Health Canada Approves ACTEMRA® (tocilizumab) for Canadians Living with Giant Cell Arteritis (GCA)

ACTEMRA^® is the first non-steroid treatment designed to directly target the interleukin-6 (IL-6) receptor, offering a new option to treat GCA¹

MISSISSAUGA, ON, Nov. 2, 2017 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) today announced that Health Canada has approved ACTEMRA^® (tocilizumab) for the treatment of adult patients with giant cell arteritis (GCA).²  The approval was based on the outcome of the phase III GiACTA study, which showed that ACTEMRA, initially combined with a six-month steroid taper, sustained remission at one year in 56 per cent and 53 per cent of patients (with the weekly and bi-weekly doses respectively), compared to 14 per cent of patients in the placebo arm with a six-month steroid taper given alone.³

ACTEMRA is designed to directly target the interleukin-6 (IL-6) receptor, a protein that is made by the immune system, which the body uses to manage infections and plays a major role in the signs and symptoms of GCA.⁴ There have been no new treatments in more than 50 years.^5,6

"When GCA is diagnosed too late or left untreated, it can cause serious, even potentially life-threatening, complications," says Dr. Christian Pagnoux, Internal Medicine Specialist and Rheumatologist at Mount Sinai Hospital in Toronto. "Treatment of GCA patients was limited to high-dose, long-duration steroids, and relapses were almost constant. The approval of Actemra provides physicians in Canada with a new treatment option."

GCA is the most common form of vasculitis that occurs in adults. It is caused by inflammation of the lining of the arteries.⁷ The disease often affects the arteries in the head, specifically around the temples and if GCA is left untreated, it can lead to stroke or blindness.⁸ Generally, GCA affects adults older than 50 years of age and is three times more likely to occur in women than in men.⁹ GCA causes headaches, visual impairment, vision loss, claudication (cramping caused by lack of blood flow)¹⁰ of the jaw, arms and legs,¹¹ and can lead to aortic aneurysm, myocardial infarction, and stroke.¹²

About the Health Canada Approval
The approval of ACTEMRA (tocilizumab) for the treatment of adult patients with giant cell arteritis (GCA) was based on the randomized, double-blind, placebo-controlled, phase III GiACTA study. The GiACTA study investigated whether ACTEMRA resulted in higher rates of sustained glucocorticoid-free remission of GCA in comparison to placebo through a period of 52 weeks.¹³

The GiACTA study evaluated the safety and efficacy of ACTEMRA for the treatment of GCA in 251 patients with new-onset or relapsing GCA (cranial GCA and large-vessel vasculitis) who were enrolled and assigned to one of four treatment arms. The study consisted of a 52-week blinded period (Part 1), followed by a 104-week open-label extension (Part 2). Relationships between ACTEMRA concentrations to safety and efficacy endpoints were assessed. The purpose of Part 2 is to describe the long-term safety and maintenance of efficacy after 52 weeks of ACTEMRA therapy, to explore the rate of relapse and the requirement for ACTEMRA therapy beyond 52 weeks, and to gain insight into the potential long-term steroid-sparing effect of ACTEMRA. Two subcutaneous (SC) doses of ACTEMRA (162 mg every week and 162 mg every other week) were compared to two different placebo randomized control groups 2:1:1:1. All patients received background glucocorticoid (prednisone) therapy. Each of the ACTEMRA-treated groups and one of the placebo-treated groups followed a pre-specified prednisone-taper regimen over 26 weeks, while the second placebo-treated group followed a pre-specified prednisone-taper regimen over 52 weeks designed to be more in keeping with standard practice. 

