FDA Approves New Subcutaneous Formulation of Actemra
Genentech Gains FDA Approval for New Subcutaneous Formulation of Actemra for use in Adult Patients Living with Moderately to Severely Active Rheumatoid Arthritis
South San Francisco, Calif., October 21, 2013 -- Genentech, a member of the Roche Group, today announced that the U.S. Food and Drug Administration (FDA) has approved a subcutaneous (SC) formulation of Actemra (tocilizumab) for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have used one or more disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), that did not provide enough relief. Like the intravenous (IV) formulation, the SC formulation can be used both as a single-agent therapy and in combination with MTX or other non-biologic DMARDs. The Actemra pre-filled syringe (PFS) injection formulation will be available in November.
“People with moderately to severely active rheumatoid arthritis can suffer irreversible joint damage that may be prevented by earlier treatment with a medicine such as Actemra," said Hal Barron, M.D., chief medical officer and head, Global Product Development. "We're pleased that these patients will now have the option of Actemra as a subcutaneous injection or an IV infusion."
Actemra, originally approved by the FDA as an IV medicine in 2010, is the first and only humanized interleukin-6 (IL-6) receptor-antagonist monoclonal antibody approved by the FDA for both SC and IV administration.
“Because some patients prefer a subcutaneous injection, it is important for physicians to have this new option,” said Alan J. Kivitz, M.D., FACR, President of Altoona Center for Clinical Research, Duncansville, Pa.1 “In clinical trials, Actemra was shown to be effective and have a consistent safety profile – with the exception of injection site reactions for the subcutaneous formulation – when administered either intravenously or subcutaneously and may be used with or without methotrexate.”
The approval is based on data from the Phase III clinical trials SUMMACTA and BREVACTA. For Actemra SC, the FDA recommended dosage is 162 mg administered subcutaneously every other week, followed by an increase to 162 mg every week based on clinical response for patients less than 100 kg (220 lbs) in weight. For patients at or above 100 kg (220 lbs), the dosing is 162 mg administered subcutaneously every week.
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.
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.
ACR20 score represents a 20 percent 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
Health Assessment Questionnaire (HAQ)
About Rheumatoid Arthritis
RA is an autoimmune disease estimated to affect approximately 1.3 million adults in the United States.2 Joints become chronically inflamed, painful and swollen, and patients can become increasingly disabled as cartilage and bone is damaged.
About Actemra® (tocilizumab)
Actemra is the first humanized interleukin-6 (IL-6) receptor antagonist approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have used one or more disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), that did not provide enough relief. The extensive Actemra RA IV clinical development program included five Phase III clinical studies and enrolled more than 4,000 people with RA in 41 countries, including the United States. The Actemra RA SC clinical development program included two Phase III clinical studies and enrolled more than 1,800 people with RA in 33 countries, including the United States. In addition, Actemra is also used as an IV formulation for patients with active polyarticular juvenile idiopathic arthritis (PJIA) or systemic juvenile idiopathic arthritis (SJIA) two years of age and older.
Actemra is intended for use under the guidance of a healthcare practitioner.
Important Safety Information
Actemra can cause serious side effects. Actemra changes the way a patient’s immune system works. This can make a patient more likely to get infections or make any current infection worse. Some people taking Actemra have died from these infections.
Actemra can cause other serious side effects. These include:
changes in blood test results, including low neutrophil (white blood cells) and platelet (platelets help the blood to clot) counts, and increases in certain liver function test levels and blood cholesterol levels
an increased risk of certain cancers by changing the way a patient’s immune system works
hepatitis B infection
serious allergic reactions, including death. These may happen with Actemra infusions or injections, even if they did not occur with an earlier infusion or injection.
nervous system problems
Patients must tell their doctor if they are allergic to Actemra or if they have had a bad reaction to Actemra previously.
Common side effects:
Patients must tell their doctor if they have these or any other side effect that bothers them or does not go away:
Upper respiratory tract infections (like common cold and sinus infections)
Increased blood pressure (also called hypertension)
Injection site reactions
Actemra & pregnancy:
Patients must tell their doctor if they are planning to become pregnant, are pregnant, plan to breast-feed, or are breast-feeding. The patient and their doctor should decide if the patient will take Actemra or breast-feed. Patients should not do both. If a patient is pregnant and taking Actemra, they must join the pregnancy registry. To learn more, patients should call 1-877-311-8972 or talk to their doctor to register.
Patients must tell their doctor right away if they are experiencing any side effects. Report side effects to the FDA at 1-800-FDA-1088 or www.FDA.gov/medwatch. Call Genentech at 1-888-835-2555.
Please visit www.actemra.com for the full Prescribing Information, including Boxed Warning and Medication Guide, for additional Important Safety Information or call 1-800-ACTEMRA (228-3672).
Actemra is part of a co-development agreement with Chugai Pharmaceutical Co. and has been approved in Japan since June 2005. Actemra is approved in the European Union, where it is known as RoActemra, and several other countries, including China, India, Brazil, Switzerland and Australia.
About Genentech Access Solutions
Genentech is committed to people having access to its medicines. Genentech Access Solutions is a team of more than 350 Genentech employees who help those who need medications. Knowledgeable and experienced specialists can help patients and medical practices navigate the access and reimbursement process and provide assistance to eligible patients in the United States who do not have insurance coverage or who cannot afford their out-of-pocket co-pay costs. For more information, please visithttp://www.GenentechAccessSolutions.com.
Founded more than 35 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, Calif. For additional information about the company, please visit http://www.gene.com.
1. Barton, Jennifer. Patient Preferences and Satisfaction in the Treatment of Rheumatoid Arthritis with Biologic Therapy. Patient Preference and Adherence. 2009; 3: 335-344. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792871/. Accessed July 19, 2013.
2. Arthritis Foundation. Available at: http://www.arthritis.org. Accessed July 22, 2013.
Posted: October 2013
- FDA Approves Actemra for Children with Polyarticular Juvenile Idiopathic Arthritis - April 30, 2013
- FDA Approves Actemra (tocilizumab) for the Treatment of Systemic Juvenile Idiopathic Arthritis (SJIA) - April 17, 2011
- FDA Grants Supplemental Approval for Actemra (tocilizumab) - January 5, 2011
- FDA Approves Actemra for the Treatment of Moderately to Severely Active Rheumatoid Arthritis - January 11, 2010
- Roche and FDA Agree on Pathway Towards U.S. Approval of Actemra (tocilizumab) - December 4, 2008
- FDA Issues Complete Response Letter to Roche for Acterma (tocilizumab) Biologics License Application - September 18, 2008
- FDA Advisory Committee Recommends Approval of Actemra (tocilizumab) for the Treatment of Rheumatoid Arthritis - July 29, 2008
- Roche Submits Application for FDA Approval of Actemra for the Treatment of Rheumatoid Arthritis - November 21, 2007