OCREVUS is a first-in-class treatment that targets B-cells, offering a new pathway to treat MS1

MISSISSAUGA, ON, Aug. 15, 2017 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) today announced that Health Canada has approved OCREVUS™ (ocrelizumab) for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease defined by clinical and imaging features.2 The approval of OCREVUS is based on the pivotal phase III, OPERA I & II studies, in which safety and efficacy were evaluated. OCREVUS demonstrated superior efficacy on the three major markers of disease activity by reducing relapses per year by nearly half (46 per cent and 47 per cent form OPERA I & II, respectively), slowing the worsening of disability and significantly reducing MRI lesions compared with the standard of care (high-dose interferon beta-1a) over the two-year controlled treatment period.3

OCREVUS is designed to selectively target B-cells, a specific type of immune cell thought to be a key contributor to nerve cell damage, which leads to disability in people with MS. As demonstrated in the OPERA studies, OCREVUS binds to a protein (CD-20) found on some B-cells that would otherwise attack the protective layer around the brain's nerve fibers. At the same time, OCREVUS does not bind to stem cells or plasma cells, maintaining the capacity of B-cells to rebuild and therefore important functions of the immune system are preserved.4

According to a recent survey, 80 per cent of Canadian Neurologists hope to improve the frequency of relapses as their primary clinical goal and 78 per cent strive to improve the patient's overall quality of life (the primary non-clinical goal).5

"Ocrevus is a major addition to the treatment options available for MS. The RRMS Ocrevus clinical trial data show a significant reduction in relapses and disease progression, as well as a good safety profile," says Dr. Daniel Selchen, Neurologist and Head of the Division of Neurology at St. Michael's Hospital in Toronto. "For appropriate patients, Ocrevus will be of great value in reducing the burden of MS."

Today, there are approximately 100,000 Canadians living with MS6 and RRMS is the most common form, characterized by clearly defined attacks of new or worsening neurologic symptoms.7 In patients with MS, damaged nerves lose their ability to communicate with the rest of the body, leading to unpredictable and often debilitating symptoms such as weakness, fatigue, and vision problems,8,9,10 impacting their everyday life.

"Before Ocrevus, I had symptoms everyday, and there was always the constant hassle of worrying about how I was going to transport the MS medications whenever I traveled," says Ian Gardiner, MS patient. "Since starting the treatment, I feel so much better. I feel that it is keeping my MS in check and my MS symptoms at bay while giving me back control over my life. Due to the dosing regimen, I now have more freedom to travel without the worry of transporting my MS medication."

According to a recent Global survey of 3,478 patients and caregivers, results showed that MS significantly interferes with daily life, with 96 per cent missing out on social commitments due to symptoms or flare-ups.11 The top three symptoms with the highest impact on Canadian MS patients' everyday life are: weakness (60 per cent); pain (60 per cent); and fatigue (51 per cent).12

"The approval of Ocrevus is good news for people living with MS, as they now have one more treatment option to help manage this unpredictable disease," says Dr. Karen Lee, Vice-President of research at the Multiple Sclerosis Society of Canada. "This approval reinforces the need for ongoing research into viable MS treatments. Through continued investment in research, we can accelerate the development of innovative treatments that go through rigorous testing and can help change the prognosis for many people living with MS."

ABOUT THE HEALTH CANADA APPROVAL & OPERA STUDIES

The Health Canada approval of OCREVUS is based on the pivotal phase III, OPERA I & II studies, which are randomized, double blind, double-dummy, active comparator-controlled clinical trials with identical designs, in patients with relapsing forms of MS.13

The OPERA studies evaluated the safety and efficacy of OCREVUS (with the first dose administered as two 300 mg IV infusions separated by 2 weeks and all subsequent doses as a single, 600 mg infusion) compared with the standard of care (high-dose interferon beta-1a) in 825 people with RRMS. In a subset of people in the two active-controlled OPERA clinical studies, patients with at least two relapses within two years prior or one relapse within the prior year and an EDSS score between 0 and 5.5, inclusive, OCREVUS delayed disease progression. OCREVUS demonstrated superior efficacy on the three major markers of disease activity by reducing relapses per year by nearly half, slowing the worsening of disability and significantly reducing MRI lesions compared with the standard of care over the two-year controlled treatment period.14 Data from the study demonstrated the following:

A 46 per cent and 47 per cent 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 < 0.0001 and p < 0.0001).

