Market Overview

New Data at EAN Show Genentech's Ocrevus (Ocrelizumab) Significantly Reduced Multiple Measures of Disease Progression in Relapsing and Primary Progressive Multiple Sclerosis

Share:





Genentech, a member of the Roche Group ((SIX: RO, ROG, OTCQX:RHHBY),
announced today that new post-hoc analyses from the OCREVUSTM
(ocrelizumab) Phase III clinical trial program in people with relapsing
and primary progressive forms of multiple sclerosis (RMS and PPMS) will
be presented at the 3rd Congress of the European Academy of Neurology
(EAN) from June 24 to June 27 in Amsterdam, Netherlands.

OCREVUS significantly reduced disease activity and disability
progression in patients with RMS and PPMS, as measured by No Evidence of
Progression or Active Disease (NEPAD), a novel composite endpoint in MS.
In RMS, OCREVUS significantly increased the proportion of patients
maintaining NEPAD by 82 percent compared with Rebif®
(interferon beta-1a) at 96 weeks in a pooled exploratory analysis of the
Phase III OPERA I and II studies (p<0.0001). In PPMS patients, OCREVUS
more than tripled the proportion of those who maintained NEPAD compared
with placebo at 120 weeks in an exploratory analysis of the Phase III
ORATORIO study (29.9 percent with OCREVUS versus 9.4 percent with
placebo, p<0.001).

NEPAD is considered a clinically meaningful endpoint because it
signifies a patient has no relapses, no confirmed disability progression
measured by the Expanded Disability Status Scale (EDSS), no progression
equal to or above 20 percent on the timed 25-foot walk (T25-FW) and the
nine-hole peg test (9-HPT), no gadolinium-enhancing T1 MRI lesions and
no new or enlarging T2 MRI lesions.

"These results underline that the significant effects of OCREVUS on
disability progression are clinically meaningful," said Ludwig Kappos,
M.D., Chair of the Department of Neurology, University Hospital, Basel,
Switzerland. "Slowing disability progression, or preventing people with
MS from having to use a cane or wheelchair, makes a great difference to
their daily lives. It is particularly exciting to see these benefits in
people with PPMS, a disabling form of MS without approved treatments in
Europe."

In separate post-hoc analyses of the OPERA I and II studies, OCREVUS
significantly reduced the risk of patients with RMS losing the ability
to walk long distances unassisted (EDSS ≥4) or requiring a cane or
crutch (EDSS ≥6) compared with interferon beta-1a at 96 weeks (p≤0.005).
In the ORATORIO study, OCREVUS significantly reduced the risk of
becoming wheelchair-bound (EDSS ≥7) compared with placebo at 120 weeks
in PPMS patients with baseline EDSS ≤6 (p≤0.028).

Furthermore, in a post-hoc analysis of the placebo-controlled ORATORIO
study, OCREVUS consistently reduced the risk of 12- and 24-week
confirmed disability progression (CDP) across three different
definitions of the measure meant to capture more severe disability
worsening than traditionally assessed in PPMS patients.

In addition, interim results from FLOODLIGHT, a sensor-based digital
monitoring study to determine adherence and correlation with in-clinic
testing in people with and without MS, will be presented. Pregnancy
outcomes in all female patients treated with OCREVUS will also be
presented.

The most common side effects associated with OCREVUS in all Phase III
studies were infusion reactions and upper respiratory tract infections,
which were mostly mild to moderate in severity.

Leading investigators will present the following oral and poster
presentations:

     
Abstract Title  

Abstract Number (type), Presentation Date, Time

Evaluation of No Evidence of Progression or Active Disease (NEPAD)
in Patients With Relapsing Multiple Sclerosis in the OPERA I and
OPERA II Trials
  PR1092 (e-presentation), Saturday, June 24, 1:30 p.m. CET
An Exploratory Analysis of the Risk of Being Restricted to
Wheelchair in Patients With Primary Progressive Multiple Sclerosis
in the ORATORIO Trial
  PR1087 (e-presentation), Saturday, June 24, 1:30 p.m. CET
Impact of Ocrelizumab on Reducing More Severe Disability Progression
in Primary Progressive Multiple Sclerosis
  O1216 (oral presentation), Saturday, June 24, 4:45 p.m. CET
A Prospective Pilot Study (FLOODLIGHT) to Evaluate the Feasibility
of Conducting Remote Patient Monitoring With the Use of Digital
Technology in Patients With Multiple Sclerosis
  EP2169 (e-poster), Sunday, June 25, 12:30 p.m. CET
Pregnancy Outcomes Following Ocrelizumab Treatment in Patients With
Multiple Sclerosis and Other Autoimmune Diseases
  EP2172 (e-poster), Sunday, June 25, 12:30 p.m. CET
Evaluation of No Evidence of Progression or Active Disease (NEPAD)
in Patients With Primary Progressive Multiple Sclerosis in the
ORATORIO Trial
  PR2086 (e-presentation), Sunday, June 25, 1:30 p.m. CET
Reduction in Progression to Disability Milestones by Ocrelizumab in
Patients With Relapsing Multiple Sclerosis: An Exploratory Analysis
of Pooled OPERA I and OPERA II Studies
  PR2079 (e-presentation), Sunday, June 25, 1:30 p.m. CET
 

Follow Genentech on Twitter via @genentech and keep up to date with EAN
2017 news and updates by using the hashtag #EAN2017.

OCREVUS is approved for use in the U.S. The OCREVUS Marketing
Authorization Application (MAA) has been validated by the European
Medicines Agency (EMA) and is currently under review.

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 now,
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 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 41 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.

View Comments and Join the Discussion!