Tuesday, Sep 3, 2019

Genentech to Present Pivotal Data for Satralizumab in Neuromyelitis Optica Spectrum Disorder and Six-Year Ocrevus (Ocrelizumab) Data in Multiple Sclerosis at ECTRIMS

Investigational medicine satralizumab significantly reduces the risk of relapse in pivotal SAkuraStar monotherapy study for neuromyelitis optica spectrum disorder (NMOSD)

New data provide insights into neurofilament light chain (NfL) levels as a potential biomarker for predicting multiple sclerosis (MS) disability progression; new longer-term Ocrevus data of more than six years show reduction of disability progression in relapsing and primary progressive MS

Breadth of data reinforce Genentech's commitment to following the science to gain a better understanding of complex nervous system disorders

South San Francisco, CA -- September 3, 2019 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that new data across its neuroscience portfolio will be presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) from September 11-13 in Stockholm. Presentations include complete Phase III results from the SAkuraStar study investigating satralizumab for the treatment of neuromyelitis optica spectrum disorder (NMOSD), and new multiple sclerosis (MS) research, which provides insights into disease progression, including data from Ocrevus ® (ocrelizumab) trials that advance understanding of neurofilament light chain (NfL) levels as a potential biomarker for predicting disability outcomes. Additionally, longer-term data of more than six years to be presented continue to show consistent safety and efficacy outcomes for patients treated with Ocrevus earlier.

“Disorders of the nervous system are some of the most complex and difficult to treat, and we have increased our commitment in neuroscience to advance care and scientific understanding for conditions such as multiple sclerosis and neuromyelitis optica spectrum disorder. Data being presented at ECTRIMS include positive Phase III results for satralizumab as a monotherapy, taking a novel approach to treating neuromyelitis optica spectrum disorder, and new insights using biomarkers to identify disease progression in multiple sclerosis,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Similar to our approach with Ocrevus in multiple sclerosis, targeting B cells as a key driver of disease, we aim to offer satralizumab as a highly effective treatment option in neuromyelitis optica spectrum disorder, targeting the interleukin-6 receptor.”

About neuromyelitis optica spectrum disorder (NMOSD)

Complete pivotal data from the SAkuraStar study investigating satralizumab as a subcutaneous monotherapy compared to placebo for the treatment of NMOSD will be presented. The primary and subgroup analyses show that satralizumab significantly reduces the risk of relapse in patients who were seropositive for aquaporin-4 auto-antibodies (AQP4-IgG), as well as the overall intention-to-treat (ITT) population representative of NMOSD patients. Satralizumab also demonstrates a similar safety profile compared to placebo.

NMOSD is a rare, lifelong and debilitating autoimmune disease of the central nervous system commonly misdiagnosed as MS. It is associated with pathogenic AQP4-IgG auto-antibodies that target and damage a specific cell type, called astrocytes, resulting in inflammatory lesions of the optic nerve(s), spinal cord and brain. Through the use of a diagnostic biomarker test, the majority of people with NMOSD are identified as AQP4-IgG seropositive and tend to experience a more severe disease course; however, as many as one-third of those with NMOSD are AQP4-IgG seronegative. At ECTRIMS, two analyses of U.S. healthcare insurance claims databases will be presented that reflect the low utilization of AQP4-IgG diagnostic testing and the subsequent frequency of misdiagnosis of NMOSD patients.

Additionally, two pre-clinical in-vitro models will be presented that show satralizumab reduces the degradation of the blood brain barrier, supporting evidence of its multi-faceted mechanism of action.

About multiple sclerosis (MS)

New analyses will be presented that advance the understanding of NfL as a potential biomarker for predicting future MS disability outcomes, including data from the Phase III studies showing blood NfL levels in primary progressive MS (PPMS) and relapsing MS (RMS) patients were significantly lowered following Ocrevus treatment. NfL is a protein that provides structural support to nerve fibers in the brain, and an increase in the amount of NfL in blood serum or cerebrospinal fluid may serve as a marker for axonal (nerve) damage. Studying NfL may provide more information on how to quickly measure MS disease activity and progression. This is important because a key goal of treatment is to reduce disease activity to delay disability progression as soon as possible.

