Actemra significantly improves debilitating symptoms of RA in patients who have inadequate response to standard therapy

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Novel drug Actemra significantly improves the debilitating symptoms of

Rheumatoid Arthritis in patients who have an inadequate response to standard

therapy

http://www.pharmalive.com/News/index.cfm?articleid=524698 & categoryid=40

Pivotal Phase III OPTION study published today in The Lancet

Patients with rheumatoid arthritis treated with ACTEMRA (tocilizumab)

experienced a rapid and significant reduction in the signs and symptoms of their

disease, according to a study published in this week's issue of The Lancet.

Results from the OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate

respONders) trial - a major Phase III international study - demonstrated that

rheumatoid arthritis (RA) patients not only achieved greater improvement of

symptoms but also a higher quality-of-life with ACTEMRA, an innovative

interleukin-6 (IL-6) receptor inhibitor, compared with methotrexate, a commonly

used RA treatment.

" Results of this pivotal study convincingly demonstrate that tocilizumab can

effectively and rapidly diminish the painful and debilitating effects of

rheumatoid arthritis, " said f Smolen, M.D., lead investigator of the OPTION

trial and Professor of Medicine at the Department of Internal Medicine at the

Medical University of Vienna, Austria. " These trial findings are significant

because we know that many rheumatoid arthritis patients continue to experience

symptoms of joint pain and stiffness, physical disability and fatigue despite

treatment with existing therapies. "

Rheumatoid arthritis 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 and ultimately leading to irreversible joint

destruction and disability. In addition, the systemic symptoms of RA include

fatigue, anaemia, osteoporosis and may contribute to shortening life expectancy

by affecting major organ systems. Sadly after 10 years, less than 50% of

patients can continue to work or function normally on a daily basis.

ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting

monoclonal antibody and it represents a novel mechanism of action to treat RA.

Research has shown that reducing the activity of IL-6, one of several key

cytokines involved in the inflammatory process, reduces inflammation of the

joints and relieves certain systemic effects of RA.

About the OPTION Study

In the OPTION trial, a three-arm, double-blind, controlled Phase III study, 623

patients were randomized to receive ACTEMRA intravenously (either 4mg/kg or

8mg/kg) every four weeks plus methotrexate weekly or placebo infusions plus

methotrexate weekly. The study was conducted in 73 trial sites in 17 countries

outside the United States.

At 24 weeks, 58.5% of ACTEMRA patients (8mg/kg) achieved a 20% reduction in RA

symptoms (ACR20)1, compared with 26.5% of patients in placebo plus metrotrexate

patients. In the study, 43.9% of patients treated with ACTEMRA (8 mg/kg) plus

methotrexate achieved at least a 50% (ACR50) reduction in symptoms compared to

10.8% of patients receiving placebo and methotrexate; ACR70 was achieved in 22%

of the treatment group versus 2% in the control group. A rapid decrease in

disease activity (DAS28)2 was seen as early as two weeks in a greater proportion

of patients treated with ACTEMRA plus methotrexate, with 27.5% achieving

clinical remission (DAS28~ 2.6) by 24 weeks.

Additionally, results showed that 80% of patients in the ACTEMRA (8mg/kg) plus

methotrexate group responded with moderate to good improvements in RA symptoms,

according to the EULAR response criteria3, compared with 35% for those treated

with placebo and methotrexate at 24 weeks.

The OPTION trial also assessed physical function and quality-of-life at baseline

and every four weeks thereafter. Patients receiving ACTEMRA achieved

significantly greater improvement in areas of fatigue and mental function at 24

weeks, and achieved normal levels of hemoglobin and C-reactive protein (CRP), a

marker of inflammation due to RA, compared with patients receiving placebo plus

methotrexate.

About ACTEMRA

ACTEMRA is the result of research collaboration by Chugai and is being

co-developed globally with Chugai. ACTEMRA is the first humanized interleukin-6

(IL-6) receptor-inhibiting monoclonal antibody. An extensive clinical

development program of five Phase III trials was designed to evaluate clinical

findings of ACTEMRA. Three other studies are completed and have reported meeting

their primary endpoints. A fifth trial, a two-year study called LITHE

(TociLIzumab safety and THE prevention of structural joint damage), is currently

underway and is expected to report preliminary first-year data in 2008. ACTEMRA

is awaiting approval in the United States and Europe. In Japan, ACTEMRA was

launched by Chugai in June 2005 as a therapy for Castleman's disease; in April

2006, additional indications for rheumatoid arthritis and systemic-onset

juvenile idiopathic arthritis were also filed in Japan.

ACTEMRA is generally well tolerated. The overall safety profile of ACTEMRA is

consistent across all global clinical studies. The most common, non-serious,

adverse events reported are upper respiratory tract infection, nasopharyngitis,

headache and hypertension. As with other biological disease modifying

anti-rheumatic drugs (DMARDs), serious infections and hypersensitivity reactions

including a few cases of anaphylaxis, have been reported in some patients

treated with ACTEMRA. Increases in liver transaminases (ALT and AST) were seen

in some patients; these increases were generally mild and reversible, with no

hepatic injuries or any observed impact on liver function.

About Roche in rheumatoid arthritis One of the most important drivers for growth

at Roche over the next few years is expected to be the company's emerging

franchise in autoimmune diseases with rheumatoid arthritis as the first

indication. Following the launch of MabThera (rituximab) there are a number of

projects in development, potentially allowing Roche to build on further

opportunities. MabThera is the first and only selective B-cell therapy for RA,

providing a fundamentally different treatment approach by targeting B cells, one

of the key players in the pathogenesis of RA. ACTEMRA is Roche's second novel

medicine and is a humanised monoclonal antibody to the interleukin-6 (IL-6)

receptor, inhibiting the activity of IL-6 , a protein that plays a major role in

the RA inflammation process. Additional projects creating a rich pipeline

include compounds in Phase I, II and III clinical trials. Notably, ocrelizumab,

a humanised anti-CD20 antibody, has entered phase III development for RA.