Phase III Efficacy Results of Investigational Medicine OCREVUS™ (Ocrelizumab) Reinforced by Exploratory Analyses in Two Forms of Multiple Sclerosis

  • 75 percent higher proportion of relapsing multiple sclerosis (RMS)
    patients achieved No Evidence of Disease Activity (NEDA) with OCREVUS
    compared with interferon beta-1a (Rebif®)
  • 47 percent higher proportion of primary progressive multiple sclerosis
    (PPMS) patients achieved No Evidence of Progression (NEP) with OCREVUS
    compared with placebo

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche group (SIX: RO, ROG; OTCQX: RHHBY),
today announced new analyses from the three OCREVUS™ (ocrelizumab) Phase
III studies in relapsing multiple sclerosis (RMS) and primary
progressive multiple sclerosis (PPMS) will be presented during the 32nd
congress of the European Committee for Treatment and Research in
Multiple Sclerosis (ECTRIMS), from September 14-17 in London, England.

OCREVUS increased disease control in patients with RMS and PPMS in
separate post-hoc analyses. In these analyses, two composite endpoints
measured disease control using a combination of clinical and MRI
outcomes: No Evidence of Disease Activity (NEDA) in patients with RMS
and No Evidence of Progression (NEP) in patients with PPMS. These
composite endpoints are emerging as new treatment targets.

A NEDA analysis of pooled data from the Phase III OPERA I and OPERA II
studies compared no evidence of disease activity during different time
periods over two years of study. NEDA is achieved when a patient has no
relapses, no confirmed disability progression, no gadolinium-enhancing
MRI lesions and no new or enlarging MRI lesions. The data showed that
OCREVUS significantly increased the proportion of RMS patients achieving
NEDA by 75 percent compared with interferon beta-1a over 96 weeks (0-96
weeks, p<0.0001). Additionally, compared with interferon beta-1a,
OCREVUS treatment significantly increased the relative proportion of
patients achieving NEDA by 33 percent in weeks 0-24 and by 72 percent in
weeks 24-96 (both p<0.0001). A majority of patients achieved NEDA in the
first 24 weeks of OCREVUS treatment (60.8 percent) and this proportion
increased during weeks 24-96 of the study (72.2 percent).

“Controlling clinical and sub-clinical disease activity as early as
possible is an important treatment goal for people living with MS,” said
Professor Gavin Giovannoni, Scientific Steering Committee Member of the
OPERA I and II studies and Chair of Neurology at Barts and The London
School of Medicine and Dentistry. “These new data suggest that
ocrelizumab consistently impacts disease progression and has the
potential to change how we approach treating both relapsing and primary
progressive MS.”

New post-hoc analyses of the ORATORIO study in PPMS patients measured
NEP, which includes three measures of physical disability (confirmed
disability progression, walking speed and upper extremity function) and
reflects no evidence of worsening of a person’s physical disability.
Patients who achieved NEP had no evidence of confirmed disability
progression sustained for at least 12 weeks and less than 20 percent
worsening of performance on the timed 25-foot walk and 9-hole peg test.
OCREVUS treatment significantly increased the proportion of PPMS
patients with NEP by 47 percent at week 120 compared with placebo

“With no approved treatment options, primary progressive MS remains a
challenge for physicians and people with MS,” said Xavier Montalban,
M.D., Ph.D., Professor of Neurology and Neuroimmunology at Vall d’Hebron
University Hospital, Research Institute and Cemcat, Barcelona, Spain.
“OCREVUS significantly impacted three key disability measurements, which
further highlight its clinical significance in people with primary
progressive MS.”

In addition, new patient-reported outcomes data from the ORATORIO study
highlighting the unmet need of people with PPMS, including the effect
OCREVUS had on fatigue measures, will be presented.

