FDA Approves Actemra

FDA Approves Actemra for the Treatment of Moderately to Severely Active Rheumatoid Arthritis

BASEL, Switzerland, Jan. 11, 2010 - Roche today announced that the United States (US) Food and Drug Administration (FDA) approved Actemra (tocilizumab, RoActemra in the European Union) for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Actemra, the result of a research & development collaboration with Chugai, is the first interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody approved to treat RA, may be used alone or in combination with methotrexate or other disease modifying anti-rheumatic drugs (DMARDs).

"The FDA approval of Actemra marks a major step forward in the treatment of RA, providing a new option for patients with this very serious disease," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Roche and Genentech. "We are optimistic that working with the agency, we will be able to generate the additional data required to support approval in earlier lines of RA therapy and are committed to comprehensively characterizing both the clinical benefit and the safety of Actemra in earlier lines of therapy through our large pharmacovigilance program, including the risk management program, and ongoing clinical and post-marketing studies globally."

RA is a chronic, progressive inflammatory disease of the joints and surrounding tissues that is associated with intense pain, irreversible joint destruction and systemic complications. There are several key cytokines, or proteins, involved in the inflammatory process, including IL-6. Research shows that IL-6 levels are elevated in patients with RA. Actemra is the first medication designed to specifically inhibit the biological activity of IL-6.

"For many RA patients, treatment with existing therapies does not resolve the painful and debilitating symptoms of the disease," said Mark Genovese, M.D., Actemra study investigator and Professor of Medicine and Co-Chief of the Division of Immunology and Rheumatology at Stanford University Medical Center. "Data from the clinical development program clearly establish Actemra and its unique mechanism of action as an important new option for RA patients who experience continued disease symptoms despite treatment with existing therapies."

Actemra has been studied in five multi-national Phase III studies, involving more than 4,000 patients, making it the largest clinical development program for an indication in RA to date. The studies showed that Actemra – alone or in combination with methotrexate or other DMARDs – significantly reduced RA signs and symptoms, regardless of previous therapy, compared with DMARDs alone.

Actemra will be available in the US the week of January 18 2010.

The treatment is also approved for use in the European Union and a growing number of other countries including Mexico, India, Brazil, Switzerland and Australia

This approval is based on data from the following pivotal studies:
RADIATE (RheumAtoiD ArthritIs Study in Anti-TNF FailurEs) Trial:
• 50% and 30% of patients who received Actemra 8 mg/kg or 4 mg/kg plus methotrexate, respectively, achieved ACR20 at week 24, compared with 10% of patients who received placebo plus methotrexatei
OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders) Trial:
• 59% and 48% of patients who received Actemra 8 mg/kg and 4 mg/kg plus methotrexate, respectively, achieved ACR20 at week 24, compared with 27% of patients who received placebo plus methotrexateii
TOWARD (Tocilizumab in cOmbination With traditional DMARD therapy) Trial:
• 61% of patients who received Actemra 8mg/kg plus DMARD(s) achieved ACR20 at 24 weeks, compared with 25% of patients treated with DMARDs plus placeboiii
AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) Trial:
• 70% of patients who received Actemra 8 mg/kg achieved ACR20 at week 24, compared with 53% of patients receiving methotrexate aloneiv
LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage) Trial:
• 56% and 51% of patients who received Actemra 8 mg/kg or 4 mg/kg plus methotrexate, respectively, achieved ACR20 at Week 24 compared with 27% of patients who received placebo plus methotrexat

About Actemra

Actemra is the first humanised IL-6 receptor-inhibiting monoclonal antibody. An extensive clinical development programme of five Phase III trials was designed to evaluate clinical findings of Actemra, all of which met their primary endpoints. Actemra was first approved in Japan, and launched by Chugai in June 2005 as a therapy for Castleman's disease; in April 2008, additional indications for RA, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan. Actemra was approved in the European Union in January 2009 for the treatment of RA in patients who have either responded inadequately to, or who were intolerant to, previous therapy with one or more DMARDs or TNF inhibitors. It is also approved for use in several other countries, including Mexico, India, Brazil, Switzerland and Australia.

The overall safety profile of Actemra is consistent across all global clinical studies.
Serious side effects associated with Actemra include serious infections that may lead to hospitalization or death, gastrointestinal perforations (a hole in the stomach or intestines), and hypersensitivity reactions including anaphylaxis. The most common AEs reported in clinical studies were upper respiratory tract infection, nasopharyngitis (inflammation of the nose and throat), headache, high blood pressure and increased liver enzymes. The increases in liver enzymes that were seen in patients were generally mild and reversible and did not result in apparent permanent or clinically evident hepatic injury. Laboratory changes, including increases in total cholesterol, the amount of fat circulating in the blood, and decreases in neutrophils (one of the cell types that helps fight infections) and platelets, were seen. Treatments that suppress the immune system, such as Actemra, may cause an increase in the risk of cancer.

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, virology, inflammation, metabolism and central nervous system (CNS).

Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2008, Roche had over 80,000 employees worldwide and invested almost 9 billion Swiss francs in R&D. The Roche Group posted sales of 45.6 billion Swiss francs. Genentech, United States, is a wholly owned member of the Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

Further information
- Roche & Autoimmune diseases:
http://www.roche.com/about_roche/business_fields/disease_areas/inflammation.htm
- Chugai: www.chugai-pharm.co.jp
Roche Group Media Relations
Phone: +41 -61 688 8888 / e-mail: basel.mediaoffice@roche.com
- Alexander Klauser
- Martina Rupp
- Claudia Schmitt
- Nina Schwab-Hautzinger
i Emery P. et al. IL-6 Receptor Inhibition with Tocilizumab Improves Treatment Outcomes in Patients with Rheumatoid Arthritis
Refractory to Anti-TNF Biologics: The RADIATE Study. Annals of the Rheumatic Diseases. 2008;67:1516-1523.
ii Smolen J. et al. Effect of Interleukin-6 Receptor Inhibition with Tocilizumab in Patients with Rheumatoid Arthritis (OPTION
Study): a Double-Blind, Placebo-Controlled, Randomised Trial. The Lancet. 2008;371,9617:987-997.
iii Genovese M., et al. Interleukin-6 Receptor Inhibition with Tocilizumab Reduces Disease Activity in Rheumatoid Arthritis with
Inadequate Response to Disease-Modifying Antirheumatic Drugs. Arthritis & Rheumatism. 2008;58(10):2968-2980.
iv Jones. G. Abstract 1210. The AMBITION Study: Superiority of Tociluzumab (TCZ) vs Methotrexate (MTX) Monotherapy in
Patients with Rheumatoid Arthritis (RA). Data presented at the American College of Rheumatology (ACR) Annual Scientific Meeting
2008.
v Fleischmann R., Abstract 637. LITHE: Tocilizumab Inhibits Radiographic Progression and Improves Physical Function in
Rheumatoid Arthritis (RA) Patients (Pts) at 2 Yrs with Increasing Clinical Efficacy Over Time. Data presented at ACR 2008.

Posted: January 2010

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Actemra (tocilizumab) FDA Approval History

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