South San Francisco, CA June 23, 2017 Genentech Press Release
- OCREVUS increased the number of patients with relapsing MS (RMS) and primary progressive MS (PPMS) who maintained No Evidence of Progression or Active Disease (NEPAD) versus Rebif® (interferon beta-1a) in RMS and placebo in PPMS
- OCREVUS significantly reduced the risk of RMS and PPMS patients’ requiring mobility aids versus comparators
- In PPMS patients, OCREVUS reduced the risk of more severe forms of disability progression versus placebo
SOUTH SAN FRANCISCO, CA — 2017-06-22 00:00:00
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|
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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 OCREVUSTM (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.
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.
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.