Longer-term data of more than six years from the Phase III open-label extension studies of OPERA I, OPERA II and ORATORIO showed that patients who were treated earlier with Ocrevus had lower rates of disability progression compared with RMS patients who switched from interferon beta-1α or PPMS patients who switched from placebo after the double-blind phase. Additionally, updated safety data being presented remain consistent with findings from the Phase III studies, supporting Ocrevus’ favorable benefit-risk profile.

Over 120,000 people have been treated with Ocrevus globally, both in clinical trial and real-world settings, and Ocrevus is now approved in 89 countries.

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

A full list of Genentech presentations can be found at: https://www.ectrims-congress.eu/2019/scientific-programme/scientific-programme.html .

Presentations at ECTRIMS 2019 include:

Medicine

Abstract Title

Presentation Number (type)

Presentation Date

Time

Satralizumab for Neuromyelitis Optica Spectrum Disorder

Efficacy and Safety of Satralizumab Monotherapy for Relapse Prevention in Neuromyelitis Optica Spectrum Disorder (NMOSD): Results from SAkuraStar, a Double-Blind Placebo-Controlled Phase 3 Clinical Study

#P603 (poster presentation)

Wednesday, September 11

5:15 – 7:15 PM CEST

Identifying Patients with Neuromyelitis Optica Spectrum Disorder in US Insurance Claims Databases

#P408 (poster presentation)

Wednesday, September 11

5:15 – 7:15 PM CEST

The Effect of Neuromyelitis Optica (NMO)-IgG and Anti-IL-6 Receptor Monoclonal Antibody (SA237; satralizumab) for Barrier Function at the Blood-Brain Barrier In Vitro

#P473 (poster presentation)

Wednesday, September 11

5:15 – 7:15 PM CEST

Efficacy of Satralizumab as Monotherapy in Pre-Specified Subgroups of SAkuraStar, a Double-Blind Placebo-Controlled Phase 3 Clinical Study in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD)

#141 (oral presentation)

Thursday, September 12

8:54 – 9:06 AM CEST

Temporal Trends in the Diagnosis of Neuromyelitis Optica Spectrum Disorder in US Claims Databases From 2001-2017

#P1130 (poster presentation)

Friday, September 13

12:15 – 2:15 PM CEST

Efficacy and Safety of Satralizumab for Relapse Prevention in

Neuromyelitis Optica Spectrum Disorder: A Pooled Analysis from Two Phase 3 Clinical Trials

#P1614 (poster presentation)

Friday, September 13

12:15 – 2:15 PM CEST

Anti-IL-6 Receptor Antibody Prevents Blood-Brain Barrier Disruption in Mice with Experimental Autoimmune Encephalomyelitis (EAE)

#EP1497 (ePoster) ePosters will be displayed on terminals during the congress, not presented during specific sessions.

Ocrevus (ocrelizumab) for Multiple Sclerosis

Serum Immunoglobulin Levels and Risk of Serious Infections in the Pivotal Phase III Trials of Ocrelizumab in Multiple Sclerosis and Their Open‐Label Extensions

#65 (oral presentation)

Wednesday, September 11

2:49 – 3:01 PM CEST

Effect of Ocrelizumab Versus Interferon β-1a on Retinal Thinning and Association with Brain Volume Loss in the OPERA I and OPERA II Phase III Trials in Relapsing Multiple Sclerosis

#92 (oral presentation)

Wednesday, September 11

4:37 – 4:49 PM CEST

Efficacy and Safety of Ocrelizumab in Patients with Relapsing‐Remitting Multiple Sclerosis with a Suboptimal Response to Previous Disease‐Modifying Therapies (1‐Year Interim Results)

#P690 (poster presentation)

Wednesday, September 11

5:15 – 7:15 PM CEST

Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients with Relapsing and Primary Progressive Multiple Sclerosis

#P648 (poster presentation)

