Sunday, Nov 7, 2010
South San Francisco, Calif. -- November 7, 2010 --Genentech, Inc., a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced updated data from a Phase III study (ROSE) that showed rheumatoid arthritis (RA) patients receiving ACTEMRA® (tocilizumab) experienced a rapid, measured response as early as one week after beginning ACTEMRA, and improvement in disease activity within four weeks. Additionally, combined data from three other Phase III studies showed that RA patients who received ACTEMRA had sustained improvements in signs and symptoms over nearly two years. These data will be presented at the 2010 American College of Rheumatology (ACR) Annual Scientific Meeting in Atlanta, November 7-11, 2010.
Across the pooled studies, the overall safety of ACTEMRA was consistent with earlier data and showed stable rates of serious infections, malignancies, and cardiovascular events with continued exposure.
"Data presented at ACR provide further evidence of the long-term benefits of Actemra in reducing the signs and symptoms in patients with moderate to severe RA," said Hal Barron, M.D., executive vice president, Product Development and chief medical officer. "Also, we are very excited about the new data that showed that Actemra helped children who were suffering from sJIA, the most severe form of juvenile arthritis."
Data from the Phase III TENDER study showed 85 percent (64/75) of children with systemic Juvenile Idiopathic Arthritis (sJIA) receiving ACTEMRA experienced a 30 percent improvement (JIA ACR30) in the signs and symptoms of sJIA and an absence of fever after three months of therapy, compared with 24 percent (9/37) of children receiving placebo (p<0.0001). The TENDER study served as the basis for a supplemental Biologics License Application (sBLA) recently submitted to the U.S. Food and Drug Administration (FDA).
sJIA has the worst long-term prognosis of all childhood arthritis subtypes, accounting for almost two-thirds of all deaths among children with arthritis.1
About the ROSE Study (Abstract # 1808)
The Rapid Onset and Systemic Efficacy (ROSE) study was designed to assess the efficacy of ACTEMRA versus placebo in combination with disease-modifying anti-rheumatic drugs (DMARDs) in reducing signs and symptoms during 24 weeks of treatment in patients with moderate to severe RA who had inadequate clinical response to DMARDs. The primary end point was reached if patients had a 50 percent reduction in signs and symptoms of disease activity (ACR50) at 24 weeks. Efficacy parameters were assessed every four weeks through week 24. Disease activity was also assessed at one week for a subset of 62 patients. Safety and laboratory parameters were assessed throughout the study.
The study showed RA patients receiving ACTEMRA experienced a rapid response as early as one week after beginning treatment as measured by a disease activity score using 28 joint counts (DAS28), and improvement in disease activity within four weeks. Mean DAS28 score showed a greater improvement in the ACTEMRA group (6.53 at baseline to 3.24 at week 24) compared with patients taking placebo (6.55 at baseline and 5.18 at week 24). Improvement in DAS28 was significantly greater in the ACTEMRA group at all time points (p<0.0001). At week four, 34 percent, 13 percent and 4 percent of people who received ACTEMRA had an ACR20, ACR50 and ACR70, respectively.
Safety findings were consistent with the safety profile of ACTEMRA in the Phase III clinical trial program. Serious infections were reported in 2.9 percent (12/409) of patients in the ACTEMRA group versus 0.5 percent (1/205) of patients in the control group. Abnormal tissue growth (neoplasm) was reported in 1.0 percent (4/409) of patients in the ACTEMRA group and in 1.5 percent (3/205) of patients in the control group. Three patients in the ACTEMRA group died. Causes of death were coronary artery arteriosclerosis, sepsis, and hemorrhagic stroke. The deaths due to sepsis and hemorrhagic stroke were considered by the investigator to be possibly related to study medication; the death due to coronary artery arteriosclerosis was considered unrelated to study treatment.
About the Long-Term Efficacy Data (Abstract # 1820)
Pooled data from three Phase III long-term extension studies - LITHE open-label and GROWTH95 and GROWTH96 - showed that ACTEMRA demonstrated sustained clinical improvement over nearly two years and the number of RA patients who achieved ACR50/70, and had low disease activity (LDA) (defined by DAS28 ≤3.2) increased. At 96 weeks, 53 percent of patients had ACR50, 31 percent had ACR70, 65 percent had LDA and 50 percent achieved DAS28 ≤2.6. In some patients, these benefits were maintained for as long as 3.7 years (66 percent of patients achieved ACR50, 45 percent achieve ACR70, 73 percent achieved LDA and 61 percent achieved DAS28 ≤2.6). While proportions that achieved ACR50/70, LDA, and DAS28 remission were maintained to weeks 168 and 192, data must be interpreted with caution due to lower absolute numbers reaching these visits in the extensions. By week 144, 20.0 percent (396/1980) of assessed DMARD-IR patients and 26.9 percent (105/390) of patients who were never exposed or never failed on methotrexate had achieved the major clinical response of ACR70 for 24 consecutive weeks. Patients in this analysis had either previously failed DMARDs or never received or never failed methotrexate therapy, and subsequently received ACTEMRA either as part of their current DMARD regimen or as monotherapy.
