Health Canada Approves OCREVUS® (ocrelizumab) for Canadians Living with Primary Progressive Multiple Sclerosis (PPMS)

OCREVUS is a new treatment for a rare and worsening form of MS that impacts
10-15 per cent of Canadians living with the disease¹

MISSISSAUGA, ON, Feb. 15, 2018 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) today announced that Health Canada has approved OCREVUS^® (ocrelizumab), with conditions, as a monotherapy for the management of adult patients with early primary progressive multiple sclerosis (PPMS) as defined by disease duration and level of disability, in conjunction with imaging features characteristic of inflammatory activity. Disability is commonly determined by using the Expanded Disability Status Scale (EDSS) to quantify physical deterioration in multiple sclerosis (MS) and to monitor changes in the level of impairment over time.  Scoring is based on the examination of a patient by a neurologist.²  

Health Canada has approved OCREVUS under provisions made within its Notice of Compliance with Conditions (NOC/c) policy. This policy facilitates earlier access to promising new medicines that treat, prevent or diagnose serious, life-threatening and/or severely debilitating diseases for which there is no alternative medicine available in Canada, or where the new medicine offers an overall benefit/risk profile which shows improvement over existing therapies.³

"This is exciting news for the MS community," says Dr. Karen Lee, Vice-President of Research at the Multiple Sclerosis Society of Canada. "Over the years we have seen many new treatments come to market that manage relapsing-remitting MS (RRMS) but there have been no disease modifying therapies for people living with progressive MS.  The approval of Ocrevus is a much-needed treatment for the PPMS community because, for some people living with PPMS, Ocrevus may help control, and even slow disease progression. Hopefully, this is the beginning of many more treatment options for people living with PPMS."

Roughly 100,000 Canadians are living with MS⁴ – one of the highest prevalence rates in the world – often referred to as "Canada's disease." About one in 10 of these Canadians is battling PPMS, a debilitating form of the disease, which results in difficulty walking – a sign of spinal cord disease, as well as brain and spinal cord atrophy (or shrinkage).⁵  Unlike other forms of MS such as RRMS, where patients may have periods of remission between attacks, PPMS is a deteriorating form of the disease, characterized by steadily worsening neurological function without periods of relapse and remission.⁶

"Being diagnosed with PPMS and learning that there were no treatment options for my type of MS left me feeling hopeless," says Mike Schofield, patient living with multiple sclerosis. "So when my doctor spoke to me about participating in a clinical trial for an experimental medicine, I felt like I had nothing to lose.  I'm living proof that research pays off and I'm proud to have been part of the process that has made it possible for other patients to now access Ocrevus."

OCREVUS offers the medical community a wholly new pathway to treating MS, as it is the first approved recombinant humanized antibody that selectively targets B cells that express the CD20 antigen (a protein found on the surface of B cells).⁷ Prior to the discovery of OCREVUS, MS was thought to be a T cell (white blood cell developed by the thymus gland) driven disease.⁸

"The management of progressive MS has long been very frustrating for both patients and clinicians because we have been limited to symptom management," says Dr. Daniel Selchen, a neurologist at St. Michael's Hospital. "The approval of Ocrevus for patients with PPMS affords the opportunity to, for the first time, offer a disease modifying therapy (DMT) to patients with progressive disease. This will benefit some patients both clinically, by delaying disease progression, and psychologically, by offering hope. It will be important for clinicians to help manage patient expectations, as not all patients who receive treatment with Ocrevus will benefit and many PPMS patients will not be appropriate candidates for this therapy."

About the ORATORIO Study & OCREVUS

ORATORIO is a randomised, double-blind, global multi-centre study evaluating the efficacy and safety of ocrelizumab (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 PPMS. The blinded treatment period of the ORATORIO study continued until all patients had received at least 120 weeks of either ocrelizumab or placebo, and a predefined number of confirmed disability progression (CDP) events was reached overall in the study. Data from the study demonstrated the following:⁹

• A 24 per cent relative risk reduction in CDP sustained for at least 12 weeks compared with placebo, as measured by the EDSS (p=0.03).
• A 25 per cent relative risk reduction in CDP sustained for at least 24 weeks compared with placebo (p=0.04).
• A 3.4 per cent reduction in the total volume of brain hyperintense T2 lesions compared with a 7.4 per cent increase in placebo-treated patients over 120 weeks (p<0.001).