Wednesday, September 11

5:15 – 7:15 PM CEST

Blood Neurofilament Light Levels are Lowered to a Healthy Donor Range in Patients with RMS and PPMS Following Ocrelizumab Treatment

#152 (oral presentation)

Thursday, September 12

9:06 – 9:18 AM CEST

Sustained Reduction in Confirmed Disability Progression in Patients with Primary Progressive Multiple Sclerosis Treated with Ocrelizumab in the Open-Label Extension Period of the Phase III ORATORIO Trial: 6.5-Study Year Follow-Up Data

#159 (oral presentation)

Thursday, September 12

11:16 – 11:28 AM CEST

Pregnancy Outcomes in Patients Treated with Ocrelizumab

#P780 (poster presentation)

Thursday, September 12

5:15 – 7:15 PM CEST

Real-World Experience with Ocrelizumab in the MS Base Registry

#P1017 (poster presentation)

Thursday, September 12

5:15 – 7:15 PM CEST

Pretreatment Cerebrospinal Fluid (CSF) and Serum Neurofilament Light (NfL) Levels in Patients with PPMS in the OBOE Study are Correlated and are Higher in Patients with PPMS with T1 Gd+ Brain Lesions

#P948 (poster presentation)

Thursday, September 12

5:15 – 7:15 PM CEST

Long-Term Reduction of Relapse Rate and Confirmed Disability Progression After 6 Years of Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis

#P1015 (poster presentation)

Thursday, September 12

5:15 – 7:15 PM CEST

Cases Reported as Progressive Multifocal Leukoencephalopathy in Ocrelizumab-Treated Patients with Multiple Sclerosis

#P970 (poster presentation)

Thursday, September 12

5:15 – 7:15 PM CEST

FlywheelMS: A Novel, Patient-Centred Study to Better Understand Multiple Sclerosis Using Electronic Health Records and Other Real-World Data Sources

#P758 (poster presentation)

Thursday, September 12

5:15 – 7:15 PM CEST

Baseline Cognitive Functioning Using the Brief International Cognitive Assessment for MS Tests in Patients with Relapsing‐Remitting Multiple Sclerosis Enrolled in Phase IIIb Studies of Ocrelizumab (ENSEMBLE and CASTING)

#P1170 (poster presentation)

Friday, September 13

12:15 – 2:15 PM CEST

Evaluation of Shorter Infusion Times for Ocrelizumab Treatment in an Extension Substudy of the Phase IIIb CHORDS Trial

#P1408 (poster presentation)

Friday, September 13

12:15 – 2:15 PM CEST

Safety Results for Administering Ocrelizumab per a Shorter Infusion Protocol in Patients with Primary Progressive and Relapsing Multiple Sclerosis

#P1406 (poster presentation)

Friday, September 13

12:15 – 2:15 PM CEST


Ocrelizumab Treatment Satisfaction in Patients with Suboptimal Response to Previous Disease-Modifying Therapies

#EP1479 (ePoster) ePosters will be displayed on terminals during the congress, not presented during specific sessions.


About satralizumab

Satralizumab is an investigational humanized monoclonal antibody that represents a novel approach to treating NMOSD. The cytokine IL-6 is thought to be a key driver of NMOSD, triggering the inflammation cascade and leading to damage and disability. Positive Phase III results for satralizumab, as both monotherapy and add-on to baseline immunosuppressant therapy, suggest that IL-6 inhibition may be an effective therapeutic approach for NMOSD.

The Phase III clinical development program for satralizumab includes two studies: SAkuraSky, which studied satralizumab in combination with baseline immunosuppressant therapy, and SAkuraStar, which studied the efficacy and safety of satralizumab as a monotherapy.

Satralizumab has been designated as an orphan drug in the United States and Europe. In addition, it was granted Breakthrough Therapy Designation for the treatment of NMO and NMOSD by the U.S. Food and Drug Administration in December 2018.

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. The company’s goal is to develop treatment options based on the biology of the nervous system to help improve the lives of people with chronic and potentially devastating diseases. Genentech and Roche have more than a dozen investigational medicines in clinical development for diseases that include multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Duchenne muscular dystrophy and autism.

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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