Health Canada Approves ACTEMRA® (tocilizumab) Subcutaneous For Use In Adult Patients Living With Moderately To Severely Active Rheumatoid Arthritis

MISSISSAUGA, ON, May 8, 2014 /CNW/ - Roche today announced that Health Canada has approved a subcutaneous (SC) formulation of ACTEMRA (tocilizumab) for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have inadequate response to one or more disease modifying anti-rheumatic drugs (DMARDs) and/or tumour necrosis factor (TNF) antagonists.¹ Like the intravenous (IV) formulation, the SC formulation can be used both as a single-agent therapy, or monotherapy, and in combination with methotrexate or other non-biologic DMARDs.² The ACTEMRA pre-filled syringe (PFS) injection formulation will be available in Canada in June.

ACTEMRA SC is the first and only humanized interleukin-6 receptor-antagonist monoclonal antibody approved by Health Canada for both subcutaneous and intravenous administration in rheumatoid arthritis. The subcutaneous formulation has comparable efficacy and safety to the IV formulation.^3,4 Under guidance of a healthcare practitioner and after appropriate training, adult patients or the patient's caregiver will be able to administer ACTEMRA SC via a pre-filled syringe at home.¹

"ACTEMRA SC is an option for RA patients who are better suited to a subcutaneous injection or for those who don't respond well to methotrexate, as it can be administered as a monotherapy," says Dr. Boulos Haraoui, Rheumatologist at Centre hospitalier de l'Université de Montréal (CHUM Montreal). "In the studies, patients responded well to ACTEMRA SC – it reduced inflammation while having a good safety profile."

"This announcement is exciting for RA patients throughout Canada," says Terri Lupton, Registered Nurse Clinician specializing in Rheumatology. "Patients who are currently prescribed a subcutaneous formulation appreciate the ease of self-injection at home, and ACTEMRA SC provides another great option for these patients."

The approval is based on data from the Phase III clinical trials SUMMACTA and BREVACTA. The recommended starting dose of ACTEMRA SC for adult patients who have had an inadequate response to one or more DMARDs and/or TNF antagonists is 162 mg given every other week followed by an increase to once every week based on clinical response as a subcutaneous injection.¹

About SUMMACTA
SUMMACTA is a randomized, double-blind, active-controlled, parallel-group, multicenter study with a double-blind period of 24 weeks in 1,262 patients with moderately to severely active RA. SUMMACTA demonstrated comparable efficacy (non-inferiority) of the SC formulation of ACTEMRA 162 mg given weekly plus DMARDs compared to 8 mg/kg of ACTEMRA given intravenously every four weeks plus DMARDs in patients with moderately to severely active RA in the DMARD-IR population (20 percent of whom had inadequate response to anti-tumor necrosis factor [anti-TNF] therapy). A similar proportion of RA patients in each group experienced at least a 20 percent improvement in tender and swollen joints (American College of Rheumatology [ACR] 20 response) at Week 24 (69 percent with ACTEMRA SC formulation vs. 73 percent with ACTEMRA IV). Analysis of safety at Week 24 showed that the adverse event profile of the SC and IV groups were comparable, except for SC injection site reactions.

About BREVACTA
BREVACTA is a randomized, double-blind, parallel-group study of ACTEMRA SC versus placebo SC in combination with traditional DMARDs in patients with moderately to severely active RA who had an inadequate response to DMARD therapy. In the study, 656 patients were randomly assigned in a 2:1 ratio to two treatment groups receiving ACTEMRA SC every two weeks administered with a PFS and placebo SC every two weeks with a PFS. All patients continued their background DMARD therapy.

Results from BREVACTA showed RA patients who received the SC formulation of ACTEMRA every two weeks plus DMARDs were significantly more likely to have achieved ACR20 response than those given placebo SC plus DMARDs at 24 weeks (61 percent vs. 32 percent, respectively). At Week 24, significantly less structural joint damage progression was observed in patients receiving ACTEMRA SC plus DMARDs compared to placebo plus DMARDs as assessed radiographically and expressed as a change from baseline in the van der Heijde modified total Sharp score (mTSS) (mean change from baseline in mTSS of 0.62 vs. 1.23, respectively, with an adjusted mean difference of -0.60 [-1.1, -0.1]). No new clinically meaningful safety signals for ACTEMRA, except SC injection site reactions, were observed in this study.

