Positive Phase III Results of Genentech’s Investigational Medicine OCREVUS™ (Ocrelizumab) Published
in New England Journal of Medicine
- OCREVUS is the first and only investigational medicine to show superior efficacy versus comparators
in both relapsing and primary progressive multiple sclerosis in clinical studies
- OCREVUS demonstrated a favorable safety profile in three large Phase III studies
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) announced today that data from three Phase III studies of
its investigational medicine OCREVUS™ (ocrelizumab) – the OPERA I and OPERA II studies in relapsing multiple sclerosis (RMS) and
the ORATORIO study in primary progressive multiple sclerosis (PPMS) – were published in the December 21, 2016 online issue of the
New England Journal of Medicine (NEJM).
Data from the OCREVUS Phase III studies showed consistent and clinically meaningful reductions in major markers of disease
activity and progression compared with Rebif® (interferon beta-1a) in RMS and with placebo in PPMS. The primary endpoint
was met in all three studies, which includes relative reduction of annualized relapse rate in the RMS studies and relative
reduction in the progression of clinical disability sustained for at least 12 weeks in the PPMS study. Key secondary endpoints in
all three studies were also met, including multiple measures of disability progression and brain lesion activity.
“These publications that indicate that B cells play a central role in MS are the result of a longstanding collaboration between
the scientific community and industry for the benefit of people with MS,” 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. “In the OPERA I and OPERA II RMS studies, OCREVUS consistently and significantly
reduced disease activity and disability progression compared with a standard-of-care high-dose interferon while demonstrating a
favorable safety profile. The consistency of these pioneering data, the effect seen in these clinical studies and the favorable
safety profile may support treating MS earlier with a high-efficacy disease-modifying medicine.”
Data from two identical studies (OPERA I and OPERA II) in RMS showed OCREVUS was superior to high-dose Rebif (interferon
beta-1a), a well-established MS therapy, in reducing three major markers of disease activity: relapses (primary endpoint),
disability progression and brain lesion activity over the two-year controlled treatment period.
In a separate PPMS study (ORATORIO), OCREVUS significantly reduced the risk of confirmed disability progression sustained for at
least 12 weeks (primary endpoint) and 24 weeks (a key secondary endpoint) compared with placebo. OCREVUS treatment was also
superior to placebo on other key measures of disease progression in PPMS patients including the time required to walk 25 feet, the
volume of chronic brain lesions and brain volume loss.
“OCREVUS is the first and only investigational medicine to significantly reduce the progression of physical disability in
primary progressive MS in a large Phase III study,” said Xavier Montalban, M.D., Ph.D., Chair of the Scientific Steering Committee
of the ORATORIO study and Professor of Neurology and Neuroimmunology at Vall d’Hebron University Hospital, Research Institute and
Cemcat, Barcelona, Spain. “Over the last decade, other molecules have tried and failed to demonstrate efficacy for PPMS, so the
positive results for OCREVUS mark an important step in our understanding of this highly disabling form of the disease.”
The OCREVUS safety profile was evaluated in the three Phase III studies. In the RMS studies, the proportion of patients with
serious adverse events and serious infections was similar between the OCREVUS and interferon beta-1a treatment groups. In the PPMS
study, the proportion of patients with adverse events and serious adverse events was similar between the OCREVUS and placebo
treatment groups. Safety analyses continue in the open-label extension studies in both RMS and PPMS.
Marketing applications for OCREVUS, submitted for RMS and PPMS, have been accepted and are currently under review by the
European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA). As previously announced, OCREVUS was granted
Priority Review Designation by the FDA with a targeted action date of March 28, 2017.
OCREVUS™ is the proprietary name submitted to the FDA for the investigational medicine ocrelizumab.
About the OPERA I and OPERA II studies in RMS
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. The primary and
key secondary endpoints were previously presented at the 2015 congress of the European Committee for Treatment and Research in
Multiple Sclerosis (ECTRIMS).
Data from the Phase III OPERA studies in patients with RMS showed:
- A 46 percent and 47 percent relative reduction in the annualized relapse rate (ARR) compared with
interferon beta-1a over the two-year period in OPERA I and OPERA II, respectively (p<0.001 and p<0.001).