Serious side effects with ACTEMRA include infections, including tuberculosis, that can lead to hospitalization and death; tears (perforation) of the stomach and intestines; changes in blood test results, hepatitis B infection in those already carrying the virus, nervous system problems, and serious allergic reactions.
About the TENDER Study (Abstract # 1434)
Additional results from the TENDER study, a randomized, double-blind, Phase III study in 112 patients showed significantly more children who received ACTEMRA had improvements in sJIA signs and symptoms (JIA ACR30 - 85 percent vs. 11 percent on placebo; JIA ACR70 - 71 percent vs. 8 percent on placebo; JIA ACR90 - 37 percent vs. 5 percent on placebo; p<0.0001). Serious adverse events (SAEs) were observed in three patients (4 percent) receiving ACTEMRA. These SAEs included angioedema (swelling beneath the skin) and urticaria (hives) in one patient and varicella (chickenpox) and bacterial arthritis.
About Systemic Juvenile Idiopathic Arthritis (sJIA)
sJIA is characterized by chronic arthritis accompanied by fever, skin rash, anemia, enlargement of the liver and/or spleen and inflammation of the lining of the heart and/or lungs.2 Peak age of onset of sJIA is between 18 months and two years3,4 although persistence of the disease into adulthood does occur. The disease course is variable and in the most severe cases, up to two-thirds of patients have chronic and persistent arthritis and approximately half of these will develop significant disability.5,6
About ACTEMRA (tocilizumab)
ACTEMRA is the first humanized IL-6 receptor-inhibiting monoclonal antibody approved for the treatment of adult patients with moderately to severely active RA who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Studies demonstrate that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, relieves both inflammation of the joints and certain systemic symptoms of RA. The extensive ACTEMRA 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.
Some people have serious infections while taking ACTEMRA, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Other serious side effects of ACTEMRA include tears (perforation) of the stomach and intestines, changes in blood test results, hepatitis B infection in those already carrying the virus, nervous system problems, and serious allergic reactions.
Common side effects with ACTEMRA include upper respiratory tract infections (common cold, sinus infections), headache, and increased blood pressure (hypertension).
Patients must tell their healthcare providers if they plan to become pregnant or are pregnant. It is not known if ACTEMRA will harm an unborn baby. Genentech has a registry for pregnant women who take ACTEMRA. Patients who are pregnant or become pregnant while taking ACTEMRA must contact the registry at 1-877-311-8972 and talk to their healthcare provider.
Patients must call their healthcare provider for medical advice about any side effects. Patients or caregivers may report side effects to the FDA at 1-800-FDA-1088. Patients or caregivers may also report side effects to Genentech at 1-888-835-2555.
For additional important safety information, including Boxed WARNINGS and Medication Guide, please visit http://www.actemra.com 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 India, Brazil, Switzerland and Australia.
Founded more than 30 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, California. For additional information about the company, please visit http://www.gene.com.
1 Cassidy JT, et al. Juvenile rheumatoid arthritis. Cassidy JT, Petty RE, eds. Textbook of pediatric rheumatology 2001:218-322.
2 Woo P. Systemic juvenile rheumatoid arthritis: diagnosis, management, and outcome. Nature Clinical Practice: Rheumatology. 2006. 2:1.
3 Symmons DP et al. Pediatric rheumatology in the United Kingdom: data from the British Paediatric Rheumatology Group National Diagnostic Register. J Rheumatology. 1996: 23: 1975-1980.
4 Fishman D et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998: 102: 1369-1376.
5 Lomater C, Gerloni V, Gattinara M, Mazotti J, Cimaz R, Fantini F, et al. Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years. J Rheumatol. 2000;27:491- 96.
6 Prieur AM, Bremard-Oury C, Griscelli C, Mozziconacci P. Prognosis of the systemic forms of juvenile chronic arthritis. Apropos of 100 cases. Arch Fr Pediatr. 1984;41:91-7.