A 40 per cent relative risk reduction in confirmed disability progression (CDP) sustained for 12 weeks compared with iInterferon beta-1a in a pooled analysis of OPERA I and OPERA II, as measured by the Expanded Disability Status Scale (EDSS) (p=0.0006).

A 94 per cent and 95 per cent relative reduction in the total number of T1 gadolinium-enhancing lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p < 0.0001 and p < 0.0001).

The most frequently reported adverse drug reactions (ADRs) were infusion related reactions (IRRs) and respiratory tract infections.15 In the OPERA clinical studies, symptoms associated with IRRs included, but are not limited to: pruritus, rash, urticaria, erythema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, throat irritation, oropharyngeal pain, dyspnoea, pharyngeal or laryngeal edema, nausea, tachycardia. In the controlled clinical trials there were no fatal IRRs. In the two active-controlled OPERA clinical studies, IRRs were the most common adverse event in patients treated with OCREVUS 600 mg with an overall incidence of 34 per cent compared with an incidence of 10 per cent in the Interferon beta-1a treatment group (placebo infusion). The incidence of IRRs was highest during Dose 1, infusion 1 (27.5 per cent) and decreased over time to <10 per cent at Dose 4. The majority of IRRs in both treatment groups were mild to moderate.16

About OCREVUS

OCREVUS is a humanized monoclonal antibody. Monoclonal antibodies are proteins, which bind to a unique site (called an antigen) on cells. OCREVUS binds to an antigen, called CD20, which is present at high levels on certain cells of your immune system. OCREVUS works on your immune system so that it may not attack your nervous system.

OCREVUS is administered by intravenous infusion every six months. The first dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.17

About Relapsing Remitting Multiple Sclerosis (RRMS)

Multiple Sclerosis is a chronic disease in which the immune system abnormally attacks components of myelin, causing inflammation and consequent damage.18 In patients with MS, damaged nerves lose their ability to communicate with the rest of the body, leading to unpredictable and often debilitating symptoms such as weakness, fatigue, and vision problems.19,20,21 Myelin is a multilayered membrane system, composed primarily of lipids, which surrounds and insulates axons. It is critical for proper electrical,22 trophic,23 and structural24 function of CNS neurons. In MS, the immune system attacks myelin and results in hallmark demyelinating lesions that disrupt communication between the brain and the rest of the body often resulting in disability.25 The cause of MS is undetermined, but current evidence suggests that factors pertaining to lifestyle, genetics, biology and the environment can contribute to the disease.26 There is no evidence to suggest that MS is genetically inherited. While the disease occurs in most ethnic groups, it is most common in people with northern European ancestry.27

Today there are approximately 100,000 Canadians living with MS,28 and RRMS is the most common form. RRMS is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks, known as relapses or exacerbations, are followed by periods of partial or complete recovery (remissions). During a recovery period, all symptoms may disappear, or some symptoms may continue and become permanent.29

About The MindSet & Neurologist Surveys

The Neurologist Survey was a 10-minute online survey conducted by Environics Research, fielded from May 3rd 2017 to June 8th 2017. The survey was completed by 60 Neurologists across Canada, each of which was screened to ensure they had Primary Progressive MS (PPMS) and/or Relapse Remitting (RRMS) patients in their practice. With just over 1,000 Neurologists in Canada, the sample of n=60 yield a margin of error of +/-12.3 per cent at the 95 per cent confidence level.

The Roche MS MindSet Survey was conducted by KRC Research via an online survey with a total of 1,727 people living with MS and 1,751 support partners of someone with MS. The survey was fielded from July 8th to July 25th 2016 in the US; and from January 26th to February 16th 2017 in Canada, France, Germany, Italy, Spain and the UK. There were approximately 250 responses from Canada, giving a margin or error of +/-6.19 per cent at the 95 per cent confidence interval.

About Roche

Headquartered in Basel, Switzerland, Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Roche Canada was founded in 1931. The company employs over 1,000 people across the country, with its pharmaceuticals head office located in Mississauga, Ontario, and diagnostics division based in Laval, Quebec. Roche Canada is actively involved in local communities, investing in charitable organizations and partnering with healthcare institutions across the country. For more information, visit www.rochecanada.com.

About Roche in Neuroscience

Neuroscience is a major focus of research and development at 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.

All trademarks mentioned are the property of their respective owners.

