare Costs; Nine-Year Safety Data Reinforce Favorable Benefit-Risk Profile

– 77% of early-stage relapsing-remitting multiple sclerosis (RRMS) patients who had not received prior treatment achieved no evidence of disease activity (NEDA) at two years –

– Initiation of Ocrevus as first-line treatment reduces relapses, hospitalizations and costs compared with using Ocrevus in second-line setting –

– Nine-year long-term safety data for Ocrevus further reinforce favorable benefit-risk profile; more than 250,000 people have been treated globally –

– Pregnancy outcomes reported for more than 2,000 women with multiple sclerosis (MS) treated with Ocrevus do not suggest an increased risk of adverse pregnancy and infant outcomes –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new Ocrevus^® (ocrelizumab) data on disease progression and healthcare costs in patients with early-stage relapsing-remitting multiple sclerosis (RRMS) and long-term safety from all clinical trials in patients with relapsing MS (RMS) and primary progressive MS (PPMS). Data from the largest database of pregnancy outcomes for an anti-CD20 therapy in MS suggest consistent outcomes with epidemiological data in pregnant women and was an oral presentation today at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“MS often impacts young people at a time in their lives when they are starting a career or planning a family,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “These new data show that using Ocrevus as a first-line treatment brings substantial clinical and cost benefits to patients, thereby further emphasizing the efficacy that Ocrevus may bring with continued long-term use.”

Two-year interim analysis of open-label Phase IIIb ENSEMBLE: No evidence of disease progression in early-stage RRMS

Ocrevus treatment provided consistent benefit over two years in patients who were recently diagnosed with RRMS and had not received prior disease modifying treatment (DMT) in an interim analysis of open-label Phase IIIb study ENSEMBLE. After 96 weeks of Ocrevus treatment, 77% of patients achieved no evidence of disease activity (NEDA; no relapses, no worsening of disability or no evidence of MRI lesion activity with pre-specified MRI re-baselining at 8 weeks). The majority of patients had no relapses (93%), no MRI lesion activity (89%) and no 24-week confirmed disability progression (91%).

Over two years, the average annualized relapse rate (ARR) across all patients in the ENSEMBLE study was low (0.033), which equates to 1 relapse every 30 years. The mean Expanded Disability Status Scale (EDSS) score from baseline significantly improved from 1.8 to 1.67 (p<0.0001). The safety profile of Ocrevus in this trial was consistent with its overall favorable safety profile.

U.S. claims analysis: Early initiation of Ocrevus may benefit both patients and the healthcare system

Patients who were newly diagnosed and initiated Ocrevus treatment had a lower rate of annualized events often associated with a relapse (EOAR; 0.36) compared with patients who initiated Ocrevus as a second-line or later treatment (0.51). Additionally, patients treated with first-line Ocrevus had lower hospitalization rates within one year compared with patients treated with second-line or later Ocrevus (0.02 vs. 0.042, respectively).

Costs were also lower after first-line Ocrevus treatment, including the total annual non-DMT costs ($18,389 vs. $26,225, respectively) and MS-related/non-DMT costs ($8,837 vs. $14,758, respectively) compared with patients treated with second-line or later Ocrevus. Non-DMT costs were defined as total costs for emergency department visits, inpatient care, outpatient care and non-DMT prescriptions. MS-related costs were defined similarly but could also be attributed to the disease.

The findings from the study suggest that the early initiation of Ocrevus, instead of escalation from lower-efficacy DMTs, can provide benefits for both patients and the healthcare system. These clinical and economic analyses were performed on U.S. commercial claims data between January 1, 2015 and June 30, 2021.

Long-term safety from Ocrevus clinical trials consistent for nine years

New safety data as of November 2021 will be presented, representing 5,848 patients with RMS and PPMS and 25,153 patient-years of exposure to Ocrevus, across all Ocrevus clinical trials. These findings further demonstrate the consistently favorable benefit-risk profile of Ocrevus over nine years.

“Nine-year data presented at ECTRIMS in RMS and PPMS continue to show significant efficacy against disease activity and progression with a consistent long-term safety profile, which is very encouraging for patients living with this disease and their physicians,” said Stephen Hauser, M.D., chair of the Scientific Steering Committee of the OPERA studies and director of the Weill Institute for Neurosciences at the University of California, San Francisco. “Ocrevus has significantly changed the treatment paradigm for more than 250,000 people with MS since its approval more than five years ago.”

More than 250,000 people with MS have now been treated with Ocrevus globally, and data continue to show a consistent and favorable benefit-risk profile in clinical trial and real-world settings. Ocrevus is approved in 101 countries across North America, South America, the Middle East, Eastern Europe, as well as in Australia, Switzerland, the United Kingdom and the EU.

Genentech safety data do not suggest increased risk of adverse pregnancy and infant outcomes in women treated with Ocrevus

As of March 31, 2022, 2,020 cumulative MS pregnancies were reported, of which 705 (35%) had in utero exposure to Ocrevus.

Of the 532 pregnancies with in utero exposure of Ocrevus that were also prospectively reported, 286 had known outcomes: 79% live births; 1% ectopic pregnancies; 12% therapeutic/elective abortions; 8% spontaneous abortions; 0.3% still birth.

In women living with MS and treated with Ocrevus who reported pregnancies, cumulative data do not suggest an increased risk of preterm birth, major congenital anomalies or other adverse outcomes and are consistent with epidemiological data, and in-line with previous reports, providing important information for women living with MS who are or may become pregnant.

Regulatory agencies advise the use of contraception while on treatment with Ocrevus, and for 6-12 months after the last dose. The benefit-risk of Ocrevus in mothers and infants is being prospectively assessed in two Phase IV studies, MINORE in pregnant women and SOPRANINO in lactating women, both of which are currently enrolling.

About multiple sclerosis (MS)

Multiple sclerosis (MS) is a chronic disease that affects nearly one million people in the United States. MS occurs when the immune system abnormally attacks the insulation and support around nerve cells (myelin sheath) in the central nervous system (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.

People with all forms of MS experience disease progression – permanent loss of nerve cells in the central nervous system and gradual worsening of disability – at the beginning of their disease even if their clinical symptoms aren’t apparent or don’t appear to be getting worse. Delays in diagnosis and treatment can negatively impact people with MS, both in terms of their physical, mental and financial health. An important goal of treating MS is to slow the progression of disability as early as possible.

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% 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% of people with MS are diagnosed with the primary progressive form of the disease. Until the U.S. Food and Drug Administration (FDA) approval of Ocrevus, there had been no FDA-approved treatments for PPMS.

About Ocrevus^® (ocrelizumab)

Ocrevus is the first and only therapy approved for both RMS (including RRMS and active, or relapsing, secondary progressive MS [SPMS], in addition to clinically isolated syndrome [CIS] in the United States) and PPMS. 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.

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 heart beat

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. Infections are a common side effect, which can be serious. 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. Signs of herpes 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 immunoglobulins. 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 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.
  • Pregnancy Registry. There is a pregnancy registry for women who take Ocrevus during pregnancy. If you become pregnant while receiving Ocrevus, tell your healthcare provider right away. Talk to your healthcare provider about registering with the Ocrevus Pregnancy Registry. The purpose of this registry is to collect information about your health and your baby’s health. Your healthcare provider can enroll you in this registry by calling 1-833-872-4370 or visiting http://www.ocrevuspregnancyregistry.com.
• 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

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 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 ground-breaking 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, Alzheimer’s disease, Parkinson’s disease 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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