The safety of OCREVUS has been evaluated in 486 patients, in the placebo controlled ORATORIO (PPMS) study. The most common (incidence≥10 per cent) adverse drug reactions (ADRs) were infusion related reactions (IRRs [40 per cent vs. 26 per cent]), upper respiratory tract infections (12 per cent vs. 6 per cent) and influenza (12 per cent vs. 8 per cent).¹⁰ Patients were given OCREVUS 600 mg (n=486) or placebo (n=239) every 6 months (administered as two 300 mg infusions separated by 2 weeks during the entire study). In the ORATORIO study, symptoms associated with infusion related reactions (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. The incidence of IRRs was highest during Dose 1, infusion 1 (27.4 per cent) and decreased with subsequent doses to <10 per cent at Dose 4.  A greater proportion of patients in each group experienced IRRs with the first infusion of each dose compared with the second infusion of that dose.  The majority of IRRs were mild to moderate.¹¹

There was no increase in serious infections associated with OCREVUS treatment (the rate of serious infections was similar to placebo). The respiratory tract infections and herpes infections (both predominantly mild to moderate) were more frequently reported in the OCREVUS treatment arm. The proportion of respiratory tract infections was higher in the OCREVUS treated patients compared to placebo.  The infections were predominately mild to moderate and consisted mostly of upper respiratory tract infections (including nasopharyngitis) and bronchitis. There were higher proportions of patients with oral herpes (2.7 per cent vs 0.8 per cent) observed in the OCREVUS treatment arm.¹²

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 B 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 infusion.¹³

About Primary Progressive Multiple Sclerosis

MS is an autoimmune disease affecting the central nervous system, which is primarily made up of the brain and spinal cord. It attacks the nerves' protective covering (myelin), often damaging it and causing inflammation. Without myelin, nerve impulses cannot to be transmitted through nerve fibres.¹⁴  PPMS is a debilitating form of MS, which results in difficulty walking – a sign of spinal cord disease, as well as brain and spinal cord atrophy (or shrinkage).¹⁵ Unlike other forms of MS such as RRMS, where the patients may have periods of remission between attacks, PPMS is a deteriorating form of the disease, characterized by steadily worsening neurological function without periods of relapse and remission.¹⁶

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 trade-marks mentioned are the property of their respective owners.

© Copyright 2018; Hoffmann-La Roche Limited

REFERENCES
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^1	Kyla A. Mckay, et al. Risk Factors Associated with the Onset of Relapsing-Remitting and Primary Progressive Multiple Sclerosis: A Systematic Review. Biomed Research International. 2014. https://www.hindawi.com/journals/bmri/2015/817238/. Last accessed Nov 13, 2017.
^2	Multiple Sclerosis Trust. Expanded Disability Status Scale (EDSS). Questions. 2017. https://www.mstrust.org.uk/a-z/expanded-disability-status-scale-edss. Last accessed November 13, 2017.
^3	Health Canada's Notice of Compliance with Conditions policy (NOC/c) https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/notice-compliance-conditions.html#a2. Last accessed Jan 10, 2017.
^4	Statistics Canada. Neurological conditions, by age group and sex, household population aged 0 and over,2010/2011. Government of Canada. 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 Nov 13, 2017.
^5	Multiple Sclerosis Society of Canada. Managing Multiple Sclerosis. https://mssociety.ca/managing-ms/living-with-ms/progressive-ms. Last accessed Nov 13, 2017.
^6	Kyla A. Mckay, et al. Risk Factors Associated with the Onset of Relapsing-Remitting and Primary Progressive Multiple Sclerosis: A Systematic Review. Biomed Research International. 2014. https://www.hindawi.com/journals/bmri/2015/817238/. Last accessed Nov 13, 2017.
^7	OCREVUS^® (ocrelizumab) Product Monograph. February 2018.
^8	G. Disanto et al. The evidence for a role of B cells in multiple sclerosis. The Official Journal of the American Academy of Neurology. 2012.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304944/. Last accessed November 13, 2017.
^9	OCREVUS^® (ocrelizumab) Product Monograph. February 2018.
^10	OCREVUS^® (ocrelizumab) Product Monograph. February 2018.
^11	Ibid.
^12	Ibid.
^13	Ibid.
^14	Multiple Sclerosis Society of Canada. What is MS? https://mssociety.ca/about-ms/what-is-ms. Last accessed November 13, 2017.
^15	Multiple Sclerosis Society of Canada. Managing Multiple Sclerosis. https://mssociety.ca/managing-ms/living-with-ms/progressive-ms. Last accessed Nov 13, 2017.
^16	Multiple Sclerosis Society of Canada. Managing Multiple Sclerosis.https://mssociety.ca/managing-ms/living-with-ms/progressive-ms. Last accessed Nov 13, 2017.

SOURCE Roche Canada

Ashley Iyer-Dhillon, Roche Canada, T: 905-542-5907, E: [email protected]; Harry Godfrey, Environics Communications, T: 416-969-1657, E: [email protected]