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New OCREVUS (Ocrelizumab) Data at AAN Demonstrate Significant Reductions in Disease Activity and Disability Progression in Relapsing Multiple Sclerosis

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  • Four years of continuous treatment with OCREVUS showed a sustained
    reduction in underlying disease activity in relapsing MS (RMS) in
    analysis from the open-label extension period
  • Additional analyses show OCREVUS delayed cognitive decline and
    improved cognitive function in RMS, as measured by Symbol Digit
    Modalities Test
  • OCREVUS reduced the presence of nerve damage and inflammation
    biomarkers in people with RMS shown in interim data from a Phase III
    study
  • New safety data are consistent with OCREVUS' favorable benefit-risk
    profile for both RMS and primary progressive MS
  • Over 40,000 patients treated with OCREVUS globally

Genentech, a member of the Roche Group ((SIX: RO, ROG, OTCQX:RHHBY),
announced today that new OCREVUS® (ocrelizumab) data were
presented at the 70th American Academy of Neurology (AAN)
Annual Meeting from April 21-27 in Los Angeles, California. The data
showcase the efficacy of OCREVUS in relapsing multiple sclerosis (RMS)
through several measures of underlying disease activity and disability
progression, including magnetic resonance imaging (MRI), cognitive
function, and spinal fluid biomarkers of inflammation and
neurodegeneration. New safety data remain consistent with OCREVUS'
favorable benefit-risk profile in both relapsing and primary progressive
multiple sclerosis (PPMS).

"The OCREVUS data shared at AAN show the impact of this targeted B cell
therapy on slowing disability progression in MS, and further support the
approach of early treatment. In the extension studies, patients who
received OCREVUS continuously experienced less disease progression than
those who began treatment at a later time point," 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. "It is encouraging that with up to four years of data, we
continue to see a robust effect and a consistent safety profile."

After four years of continuous treatment, the benefits of OCREVUS in
reducing underlying disease activity in RMS were sustained, as shown in
a platform presentation measuring brain MRI activity through the
randomized and open-label extension (OLE) periods of the Phase
III studies. Patients who stayed on OCREVUS maintained low numbers of T1
gadolinium-enhancing (T1Gd+) lesions (0.017 pre-OLE to 0.17 T1Gd+
lesions per scan at year four [year two of the OLE phase]) and
new/enlarging T2 (N/ET2) lesions [0.052 pre-OLE to 0.080 N/ET2 lesions
per scan] through year two of the OLE phase. Patients who switched from
Rebif® (interferon beta-1a) to OCREVUS at the start of the
OLE period had a near-complete silencing of T1Gd+ lesions per scan at
one and two years (0.476 pre-OLE to 0.007 and 0.004 T1Gd+ lesions per
scan), as well as an 85 and 97 percent decrease in N/ET2 lesions per
scan at years one and two, respectively (2.159 pre-OLE to 0.333 and
0.063 N/ET2 lesions per scan).

A second four-year analysis presented in a poster at AAN showed people
who stayed on OCREVUS through year two of the OLE period sustained low
annualized relapse rates (ARR) and 24-week confirmed disability
progression (CDP24). Those who switched from interferon beta-1a to
OCREVUS experienced a significant decline in ARR by year one that was
maintained through year two.

New cognitive performance data, also shared in a platform presentation,
showed OCREVUS reduced the risk of 12- and 24-week confirmed cognitive
decline (as defined by confirmed worsening on the Symbol Digit
Modalities Test [SDMT] of at least four points) by 38 and 39 percent
(p≤0.001 and p=0.002, respectively) during the 96-week period in people
with RMS, compared to interferon beta-1a. Cognitive impairment occurs in
up to 65 percent of people with multiple sclerosis.1

In a separate presentation of pooled OPERA I and OPERA II data, people
with RMS at increased risk of progressive disease (as determined by
baseline Expanded Disability Status Scale [EDSS] and pyramidal Kurtzke
Functional Systems scores of at least four and two points, respectively)
and treated with OCREVUS experienced a significant improvement in
cognitive function compared with those taking interferon beta-1a through
96 weeks (measured as percent achieving ≥4 point improvement in SDMT;
62.2% vs. 46.5%; p=0.009).

"Preserving cognitive function is an important treatment goal in MS as
it relates to information processing, problem solving and focusing in
day-to-day life," said Stanley Cohan, M.D., Ph.D., Medical Director of
Providence Multiple Sclerosis Center, Portland, Oregon. "These data,
which show that OCREVUS not only delayed onset of documented cognitive
decline, but may also improve cognitive function in people with multiple
sclerosis, support a potential role for this therapy in addressing one
of the most important, common and challenging realities of multiple
sclerosis-induced disability."

Also in a platform presentation, OCREVUS was shown at 12 and 24 weeks to
reduce the presence of nerve damage and inflammation biomarkers in
spinal fluid (cerebrospinal fluid or CSF), including median
concentration of neurofilament light chain (Nf-L) (week 12: −24%, week
24: −47%) and median number of CD19+ B cells (week 12: −86%, week 24:
−82%), respectively. This interim analysis in RMS patients from the new,
Phase III Ocrelizumab Biomarker Outcome Evaluation (OBOE) study adds to
the field's body of evidence around key multiple sclerosis biomarkers,
which may be used in future research to more rapidly measure new disease
activity and how patients are responding to different therapies.

New safety data presented at AAN representing 3,778 RMS and PPMS
patients and 9,474 patient years of exposure to OCREVUS, across all
OCREVUS clinical trials, remain consistent with the medicine's favorable
benefit-risk profile. As of April 2018, over 40,000 people have been
treated globally with OCREVUS.

OCREVUS is now approved in over 55 countries across North America, South
America, the Middle East, Eastern Europe, as well as in Australia,
Switzerland and the European Union. Marketing applications are currently
under review in more than 20 countries across the world.

Full session details and data presentation listings for the 2018 AAN
Annual Meeting can be found at the meeting website: https://www.aan.com/conferences-community/annual-meeting/.

Follow Genentech on Twitter via @Genentech and keep up to date with AAN
2018 Annual Meeting news and updates by using the hashtag #AANAM.

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 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.

1 v Rahn, K., Slusher, B., Kaplin, A. Cognitive Impairment in
Multiple Sclerosis: A Forgotten Disability Remembered. Cerebrum.
2012 Nov-Dec; 2012: 14.

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