Sunday, Apr 22, 2018

New OCREVUS (Ocrelizumab) Data at AAN Demonstrate Significant Reductions in Disease Activity and Disability Progression in Relapsing Multiple Sclerosis

  • Four years of continuous treatment with OCREVUS showed a sustained reduction in underlying disease activity in relapsing MS (RMS) in analysis from the open-label extension period
  • Additional analyses show OCREVUS delayed cognitive decline and improved cognitive function in RMS, as measured by Symbol Digit Modalities Test
  • OCREVUS reduced the presence of nerve damage and inflammation biomarkers in people with RMS shown in interim data from a Phase III study
  • New safety data are consistent with OCREVUS’ favorable benefit-risk profile for both RMS and primary progressive MS
  • Over 40,000 patients treated with OCREVUS globally

South San Francisco, CA -- April 22, 2018 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that new OCREVUS® (ocrelizumab) data were presented at the 70th American Academy of Neurology (AAN) Annual Meeting from April 21-27 in Los Angeles, California. The data showcase the efficacy of OCREVUS in relapsing multiple sclerosis (RMS) through several measures of underlying disease activity and disability progression, including magnetic resonance imaging (MRI), cognitive function, and spinal fluid biomarkers of inflammation and neurodegeneration. New safety data remain consistent with OCREVUS’ favorable benefit-risk profile in both relapsing and primary progressive multiple sclerosis (PPMS).

“The OCREVUS data shared at AAN show the impact of this targeted B cell therapy on slowing disability progression in MS, and further support the approach of early treatment. In the extension studies, patients who received OCREVUS continuously experienced less disease progression than those who began treatment at a later time point,” 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. “It is encouraging that with up to four years of data, we continue to see a robust effect and a consistent safety profile.”

After four years of continuous treatment, the benefits of OCREVUS in reducing underlying disease activity in RMS were sustained, as shown in a platform presentation measuring brain MRI activity through the randomized and open-label extension (OLE) periods of the Phase III studies. Patients who stayed on OCREVUS maintained low numbers of T1 gadolinium-enhancing (T1Gd+) lesions (0.017 pre-OLE to 0.17 T1Gd+ lesions per scan at year four [year two of the OLE phase]) and new/enlarging T2 (N/ET2) lesions [0.052 pre-OLE to 0.080 N/ET2 lesions per scan] through year two of the OLE phase. Patients who switched from Rebif® (interferon beta-1a) to OCREVUS at the start of the OLE period had a near-complete silencing of T1Gd+ lesions per scan at one and two years (0.476 pre-OLE to 0.007 and 0.004 T1Gd+ lesions per scan), as well as an 85 and 97 percent decrease in N/ET2 lesions per scan at years one and two, respectively (2.159 pre-OLE to 0.333 and 0.063 N/ET2 lesions per scan).

A second four-year analysis presented in a poster at AAN showed people who stayed on OCREVUS through year two of the OLE period sustained low annualized relapse rates (ARR) and 24-week confirmed disability progression (CDP24). Those who switched from interferon beta-1a to OCREVUS experienced a significant decline in ARR by year one that was maintained through year two.

New cognitive performance data, also shared in a platform presentation, showed OCREVUS reduced the risk of 12- and 24-week confirmed cognitive decline (as defined by confirmed worsening on the Symbol Digit Modalities Test [SDMT] of at least four points) by 38 and 39 percent (p≤0.001 and p=0.002, respectively) during the 96-week period in people with RMS, compared to interferon beta-1a. Cognitive impairment occurs in up to 65 percent of people with multiple sclerosis.1

In a separate presentation of pooled OPERA I and OPERA II data, people with RMS at increased risk of progressive disease (as determined by baseline Expanded Disability Status Scale [EDSS] and pyramidal Kurtzke Functional Systems scores of at least four and two points, respectively) and treated with OCREVUS experienced a significant improvement in cognitive function compared with those taking interferon beta-1a through 96 weeks (measured as percent achieving ≥4 point improvement in SDMT; 62.2% vs. 46.5%; p=0.009).

“Preserving cognitive function is an important treatment goal in MS as it relates to information processing, problem solving and focusing in day-to-day life,” said Stanley Cohan, M.D., Ph.D., Medical Director of Providence Multiple Sclerosis Center, Portland, Oregon. “These data, which show that OCREVUS not only delayed onset of documented cognitive decline, but may also improve cognitive function in people with multiple sclerosis, support a potential role for this therapy in addressing one of the most important, common and challenging realities of multiple sclerosis-induced disability.”

Also in a platform presentation, OCREVUS was shown at 12 and 24 weeks to reduce the presence of nerve damage and inflammation biomarkers in spinal fluid (cerebrospinal fluid or CSF), including median concentration of neurofilament light chain (Nf-L) (week 12: −24%, week 24: −47%) and median number of CD19+ B cells (week 12: −86%, week 24: −82%), respectively. This interim analysis in RMS patients from the new, Phase III Ocrelizumab Biomarker Outcome Evaluation (OBOE) study adds to the field’s body of evidence around key multiple sclerosis biomarkers, which may be used in future research to more rapidly measure new disease activity and how patients are responding to different therapies.

New safety data presented at AAN representing 3,778 RMS and PPMS patients and 9,474 patient years of exposure to OCREVUS, across all OCREVUS clinical trials, remain consistent with the medicine’s favorable benefit-risk profile. As of April 2018, over 40,000 people have been treated globally with OCREVUS.

OCREVUS is now approved in over 55 countries across North America, South America, the Middle East, Eastern Europe, as well as in Australia, Switzerland and the European Union. Marketing applications are currently under review in more than 20 countries across the world.

Full session details and data presentation listings for the 2018 AAN Annual Meeting can be found at the meeting website: https://www.aan.com/conferences-community/annual-meeting/.

Follow Genentech on Twitter via @Genentech and keep up to date with AAN 2018 Annual Meeting news and updates by using the hashtag #AANAM.

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 and 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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1 v Rahn, K., Slusher, B., Kaplin, A. Cognitive Impairment in Multiple Sclerosis: A Forgotten Disability Remembered. Cerebrum. 2012 Nov-Dec; 2012: 14.