Genentech Announces New OCREVUS (Ocrelizumab) Data on Long-Term Disability Benefits in Primary Progressive Multiple Sclerosis and Initiation of Two Global Studies in Progressive MS

  • OCREVUS may delay the need for a wheelchair by seven years for people
    with primary progressive multiple sclerosis (PPMS)
  • Longer-term efficacy and safety data are consistent with OCREVUS’
    favorable benefit-risk profile for both PPMS and relapsing MS (RMS)
  • Two new Phase IIIb studies for OCREVUS in progressive MS will use
    novel endpoints to evaluate upper-limb function and disability
    progression
  • FLOODLIGHT Open, a study that uses smartphone-based technology to
    monitor MS disease progression, is now enrolling in the United States
  • OCREVUS approved in more than 60 countries, with 50,000 patients
    treated globally to date

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
announced today that new OCREVUS® (ocrelizumab) data will be
presented at the 4th Congress of the European Academy of
Neurology (EAN) from June 16-19 in Lisbon, Portugal. The new Phase III
data analyses show OCREVUS may provide meaningful disability benefits
such as delay in the need for a wheelchair for people with primary
progressive multiple sclerosis (PPMS). Genentech continues its
commitment to people with progressive forms of MS by initiating two new
global Phase IIIb studies that will evaluate the efficacy of OCREVUS in
a broad range of people with progressive forms of MS.

In a new exploratory analysis from the extended control period of the
Phase III ORATORIO study in PPMS, OCREVUS may significantly delay the
time to need a wheelchair by seven years, as measured by the length of
time until a person reaches Expanded Disability Status Scale seven or
greater (EDSS≥7) using 24-week confirmed disability progression (CDP).
People treated with OCREVUS had a 46 percent reduction in the risk of
progressing to a wheelchair compared to the placebo-treated group (6.2
percent vs. 9.8 percent risk, respectively, p=0.022). When these results
were extended (extrapolated) to calculate the median time-to-wheelchair,
the data suggest OCREVUS treatment may delay the need for a wheelchair
by seven years (19.2 years for OCREVUS vs. 12.1 years for placebo).

“To a person living with primary progressive MS, for whom disability
accumulates twice as fast as in relapsing MS, seven more years without
the need for a wheelchair could extend the time they can live
independently in their home, continue working or looking after their
families,” said Helmut Butzkueven, Professor and Chair of MS and
Neuroimmunology Research at Central Clinical School, Monash University,
Head of MS and Neuroimmunology Service at Alfred Health and Director of
MS Service at Eastern Health. “The data at EAN show the significant
impact that OCREVUS, the first disease-modifying medicine for PPMS
approved in more than 60 countries around the world, can have on people
with MS with the greatest unmet need.”

Additionally, the analysis showed that the placebo-treated patient
population studied in ORATORIO had similar disability progression rates
to an untreated real-world PPMS population. The extrapolated median time
to wheelchair (EDSS≥7) for placebo-treated people in the ORATORIO study
was 12.1 years compared to 12.4 years for people with PPMS in the
real-world MSBase registry.

Longer-term safety data presented at EAN 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 June 2018, over 50,000 people have been
treated globally with OCREVUS.

In parallel to EAN and following the success of Genentech’s first MS
Forum in 2017, Genentech will be hosting a live MS Forum: ‘Maintaining
Independence in Progressive Multiple Sclerosis’ on Monday, June 18, 4:00
– 5:00 p.m. CEST. Registration can be made here: http://livestream.videum.com/roche/ms/.

Follow Genentech on Twitter via @Genentech and keep up to date with EAN
2018 news and updates by using the hashtag #EAN2018.

OCREVUS is now approved in over 60 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.

FLOODLIGHT Open now enrolling in the U.S.

FLOODLIGHT Open is a new global study using Roche and Genentech’s
proprietary FLOODLIGHT mobile technology to collect and monitor
anonymized patient data to help gain a better understanding of MS
disease progression. The FLOODLIGHT mobile technology assesses
sensor-based outcomes from a series of active neurological tests and
passive monitoring through the use of patients’ smartphones. An ongoing
pilot study, most recently presented at the 2018 American Academy of
Neurology Annual Meeting, supports the FLOODLIGHT mobile technology as a
potential complement to in-clinic testing that may provide a more
complete and consistent picture of a patient’s underlying disease
activity and its effect on disability progression. FLOODLIGHT Open is an
observational, open access study aimed to enroll 10,000 people globally,
including people with relapsing and progressive forms of MS, within five
years. Data will be available through an open access database that is
accessible to the entire MS research community. For more information on
the FLOODLIGHT Open study and how to enroll, visit http://www.floodlightopen.com.

