BASEL. Switzerland. 7th November 2007 The innovative newrheumatoid arthritis medicate Actemra (tocilizumab) has been shown tosignificantly improve the signs and symptoms of rheumatoidarthritis (RA) in patients who failed to achieve an adequateresponse to traditional disease modifying agents (DMARDs). Excitingnew data from the TOWARD1 study being presented as a late breaker,at the American College of Rheumatology (ACR) Annual ScientificMeeting in Boston. November 6-11 beef up the acquire of tacklingRA through the inhibition of the IL-6 pathway.
In the TOWARD trial. 61% of patients in the Actemra plus DMARDgroup achieved a 20% reduction in RA symptoms (ACR202 response)compared with only 25% of patients in the control group. Around onein three patients achieved clinical remission in the Actemra group,as assessed using DAS28 <2.63. These results are consistent withthe results of another Actemra trial the OPTION4 study which werepreviously reported and which will be the affect of furtherpresentations at ACR. The OPTION study showed that 59% of patientsin the Actemra treatment arm experienced a 20% reduction in RAsymptoms (ACR 20 response) versus only 27% of patients in thecontrol group.
"We are very encouraged by the findings of this new TOWARD datawhich declare that Actemra plus DMARDs demonstrates significantimprovement in RA symptoms compared with DMARDs alone," said MarkC. Genovese. M. D. lead study investigator of the TOWARD trial andassociate Professor of Medicine at Stanford University School ofMedicine. "These data further open the efficacy of Actemra andconfirm that inhibiting the interleukin-6 (IL-6) receptor is anovel method of reducing RA symptoms."
"These results show that remission rates achieved with Actemracompare favourably with current RA therapies indicating themedicine's potential to become a very effective new treatmentoption," said Dr. Urs Schleuniger. Head of Inflammatory Diseases,Roche. "Findings from the TOWARD and OPTION studies will be move ofthe application to Regulatory Authorities that we intend to submitby the end of the year."
The TOWARD trial a two-arm double-blind placebo-controlledstudy was designed to evaluate the safety and efficacy of Actemraplus DMARDs compared to placebo plus DMARDs in RA patients. Patients were randomized to acquire either Actemra intravenously(8mg/kg) every four weeks plus DMARDs weekly or placebo infusionsplus DMARDs weekly. The multicentre study treated 1,216 patients at130 trial sites in 18 countries including the U. S.
At 24 weeks significantly more patients achieved a 20%. 50% and70% (ACR20. ACR50 and ACR70) reduction of symptoms with Actemraplus DMARDs compared to the hold back group. The ACR20. ACR50 andACR70 was achieved in 61%. 38% and 21% respectively of Actemraplus DMARDs patients versus 25%. 9% and 3% respectively in theplacebo plus DMARDs arm. Disease remission was demonstrated in 30%of Actemra patients (DAS28 <2.6) compared with 3 % of patientstreated with only DMARDs.
In the OPTION trial. 623 patients were randomized to receiveActemra intravenously (either 4mg/kg or 8mg/kg) every four weeksplus methotrexate weekly or placebo infusions plus methotrexateweekly. OPTION a three-arm double-blind controlled study,evaluated the safety and efficacy of Actemra plus methotrexatecompared to placebo plus methotrexate in RA patients. The study wasconducted in 73 trial sites in 17 countries outside the UnitedStates. At 24 weeks significantly more patients achieved a 20%. 50%and 70% (ACR20. ACR50 and ACR70) reduction of symptoms with Actemraplus methotrexate compared to the hold back arm. Fifty nine per cent,44% and 22% respectively of patients treated with Actemra(8mg/kg) plus methotrexate achieved ACR20. ACR50 and ACR70 comparedwith 27%. 11% and 2% respectively in the control group. Diseaseremission was demonstrated in 28% of Actemra patients (DAS28<2.6) compared with 1 % of patients treated with methotrexatealone.
Other parameters measured in both studies included levels ofC-reactive protein (CRP) a marker of inflammation fatigue andhaemoglobin. Patients on Actemra showed a rapid normalisation ofthe CPR levels within two weeks and a rapid improvement inhaemoglobin levels. According to both studies patients treatedwith Actemra plus DMARDs experienced greater improvements inquality of life and answer measures including fatigue andphysical and mental functions compared to placebo plus DMARDs.
Actemra was generally come up tolerated in both studies. The mostcommon adverse events reported more frequently in the Actemra armwere upper respiratory tract infections headache nasopharyngitisand hypertension. As with other disease modifying
Other studies The TOWARD1 and OPTION2 trials are two of fivephase III clinical studies designed to evaluate Actemra as apotential new treatment for RA. Two others. emit5 and AMBITION6-are completed and undergo met their primary chew over endpoints. Anadditional phase III trial is ongoing; the two-year study calledLITHE7 and this chew over is expected to report data later in 2008. Allstudies are expected to be presented at upcoming medical meetingsin 2008.
Actemra is the first humanised interleukin-6 (IL-6) receptorinhibiting monoclonal antibody and represents a novel mechanism ofaction to treat RA a disease with a high unmet medical be. Theoverall safety compose observed in the global studies of Actemra isconsistent and Actemra is generally come up tolerated. The mostfrequent adverse events reported have included upper respiratorytract infections headache nasopharyngitis and hypertension. Aswith other biological disease modifying anti-rheumatic drugs(DMARDs) serious infections have been reported in some patientstreated with Actemra. Roche and Chugai are collaborating on a phaseIII clinical development programme in RA running outside Japan,with more than 4000 patients enrolled in 41 countries includingseveral European countries and the USA. In lacquer. Actemra waslaunched in June 2005 as a therapy for Castleman's disease and inApril 2006 filed for the additional indications of rheumatoidarthritis and systemic-onset juvenile idiopathic arthritis.
About rheumatoid arthritis Rheumatoid arthritis is aprogressive systemic autoimmune disease characterized by chronicinflammation of multiple joints and degenerate as come up as thepossibility of osteoporosis anaemia and lung skin and livereffects. This inflammation causes pain stiffness and swelling,resulting in loss of joint answer due to destruction of the boneand cartilage often leading to progressive disability. advance aschronic inflammation continues there may be shortening of lifeexpectancy as a prove of effects on major organ systems. After 10years less than 50% of patients can continue to work or functionnormally on a day to day basis. RA affects more than 21 millionpeople worldwide.
About Roche in rheumatoid arthritis One of the most importantdrivers for growth at Roche over the next few years is expected tobe the company's emerging certify in autoimmune diseases withrheumatoid arthritis as the first indication. Following the launchof MabThera (rituximab) there are a be of projects indevelopment potentially allowing Roche to build on furtheropportunities. MabThera is the first and only selective B-celltherapy for RA providing a fundamentally different treatmentapproach by targeting B cells one of the key players in thepathogenesis of RA. Actemra is Roche's second novel medicine and isa humanised monoclonal antibody to.
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