Leading investigators will present the following oral and poster

Abstract Title    

Abstract Number (type),
Presentation Date, Time

An exploratory analysis of 12- and 24-week composite confirmed
disability progression in patients with primary progressive multiple
sclerosis in the ORATORIO trial
    P746 (poster), Thursday, September 15, 3:45 – 5:00 p.m. BST
Infusion-related reactions with ocrelizumab in relapsing multiple
sclerosis and primary progressive multiple sclerosis
    P720 (poster), Thursday, September 15, 3:45 – 5:00 p.m. BST
Evaluation of no evidence of progression using composite disability
outcome measures, in patients with primary progressive multiple
sclerosis in the ORATORIO trial
    167 (oral), Friday, September 16, 9:51 – 10:03 a.m. BST
Effect of ocrelizumab on magnetic resonance imaging markers of
neurodegeneration in patients with relapsing multiple sclerosis:
analysis of the Phase III, double-blind, double-dummy, interferon
beta-1a-controlled OPERA I and OPERA II studies
    P1011 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST
Patient-reported outcomes in the Phase III double-blind,
placebo-controlled ORATORIO study of ocrelizumab in primary
progressive multiple sclerosis
    P1279 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST
Infections and serious infections with ocrelizumab in relapsing
multiple sclerosis and primary progressive multiple sclerosis
    P1248 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST
Design of two phase III open-label trials evaluating ocrelizumab in
patients with relapsing-remitting multiple sclerosis and suboptimal
response to disease-modifying treatment
    P1180 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST
Baseline assessment of fatigue and health-related quality of life in
patients with primary progressive multiple sclerosis in the ORATORIO
    P1278 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST
Exploration and verification of a patient-powered research network
to provide patient insights in multiple sclerosis
    P889 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST
NEDA epoch analysis of patients with relapsing multiple sclerosis
treated with ocrelizumab: Results from OPERA I and OPERA II, Phase
III studies
    P1593 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST
Real-world treatment observation in multiple sclerosis: development
of an online platform to measure patients’ treatment awareness and
experiences, access barriers and decision-making
    ePoster will be displayed on terminals during the congress

Follow Genentech on Twitter via @Genentech and keep up to date with
ECTRIMS 2016 news and updates by using the hashtag #ECTRIMS2016.

As previously announced, the U.S. Food and Drug Administration (FDA)
accepted for review the company’s Biologics License Application (BLA)
for OCREVUS for the treatment of RMS and PPMS, and granted the
application Priority Review Designation with a targeted action date of
December 28, 2016.

OCREVUS™ is the proprietary name submitted to the FDA for the
investigational medicine ocrelizumab.

About OCREVUS (ocrelizumab)

OCREVUS is an investigational, humanized monoclonal antibody designed to
selectively 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, and therefore important functions of
the immune system may be preserved.

The Phase III clinical development program for OCREVUS (ORCHESTRA)
includes three studies: OPERA I, OPERA II and ORATORIO. OPERA I and
OPERA II are identical Phase III, randomized, double-blind,
double-dummy, global multi-center studies that evaluated 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 (i.e., relapsing-remitting MS and
secondary-progressive MS with relapses). ORATORIO is a Phase III,
randomized, double-blind, global multi-center study that evaluated the
efficacy and safety of OCREVUS (600 mg administered by intravenous
infusion every six months) compared with placebo in 732 people with
primary progressive MS (PPMS).

The most common adverse events associated with OCREVUS were
infusion-related reactions and infections, which were mostly mild to
moderate in severity.

About multiple sclerosis

Multiple sclerosis (MS) is a chronic disease that affects an estimated
2.3 million people around the world, 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 MS is the most common form of the disease. Disease activity
and progression can occur even when people do not show signs or symptoms
of MS, despite available relapsing MS treatments. 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 one in 10 people with MS are diagnosed with the
primary progressive form of the disease. There are no approved
treatments for PPMS.

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 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

All trademarks used or mentioned in this release are protected by
law. Rebif is a registered trademark of Merck KGaA and EMD Serono, Inc.


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