The overall safety profile observed in the ACTEMRA GCA study was, in general, consistent with the known safety profile of ACTEMRA, including upper respiratory tract infections (common cold, sinus infections) headaches, and increase in blood pressure. The most common serious infections included pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis and bacterial arthritis. Opportunistic infections including tuberculosis, cryptococcus, aspergillosis, candidiasis, and pneumocystosis were reported with ACTEMRA.¹⁴

No new safety signals were observed with ACTEMRA in the GiACTA study. There was no difference in safety profile between the arms of the study. ACTEMRA did not add to the safety profile of a six-month steroid taper. The safety of subcutaneous ACTEMRA has been studied in the phase III study GiACTA study in 251 GCA patients. While the overall safety profile observed in the ACTEMRA treatment groups was generally consistent with the known safety profile of ACTEMRA in other indications, there was an overall higher incidence of infections in GCA patients relative to rheumatoid arthritis (RA) patients.¹⁵

About ACTEMRA
ACTEMRA (tocilizumab) is a recombinant humanized anti-human IL-6 receptor monoclonal antibody of the immunoglobulin IgG1κ (gamma 1, kappa) subclass with a typical H2L2 polypeptide structure. ACTEMRA is composed of two heterodimers, and each of the heterodimers is composed of a heavy (H) and a light (L) polypeptide chain. Each light chain and heavy chain consists of 214 and 448 amino acids, respectively. The four polypeptide chains are linked intra- and inter-molecularly by disulfide bonds. ACTEMRA has a molecular weight of approximately 148 kDa.¹⁶

ACTEMRA is administered through subcutaneous (SC) injection and is supplied as a sterile yellowish, preservative-free liquid at a concentration of 162 mg/0.9 mL. Ready-to-use, single-use pre-filled syringes with needle safety device are available.¹⁷

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. 

All trademarks mentioned are the property of their respective owners.

© Copyright 2017; Hoffmann-La Roche Limited

REFERENCES
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¹ Stone, JH. Trial of Tocilizumab in Giant-Cell Arteritis. July 27, 2017. 317.4
² ACTEMRA (tocilizumab) Product Monograph; October 27 2017.
³ Stone, JH. Trial of Tocilizumab in Giant-Cell Arteritis. July 27, 2017. 317.4
⁴ ACTEMRA (tocilizumab) Product Monograph; October 27, 2017.
⁵ Borchers AT, et al. Giant cell arteritis: A review of classification, pathophysiology, geoepidemiology and treatment. Autoimmunity Reviews. 2012; 11:A544-5554.
⁶ Ponte C, et al. Giant cell arteritis: Current treatment and management. World J Clin Cases. 2015; 3(6):484-494.
⁷ The Johns Hopkins Vasculitis Center. Types of Vasculitis: Giant Cell Arteritis. https://www.hopkinsvasculitis.org/types-vasculitis/giant-cell-arteritis/. Last Accessed October 13, 2017
⁸ Mayo Clinic. Diseases & Conditions: Giant Cell Arteritis. 
 http://www.mayoclinic.org/diseases-conditions/giant-cell-arteritis/basics/definition/con-20023109. Last Accessed Oct 3, 2017.
⁹ The Johns Hopkins Vasculitis Center. Types of Vasculitis: Giant Cell Arteritis.
https://www.hopkinsvasculitis.org/types-vasculitis/giant-cell-arteritis/. Last Accessed October 13, 2017
¹⁰ Mayo Clinic. Disease & Condition. Claudication http://www.mayoclinic.org/diseases-conditions/claudication/basics/definition/con-20033581. Last Accessed Oct 3, 2017
¹¹ Mayo Clinic. Disease & Conditions: Polymyalgia Rheumatica
http://www.mayoclinic.org/diseases-conditions/polymyalgia-rheumatica/basics/definition/con-20023162. Last Accessed October 3, 2017
¹² Stone, JH. Trial of Tocilizumab in Giant-Cell Arteritis. July 27, 2017. 317.4
¹³ Ibid
¹⁴ ACTEMRA Product Monograph. October 27, 2017
¹⁵ ACTEMRA Product Monograph. October 27, 2017
¹⁶ Ibid
¹⁷ Ibid

SOURCE Roche Canada