© Copyright 2017; Hoffmann-La Roche Limited

REFERENCES

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1 Ocrevus (ocrelizumab) Product Monograph; August 14, 2017.

2 Ocrevus (ocrelizumab) Product Monograph; August 14, 2017.

3 Ocrevus (ocrelizumab) Product Monograph; August 14, 2017.

4 Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625013/. Last accessed July 25, 2017.

5 Environics Research. Neurologist Survey; 2017

6 Statistics Canada. Neurological conditions, by age group and sex, household population aged 0 and over, 2010/2011.

http://www5.statcan.gc.ca/cansim/a26?lang=eng&retrLang=eng&id=1051300&paSer=&pattern=&stByVal=1&p1=1&p2=31&tabMode=dataTable&csid. Last accessed July 24, 2017.

7 Multiple Sclerosis Society of Canada. MS Types. https://mssociety.ca/about-ms/types

Last accessed July 12, 2017.

8 Compston, A. and Alasdair Coles. Multiple Sclerosis. 2008. Lancet. 372: 1502-17.

9 Subei, A.M. and Eric Eggenberger. Efferent manifestations of multiple sclerosis. Current Opinion in Ophthalmology. 2012. 23(6): 506-509.

10 National Multiple Sclerosis Society. What is Multiple Sclerosis? http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-What-Is-MS.pdf. Last accessed July 24, 2017.

11 KRC Research. MindSet Survey; 2016

12 MindSet Survey (online survey conducted by KRC Research, fielded from July 8th to July 25th 2016. The survey was completed by 1,727 people living with MS and 1,751 support partners of someone with MS in Canada, France, Germany, Italy, Spain and the UK. The 250 responses yield a margin of error of +/-6.19% at the 95% confidence interval.)

13 Ocrevus (ocrelizumab) Product Monograph; August 14, 2017.

14 Ocrevus (ocrelizumab) Product Monograph; August 14, 2017.

15 Ocrevus (ocrelizumab) Product Monograph; August 14, 2017.

16 Ibid

17 Ibid

18 Hartung, H.P. et al. Immune regulation of multiple sclerosis. Handbook of Clinical Neurology. 2014. 122(3):3-14.

19 Compston, A. and Alasdair Coles. Multiple Sclerosis. Lancet. 2008. 372: 1502-17.

20 Subei, A.M. and Eric Eggenberger. Efferent manifestations of multiple sclerosis. Current Opinion in Opthalmology. 2012. 23(6): 506-509.

21 National Multiple Sclerosis Society. What is Multiple Sclerosis?

http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-What-Is-MS.pdf. Last accessed July 24, 2017.

22 Soldan, P. et al. Biogenesis and Significance of Central Nervous System Myelin. Seminars in Neurology. 2012. 32:9-14.

23 Dai X. et al. The Trophic Role of Oligodendrocytes in the Basal Forebrain. The Journal of Neuroscience. 2003. 23(13):5846-5853.

24 Brady S. et al. Formation of Compact Myelin Is Required for Maturation of the Axonal Cytoskeleton. The Journal of Neuroscience. 1999. 19(7):7278-7288.

25 Lucchinetti, C. et al. Distinct Patterns of Multiple Sclerosis Pathology Indicates Heterogeneity in Pathogenesis. Brain Pathology. 1996. 6:259-274.

26 Multiple Sclerosis Society of Canada. What is MS? https://mssociety.ca/about-ms/what-is-ms. Last accessed July 24, 2017.

27 National Multiple Sclerosis Society. Multiple Sclerosis FAQs. http://www.nationalmssociety.org/What-is-MS/MS-FAQ-s. Last accessed July 24, 2017.

28 Statistics Canada. Neurological conditions, by age group and sex, household population aged 0 and over, 2010/2011. http://www5.statcan.gc.ca/cansim/a26?lang=eng&retrLang=eng&id=1051300&paSer=&pattern=&stByVal=1&p1=1&p2=31&tabMode=dataTable&csid. Last accessed July 24, 2017.

29 National Multiple Sclerosis Society. Relapsing-remitting MS (RRMS). http://www.nationalmssociety.org/What-is-MS/Types-of-MS/Relapsing-remitting-MS. Last accessed June 29, 2017.

SOURCE Roche Canada

For further information: Ashley Iyer-Dhillon, Roche Canada, T: 416-561-3286, E: [email protected]; Sheba Zaidi, Environics Communications, T: 416-969-2652, E: [email protected]