Thursday, Oct 26, 2017

New OCREVUS (Ocrelizumab) Data at ECTRIMS Advance Clinical Understanding of Underlying Progression in Multiple Sclerosis

  • Data show superiority of OCREVUS compared to Rebif (interferon beta-1a) in significantly reducing disability Progression Independent of Relapse Activity (PIRA) in people with relapsing multiple sclerosis (RMS)
  • Data demonstrates first method to automatically detect and characterize Slowly Evolving Lesions (SELs) as a potential measure of underlying disease activity in the brain using MRI
  • New results from FLOODLIGHT study suggest smartphone-based disease progression monitoring can augment in-clinic tests, such as hand/arm function and walking behavior

South San Francisco, CA -- October 26, 2017 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that new OCREVUS® (ocrelizumab) data are being presented at the 7th Joint European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) – Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Meeting in Paris, France. The data presented showcase clinical advances around underlying disease activity and disability progression in relapsing and progressive forms of multiple sclerosis (MS), through the exploration of newly emerging endpoints and precision monitoring.

OCREVUS significantly reduced the proportion of people with RMS who experienced Progression Independent of Relapse Activity (PIRA) in a post-hoc analysis compared to Rebif® (interferon-beta 1a). This effect was particularly seen in those who were potentially at higher risk of progressive disease course based on their baseline Expanded Disability Status Scale (EDSS). Specifically, in this analysis, OCREVUS treatment reduced the risk of PIRA by 25 percent and 23 percent confirmed at 12 and 24 weeks, respectively (p=0.008 and p=0.039, respectively).

PIRA is a newly emerging MS endpoint intended to measure an increase in disability, which is related to underlying disease activity in RMS. These data were generated through a post-hoc analysis of more than 1,600 people randomly assigned to treatment in OPERA I and OPERA II, and assessed for PIRA, as measured by cCDP. cCDP is a measure of the risk of a person’s physical disability getting worse and is based on three measures of physical disability – confirmed disability progression, walking speed and upper extremity function.

“These new analyses of data from the large controlled studies with OCREVUS help advance our understanding of how, in relapsing MS, the disease may progress independent of relapses. These insights have implications for daily decisions made together with patients,” said Ludwig Kappos, M.D., chair of the Department of Neurology, University Hospital, Basel, Switzerland. “Even without experiencing relapses, people with RMS may still have underlying disease activity, which can cause irreversible decline in their mobility and day-to-day quality of life. Recognizing and understanding this process supports early indication of more efficacious treatment.”

A platform presentation, also highlighting underlying disease activity, showed that a new algorithm using conventional MRI can be used as a possible biomarker to automatically detect Slowly Evolving Lesions (SELs), as a potential measure of chronic disease activity outside of acute lesions in the brain. SELs were shown to evolve independently of acute lesions leading to enhanced focal brain tissue loss, as measured by T1 black hole evolution. Further research is needed, but this algorithm for automatic detection of SELs using conventional brain MRI may provide a marker of chronic disease activity in MS lesions.

“This new ability to detect both acute and underlying disease activity with conventional MRI may advance the way we monitor for MS progression and how we think about overall patient management,” 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. “While we’ve seen SELs can occur across MS subtypes, this finding may be particularly promising for people with primary progressive MS whose worsening of disability may be related to the presence of SELs. This study also highlights the importance of continued research in MS, not only for development of new treatments such as OCREVUS, but for the insights that are gained about the fundamental cause of this debilitating disease.”

New data from the FLOODLIGHT clinical trial program, which is designed to assess sensor-based outcomes from a series of active neurological tests and passive monitoring through the use of a smartphone is also being presented. The tool enables a continuous stream of precise, real-world MS disease progression data to be collected and analyzed using dedicated algorithms and machine learning.

Data at ECTRIMS – ACTRIMS demonstrate strong patient adherence to the FLOODLIGHT technology. Hand/arm function measured with a smartphone-based pinching test may detect subclinical impairment in those who have normal Nine-Hole Peg Test (9-HPT) performances. Turning speed measured with a smartphone-based U-Turn Test was shown to correlate with the Timed 25-Foot Walk (T25-FW) (p<0.001), and may detect subclinical activity compared to normal in-clinic performances. The data support FLOODLIGHT as a potential complement to in-clinic testing to provide a more complete and consistent picture of a patient’s disease progression.

Additionally, OPERA I, OPERA II and ORATORIO Phase III open-label extension data presented at ECTRIMS – ACTRIMS continue to show a favorable benefit-risk profile for OCREVUS.

OCREVUS has been approved for use in countries across North America, South America, the Middle East, Eastern Europe, as well as in Australia and Switzerland.

Follow Genentech on Twitter via @Genentech and keep up to date with Joint ECTRIMS – ACTRIMS Meeting news and updates by using the hashtag #MSParis2017.

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 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.

 

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