New progressive MS studies initiating in 2018

Many people with progressive MS eventually transition into a wheelchair,
which means that maintaining the ability to use their hands and arms is
important, especially in later stages of the disease. To advance the
clinical understanding of MS progression and the importance of
maintaining upper-limb function in people with progressive MS, Genentech
will be initiating two new Phase IIIb studies of OCREVUS in 2018.

A first-of-its-kind study, ORATORIO-HAND, will evaluate the long-term
safety and efficacy of OCREVUS in people with PPMS later in their
disease course (with an EDSS score three to eight) and the Nine-Hole Peg
Test (9-HPT) — a measure of arm, wrist and hand function — will be used
as the primary efficacy outcome. A key secondary endpoint is 12-week
CDP. This multi-center, randomized, placebo-controlled, double-blind
study is planned to start before the end of 2018 and will enroll
approximately 1,000 people with PPMS.

“Addressing the needs of people with progressive MS, who are typically
more advanced in their disease course, is one of the major frontiers in
MS research. Around a third of people living with progressive MS may
already be confined to a wheelchair, so maintaining hand and arm
function is essential for them to stay independent and lead active
lives,” said lead trial investigator Gavin Giovannoni, Professor of
Neurology at Barts and The London School of Medicine and Dentistry,
Queen Mary University of London. “For a number of years, through our
#ThinkHand campaign, we have been urging industry to conduct a study
looking at upper limb function in people with advanced MS. We’re pleased
that in collaboration with Roche and Genentech, we will conduct a
clinical trial that uses hand function as a primary outcome for the
first time.”

The second study, named CONSONANCE, will evaluate the efficacy of
OCREVUS in the complete spectrum of progressive MS (PPMS and secondary
progressive MS (SPMS)). The CONSONANCE study will measure the long-term
effectiveness of OCREVUS in progressive MS with novel composite
disability endpoints, including No Evidence of Progression (NEP) and No
Evidence of Progression or Active Disease (NEPAD), in addition to a wide
range of patient-relevant measures and advanced MRI outcomes. The
four-year, Phase IIIb study is currently enrolling 600 people with PPMS
or SPMS (in a 1:1 ratio) from across 26 countries. The study will also
explore whether technology-enabled, continuous sensor-based and
self-administered measures may detect changes in disability progression
earlier than conventional clinical measures.

Genentech presentations at EAN 2018

Leading investigators will present the following oral and poster
presentations at EAN 2018:

Abstract Title     Presentation Number (type), Presentation Date, Time
Risk of Becoming Wheelchair-Confined in Patients With Primary
Progressive Multiple Sclerosis: Data From the ORATORIO Trial and a
Long-Term Real-World Cohort From MSBase Registry
    #EPR1087 (e-presentation), Saturday, June 16, 1:30 p.m. CEST
Effect of Ocrelizumab on Relapse Rate, and Disability Progression
and Improvement in Relapsing Multiple Sclerosis Patients in the
Open-Label Extension of the Pooled OPERA Trials
    #EPR1089 (e-presentation), Saturday, June 16, 1:30 p.m. CEST
Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in
Patients With Relapsing and Primary Progressive Multiple Sclerosis
    #EPR1105 (e-presentation), Saturday, June 16, 1:30 p.m. CEST

Baseline Characteristics of the CASTING Study Population: A Phase
IIIb Trial Evaluating Ocrelizumab in Patients with
Relapsing-Remitting Multiple Sclerosis and Suboptimal Response to
Disease-Modifying Therapies

    #EPO2077 (e-poster), Sunday, June 17, 12:30 p.m. CEST
Prespecified Subgroup Analyses of Ocrelizumab Efficacy in Patients
With Primary Progressive Multiple Sclerosis from the Phase III
ORATORIO Study
    #EPR2101 (e-presentation), Sunday, June 17, 1:30 p.m. CEST
Subgroup Analyses of NEDA Re-Baselined at Week 24 in Ocrelizumab
Recipients with Relapsing Multiple Sclerosis Receiving Ocrelizumab
in OPERA I and II
    #EPR3099 (e-presentation), Monday, June 18, 1:30 p.m. CEST
Routine Laboratory Measures in the Controlled-Treatment Period of
Phase III Ocrelizumab Trials in Relapsing and Progressive Multiple
Sclerosis
    Abstract #2212 (poster on display), available throughout the congress
Effect of Ocrelizumab on Vaccine Responses in Patients With Multiple
Sclerosis
    Abstract #2215 (poster on display), available throughout the congress
Patient-Reported Fatigue in Progressive Multiple Sclerosis     Abstract #2060 (poster on display), available throughout the congress

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.

Contacts

Genentech
Media Contact:
Kimberly Muscara, 650-467-6800
or
Advocacy
Contact:
Jo Dulay, 202-316-6304
or
Investor Contact:
Loren
Kalm, 650-225-3217
Karl Mahler, 011 41 61 687 8503