- A 43 percent and 37 percent relative risk reduction in confirmed disability progress (CDP) sustained
for 12 weeks compared with interferon beta-1a in OPERA I and OPERA II, respectively, as measured by the Expanded Disability
Status Scale (EDSS) (p=0.01 and p=0.02).
- A 43 percent and 37 percent relative risk reduction in CDP sustained for 24 weeks compared with
interferon beta-1a in OPERA I and OPERA II, respectively (p=0.03 and p=0.04).
- A 94 percent and 95 percent relative reduction in the total number of T1 gadolinium-enhancing lesions
compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.001 and p<0.001).
- A 77 percent and 83 percent relative reduction in the total number of new and/or enlarging
hyperintense T2 lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.001 and p<0.001).
As previously reported at the 2016 American Academy of Neurology Annual Meeting (AAN), OCREVUS increased the proportion of
patients who achieved no evidence of disease activity (NEDA) by 64 percent and 89 percent compared with interferon beta-1a at 96
weeks in OPERA I and OPERA II, respectively (p<0.001 and p<0.001). The exploratory endpoint is based on a combination of
three major markers of disease activity (relapses, disability progression and inflammatory and chronic MRI activity) and provides a
more comprehensive measurement of disease activity and the effect of treatment than any single endpoint.
Overall, the proportion of patients in the OCREVUS group with adverse events was similar to interferon beta-1a in both studies
(80.1 percent in the OCREVUS group vs. 80.9 percent in the interferon beta-1a group in OPERA I and 86.3 percent in the OCREVUS
group vs. 85.6 percent in the interferon beta-1a group in OPERA II); the most common adverse event associated with OCREVUS was
infusion-related reactions (34.3 percent of patients who received OCREVUS experienced at least one infusion-related reaction vs.
9.9 percent for interferon beta-1a). The proportion of patients in the OCREVUS group with serious adverse events, including serious
infections, was also similar to interferon beta-1a (6.9 percent in the OCREVUS group vs. 7.8 percent in the interferon beta-1a
group in OPERA I and 7.0 percent in the OCREVUS group vs. 9.6 percent in the interferon beta-1a group in OPERA II).
About the ORATORIO study in PPMS
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 PPMS. In contrast to the OPERA I and OPERA II studies, where the blinded treatment period was two years, the
blinded treatment period of the ORATORIO study continued beyond that 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. The
primary and key secondary endpoints were previously presented at the 2015 congress of ECTRIMS.
Data from the Phase III ORATORIO study in patients with PPMS showed:
- A 24 percent relative risk reduction in CDP sustained for at least 12 weeks compared with placebo, as
measured by the EDSS (p=0.03).
- A 25 percent relative risk reduction in CDP sustained for at least 24 weeks compared with placebo
(p=0.04).
- A 29 percent relative reduction in the time required to walk 25 feet (Timed 25-Foot Walk) compared
with placebo over 120 weeks (p=0.04).
- A 3.4 percent reduction in the total volume of brain hyperintense T2 lesions compared with a 7.4
percent increase in placebo-treated patients over 120 weeks (p<0.001).
- A 17.5 percent relative reduction in the rate of whole brain volume loss compared with placebo from
week 24 to week 120 (p=0.02).
Overall, the proportion of patients in the OCREVUS group with adverse events was similar to placebo (95.1 percent vs. 90.0
percent, respectively); the most common adverse event associated with OCREVUS was infusion-related reactions (39.9 percent vs. 25.5
percent for placebo). The proportion of patients in the OCREVUS group with serious adverse events, including serious infections,
was also similar to placebo (20.4 percent vs. 22.2 percent, respectively).
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.
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.
Approximately 95 percent of people with MS have a relapsing form or primary progressive MS at diagnosis. 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. Over time, some people with RRMS experience steadily worsening symptoms and transition to
secondary progressive MS (SPMS), with or without relapses. 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 10-15
percent of 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 http://www.gene.com.
All trademarks used or mentioned in this release are protected by law. Rebif is a registered trademark of Merck KGaA and
EMD Serono, Inc.
Genentech
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