Genentech presents new six-year Ocrevus (Ocrelizumab) data

Post-hoc analysis from a Phase III open-label extension study showed a 42% reduction in the risk of PPMS patients needing a wheelchair after six and a half years of Ocrevus treatment compared with patients who started Ocrevus after the double-blind period

Interim analysis of Phase IIIb study shows 87% of patients with suboptimal response to previous treatment had no evidence of disease activity one year after switching to Ocrevus

Separate analysis from same study showed greater patient satisfaction with Ocrevus after one year on treatment –

More than 120,000 people have been treated with Ocrevus globally, in clinical trial and real-world settings; data continue to show a consistent and favorable benefit-risk profile

South San Francisco, CA — September 12, 2019 —

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today longer-term data from the Phase III open-label extension studies of OPERA I, OPERA II and ORATORIO showed that patients who were treated with Ocrevus^® (ocrelizumab) continuously for six years or more had reduced risk of disability progression in relapsing MS (RMS) and primary progressive MS (PPMS). These results suggest earlier treatment with Ocrevus reduced the risk of disability progression and this effect was sustained over time. Additionally, new safety data as of January 2019 were announced, representing 4,611 patients with RMS and PPMS and 14,329 patient years of exposure to Ocrevus, across all Ocrevus clinical trials, and remain consistent with the medicine’s favorable benefit-risk profile. Findings were presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Stockholm.

“The effect of MS therapies on progression – not just relapses – is very important to help reduce the impact of the disease on the daily lives of people with MS and their families,” said Professor Gavin Giovannoni, Consultant Neurologist at Barts and the London School of Medicine and Dentistry. “The Ocrevus data at ECTRIMS highlight that the benefit of delaying, and possibly preventing, disability progression is greater when the treatment is used earlier in the disease course for both relapsing and primary progressive forms of MS. These data support the aphorism, ‘time really is brain and spinal cord in multiple sclerosis.”

In the OPERA OLE, the proportion of RMS patients with 24-week confirmed disability progression (CDP) was lower for those treated with continuous Ocrevus (total of six years on Ocrevus) compared with patients who switched to Ocrevus after two years of interferon beta-1a treatment in the double-blind period (total of four years on Ocrevus) (19% vs. 24%; p <0.05).

In the ORATORIO OLE, the proportion of PPMS patients with 24-week CDP was lower for those treated with continuous Ocrevus over six and a half years compared with patients who switched to Ocrevus from placebo after the double-blind period (52% vs. 65%; p=0.002). Upper limb disability progression, measured by the nine-hole peg test (9-HPT), was significantly reduced in patients who were continuously treated with Ocrevus compared with those who switched from placebo (31% vs. 43%; p=0.004). Data also showed earlier intervention with Ocrevus resulted in a 42% reduction in the risk of PPMS patients needing a wheelchair (EDSS≥7) over 6.5 years compared with patients who started Ocrevus treatment after the double-blind period (p=0.0112).

Additionally, data from the open-label Phase IIIb CASTING study evaluating Ocrevus in patients with RRMS who had a suboptimal response to at least six months of treatment with one or two other disease-modifying treatments (DMTs) were presented. An interim analysis showed 87% of patients who switched to Ocrevus had no evidence of disease activity (NEDA) after 48 weeks of treatment.

A new, separate analysis from the same study showed that patients who switched from another DMT to Ocrevus reported greater satisfaction with Ocrevus after one year of treatment. Patients reported satisfaction with its effectiveness, side effects, convenience and overall satisfaction, as measured by the self‐reported Treatment Satisfaction Questionnaire for Medication vII (TSQM vII).

Furthermore, results from two Phase IIIb studies, the CHORDS substudy in RRMS and the SaROD study in PPMS and RMS, demonstrate patients treated with Ocrevus at a reduced infusion time showed no increased risk of serious, severe or life-threatening infusion-related reactions. The current infusion time is approximately 3.5 hours and a majority of the patients in these studies completed infusions within 2.5 hours. Frequency of administration is highly important to patients and their healthcare providers and potentially shorter Ocrevus infusion times once every six months may improve the overall treatment experience.

In addition to consistent overall safety outcomes, new data on 267 pregnancies in MS patients from Ocrevus clinical trials and real-world use were also in line with previous reports, and the reviewed cases to date do not suggest an increased risk of adverse pregnancy outcomes in case of accidental exposure within a year of conception or during pregnancy.

Ocrevus is the first and only therapy approved for both RMS (including relapsing-remitting MS [RRMS] and active, or relapsing, secondary progressive MS, in addition to clinically isolated syndrome in the United States) and PPMS. Ocrevus is dosed every six months, with rapidly increasing real-world experience and more than 120,000 people with MS treated globally. Ocrevus is now approved in 89 countries across North America, South America, the Middle East, and Eastern Europe, as well as in Australia, Switzerland and the European Union.

Full session details and data presentation listings for ECTRIMS can be found at the congress website: https://www.ectrims-congress.eu/2019.html.

Follow Genentech on Twitter via @Genentech and keep up to date with ECTRIMS 2019 news and updates by using the hashtag #ECTRIMS2019.

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 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.