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New OCREVUS (Ocrelizumab) Data at ECTRIMS Advance Clinical Understanding of Underlying Progression in Multiple Sclerosis

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  • Data show superiority of OCREVUS compared to Rebif (interferon
    beta-1a) in significantly reducing disability Progression Independent
    of Relapse Activity (PIRA) in people with relapsing multiple sclerosis
    (RMS)
  • Data demonstrates first method to automatically detect and
    characterize Slowly Evolving Lesions (SELs) as a potential measure of
    underlying disease activity in the brain using MRI
  • New results from FLOODLIGHT study suggest smartphone-based disease
    progression monitoring can augment in-clinic tests, such as hand/arm
    function and walking behavior

Genentech, a member of the Roche Group ((SIX: RO, ROG, OTCQX:RHHBY),
announced today that new OCREVUS® (ocrelizumab) data are being presented
at the 7th Joint European Committee for Treatment and Research in
Multiple Sclerosis (ECTRIMS) – Americas Committee for Treatment and
Research in Multiple Sclerosis (ACTRIMS) Meeting in Paris, France. The
data presented showcase clinical advances around underlying disease
activity and disability progression in relapsing and progressive forms
of multiple sclerosis (MS), through the exploration of newly emerging
endpoints and precision monitoring.

OCREVUS significantly reduced the proportion of people with RMS who
experienced Progression Independent of Relapse Activity (PIRA) in a
post-hoc analysis compared to Rebif® (interferon-beta 1a). This effect
was particularly seen in those who were potentially at higher risk of
progressive disease course based on their baseline Expanded Disability
Status Scale (EDSS). Specifically, in this analysis, OCREVUS treatment
reduced the risk of PIRA by 25 percent and 23 percent confirmed at 12
and 24 weeks, respectively (p=0.008 and p=0.039, respectively).

PIRA is a newly emerging MS endpoint intended to measure an increase in
disability, which is related to underlying disease activity in RMS.
These data were generated through a post-hoc analysis of more than 1,600
people randomly assigned to treatment in OPERA I and OPERA II, and
assessed for PIRA, as measured by cCDP. cCDP is a measure of the risk of
a person's physical disability getting worse and is based on three
measures of physical disability – confirmed disability progression,
walking speed and upper extremity function.

"These new analyses of data from the large controlled studies with
OCREVUS help advance our understanding of how, in relapsing MS, the
disease may progress independent of relapses. These insights have
implications for daily decisions made together with patients," said
Ludwig Kappos, M.D., chair of the Department of Neurology, University
Hospital, Basel, Switzerland. "Even without experiencing relapses,
people with RMS may still have underlying disease activity, which can
cause irreversible decline in their mobility and day-to-day quality of
life. Recognizing and understanding this process supports early
indication of more efficacious treatment."

A platform presentation, also highlighting underlying disease activity,
showed that a new algorithm using conventional MRI can be used as a
possible biomarker to automatically detect Slowly Evolving Lesions
(SELs), as a potential measure of chronic disease activity outside of
acute lesions in the brain. SELs were shown to evolve independently of
acute lesions leading to enhanced focal brain tissue loss, as measured
by T1 black hole evolution. Further research is needed, but this
algorithm for automatic detection of SELs using conventional brain MRI
may provide a marker of chronic disease activity in MS lesions.

"This new ability to detect both acute and underlying disease activity
with conventional MRI may advance the way we monitor for MS progression
and how we think about overall patient management," said Stephen Hauser,
M.D., chair of the Scientific Steering Committee of the OPERA studies,
director of the Weill Institute for Neurosciences and chair of the
Department of Neurology at the University of California, San Francisco.
"While we've seen SELs can occur across MS subtypes, this finding may be
particularly promising for people with primary progressive MS whose
worsening of disability may be related to the presence of SELs. This
study also highlights the importance of continued research in MS, not
only for development of new treatments such as OCREVUS, but for the
insights that are gained about the fundamental cause of this
debilitating disease."

New data from the FLOODLIGHT clinical trial program, which is designed
to assess sensor-based outcomes from a series of active neurological
tests and passive monitoring through the use of a smartphone is also
being presented. The tool enables a continuous stream of precise,
real-world MS disease progression data to be collected and analyzed
using dedicated algorithms and machine learning.

Data at ECTRIMS – ACTRIMS demonstrate strong patient adherence to the
FLOODLIGHT technology. Hand/arm function measured with a
smartphone-based pinching test may detect subclinical impairment in
those who have normal Nine-Hole Peg Test (9-HPT) performances. Turning
speed measured with a smartphone-based U-Turn Test was shown to
correlate with the Timed 25-Foot Walk (T25-FW) (p<0.001), and may detect
subclinical activity compared to normal in-clinic performances. The data
support FLOODLIGHT as a potential complement to in-clinic testing to
provide a more complete and consistent picture of a patient's disease
progression.

Additionally, OPERA I, OPERA II and ORATORIO Phase III open-label
extension data presented at ECTRIMS – ACTRIMS continue to show a
favorable benefit-risk profile for OCREVUS.

OCREVUS has been approved for use in countries across North America,
South America, the Middle East, Eastern Europe, as well as in Australia
and Switzerland.

Follow Genentech on Twitter via @Genentech and keep up to date with
Joint ECTRIMS – ACTRIMS Meeting news and updates by using the hashtag
#MSParis2017.