About ACR20
ACR20 score represents a 20 per cent reduction in tender and swollen joint counts in addition to a corresponding improvement in three of the following five parameters:

• Acute phase reactant (such as erythrocyte sedimentation rate)
• Patients Global Assessment of Disease Activity
• Physicians Global Assessment of Disease Activity
• Pain scale
• Health Assessment Questionnaire (HAQ)

About Rheumatoid Arthritis (RA)
RA is thought to affect about one per cent of the population worldwide⁵, and has both an emotional and physical impact on a person's quality of life. Physically, RA causes individuals to experience morning stiffness, lack of flexibility, tiredness, pain, and joint swelling, while emotionally, it leaves a large number of patients feeling isolated and alone. In Canada, RA affects about 300,000 individuals, or one in every 100.⁶

RA is a progressive autoimmune disease characterized by inflammation of the membrane lining in the joints throughout the body. This inflammation causes distortion of the joint and impaired function accompanied by pain, stiffness and swelling, ultimately leading to irreversible joint destruction and disability. In addition, the systemic symptoms of RA include fatigue, anemia, and osteoporosis, and may contribute to shortening life expectancy by affecting major organ systems. Furthermore, musculoskeletal conditions, including arthritis, are the second most costly category of diseases in Canada at $16.4 billion.⁷

About ACTEMRA Subcutaneous
ACTEMRA (tocilizumab) subcutaneous is a formulation of ACTEMRA designed to be administered via injection under the skin. It complements the intravenous (IV) formulation that is infused into a vein over a one-hour period in a hospital setting. The subcutaneous formulation of ACTEMRA, along with the IV formulation, allows physicians more flexibility to tailor the treatment to different RA patient's needs.

The ACTEMRA subcutaneous formulation comes in a pre-filled syringe and has comparable efficacy and safety to the established IV formulation.^2,8 Subcutaneous administration via the pre-filled syringe takes approximately 15 seconds. Under the guidance of a healthcare practitioner and after appropriate training, adult patients or the patient's caregiver will be able to administer ACTEMRA via pre-filled syringe at home.¹

About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche's personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-four medicines developed by Roche are included in the World Health Organisation Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2013 the Roche Group employed over 85,000 people worldwide, invested 8.7 billion Swiss francs in R&D and posted sales of 46.8 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

All trademarks used or mentioned are legally protected.

¹ ACTEMRA Product Monograph. Updated May 6, 2014.
² Ogata A et al. A Phase 3 Study of the Efficacy and Safety of Subcutaneous Versus IntravenousTocilizumab Monotherapy in Patients With Rheumatoid Arthritis (MUSASHI). Pages 22,23. August 5, 2013.
³ Burmester G et al. A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe rheumatoid arthritis (SUMMACTA study). Ann Rheum Dis 2013; 0:1–6. doi:10.1136/annrheumdis-2013-203523.
⁴ Kivitz A et al.  A Randomized, Double-Blind, Parallel-Group Study of the Safety and Efficacy of Tocilizumab Subcutaneous Versus Placebo in Combination With Traditional DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis (BREVACTA).  ACR, November 2012.
⁵ Johns Hopkins Arthritis Center. Rheumatoid Arthritis Signs and Symptoms. Retrieved April 3 from http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-symptoms/
⁶ The Arthritis Society. Rheumatoid Arthritis. Retrieved April 3 from http://www.arthritis.ca/document.doc?id=336
⁷ Statistics Canada. Arthritis in Canada. Retrieved April 3 from http://www.acreu.ca/pdf/Arthritis_in_Canada.pdf
⁸ Burmester GR et al. The Efficacy and Safety of Tocilizumab Subcutaneous Versus Tocilizumab Intravenous, in Combination With Traditional DMARDs in Patients With RA at 49 Weeks (SUMMACTA), ACR, October 2013

SOURCE: Roche Canada

Lee Rammage, Roche Canada, 905-542-6047, [email protected]