About the OPERA I and OPERA II studies in relapsing forms of MS

OPERA I and OPERA II are Phase III, randomized, double-blind,
double-dummy, global multi-center studies evaluating the efficacy and
safety of OCREVUS (600 mg administered by intravenous infusion every six
months) compared with interferon beta-1a (44 mcg administered by
subcutaneous injection three times per week) in 1,656 people with
relapsing forms of MS. In these studies, relapsing MS (RMS) was defined
as relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS)
with relapses. A similar proportion of patients in the OCREVUS group
experienced serious adverse events and serious infections compared with
patients in the high-dose interferon beta-1a group in the RMS studies.

About the ORATORIO study in primary progressive MS

ORATORIO is a Phase III, randomized, double-blind, global multi-center
study evaluating the efficacy and safety of OCREVUS (600 mg administered
by intravenous infusion every six months; given as two 300 mg infusions
two weeks apart) compared with placebo in 732 people with primary
progressive MS (PPMS). The blinded treatment period of the ORATORIO
study continued until all patients had received at least 120 weeks of
either OCREVUS or placebo and a predefined number of confirmed
disability progression (CDP) events was reached overall in the study. A
similar proportion of patients in the OCREVUS group experienced adverse
events and serious adverse events compared with patients in the placebo
group in the PPMS study.

About multiple sclerosis

Multiple sclerosis (MS) is a chronic disease that affects an estimated
400,000 people in the U.S., 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 have 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 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 multiple sclerosis (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, and therefore 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.

OCREVUS U.S. Indication

OCREVUS is a prescription medicine used to treat adults with relapsing
or primary progressive forms of multiple sclerosis.

It is not known if OCREVUS is safe or effective in children.

Important Safety Information

Who should not receive OCREVUS?

Do not receive OCREVUS if you are a patient that has an active
hepatitis B virus (HBV) infection. Do not receive OCREVUS if you
are a patient that has had a life threatening allergic reaction to
OCREVUS. Patients should tell their healthcare provider if they have had
an allergic reaction to OCREVUS or any of its ingredients in the past.

What is the most important information about OCREVUS?

OCREVUS can cause serious side effects, including:

  • Infusion Reaction: OCREVUS can cause infusion reactions that
    can be serious and require a patient to be hospitalized. A patient
    will be monitored during the infusion and for at least 1 hour after
    each infusion of OCREVUS for signs and symptoms of an infusion
    reaction. Patients should tell their healthcare provider or nurse if
    they get any of these symptoms: itchy skin, rash, hives, tiredness,
    coughing or wheezing, trouble breathing, throat irritation or pain,
    feeling faint, fever, redness on the 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 the infusion.
    It is important that
    patients call their healthcare provider right away if they get any of
    the signs or symptoms listed above after each infusion. If a patient
    gets infusion reactions, the healthcare provider may need to stop or
    slow down the rate of the infusion.
  • Infection: OCREVUS increases a patient's risk of getting upper
    respiratory tract infections, lower respiratory tract infections, skin
    infections, and herpes infections. Patients should tell their
    healthcare provider if they 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 a
    patient has received their last dose of OCREVUS. If a patient has an
    active infection, their healthcare provider should delay treatment
    with OCREVUS until the infection is gone.
  • Progressive Multifocal Leukoencephalopathy (PML): Although no
    cases have been seen with OCREVUS treatment, PML may happen with
    OCREVUS. PML is a rare brain infection that usually leads to death or
    severe disability. Patients should tell their healthcare provider
    right away if they have any new or worsening neurologic signs or
    symptoms. These may include problems with thinking, balance, eyesight,
    weakness on one side of the body, strength, or using arms or legs.
  • Hepatitis B virus (HBV) reactivation: Before starting treatment
    with OCREVUS, a patient's healthcare provider will do blood tests to
    check for hepatitis B viral infection. If a patient has 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. A healthcare provider will
    monitor a patient if they are at risk for hepatitis B virus
    reactivation during treatment and after they stop receiving OCREVUS.
  • Weakened immune system: OCREVUS taken before or after other
    medicines that weaken the immune system could increase a patient's
    risk of getting infections.

Before receiving OCREVUS, patients should tell their healthcare
provider about all of their medical conditions, including if they:

  • have ever taken, take, or plan to take medicines that affect the
    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. A patient should receive any required vaccines at
    least 6 weeks before they start treatment with OCREVUS.
    A patient should
    not receive
    certain vaccines (called ‘live' or ‘live attenuated'
    vaccines) while being treated with OCREVUS and until their healthcare
    provider tells them that their immune system is no longer weakened;
  • are pregnant, think that they might be pregnant, or plan to become
    pregnant. It is not known if OCREVUS will harm an unborn baby.
    Patients should use birth control (contraception) during treatment
    with OCREVUS and for 6 months after the last infusion of OCREVUS;
  • are breastfeeding or plan to breastfeed. It is not known if OCREVUS
    passes into the breast milk. Patients should talk to their healthcare
    provider about the best way to feed their baby if the patient takes
    OCREVUS.

What are possible side effects of OCREVUS?

OCREVUS may cause serious side effects, including:

  • Risk of cancers (malignancies) including breast cancer.
    Patients should follow their healthcare provider's recommendations
    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.

Patients should call their doctor for medical advice about side effects. Patients
may report side effects to the FDA at (800) FDA-1088 or
http://www.fda.gov/medwatch.
Patients may also report side effects to Genentech at (888) 835-2555.

For additional safety information, please see the OCREVUS full
Prescribing Information and Medication Guide. For more information, go
to http://www.OCREVUS.com
or call 1-844-627-3887.

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. Roche has more than a
dozen investigational medicines in clinical development for diseases
that include multiple sclerosis, Alzheimer's disease, spinal muscular
atrophy, Parkinson's disease 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 or 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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