Actemra: Roche's Novel Rheumatoid Arthritis Drug Shows Substantial Benefits for Patients in OPTION Study

Actemra: Roche's Novel Rheumatoid Arthritis Drug Shows Substantial Benefits for Patients in OPTION Study

June 15, 2007

-- New Data Supports IL-6 Receptor Inhibition as a Key
Component in Controlling Inflammation From RA


    BASEL, Switzerland, June 15 /Xinhua-PRNewswire/ --
Roche today announced significant results from 'OPTION'(1),
the first rheumatoid arthritis multinational phase III study
of Actemra (tocilizumab) outside of Japan. The data
presented at the EULAR(2) meeting in Barcelona, Spain,
showed that patients who received Actemra in combination
with methotrexate achieved rapid and significant
improvement in their signs and symptoms of rheumatoid
arthritis when compared to patients receiving methotrexate
alone.

    In the 24-week study, four times the number of patients
in the Actemra group experienced 50% improvement in disease
symptoms (ACR50(3) response) compared to the control group
(44% vs 11%). More than ten times the number of Actemra
patients achieved 70% improvement in disease signs and
symptoms (ACR70 response) compared to the control group
(22.0% vs 2.0%). In addition, 28% of patients achieved the
ultimate goal of remission(4) in the Actemra group vs only
1% of patients in the control group. 

    "The efficacy of IL-6 receptor inhibition in this
study confirms the critical role of IL-6 in the causal
pathways of rheumatoid arthritis. On this basis, the
profound clinical success observed with tocilizumab by
targeting a novel pathway is extremely encouraging as is
the opportunity for rheumatoid arthritis patients to
benefit from a potential new treatment option,"
commented lead investigator, Professor Josef Smolen. 

    "The detailed data from the OPTION study, together
with the first data from the TOWARD study announced last
week, show a great benefit for rheumatoid arthritis
patients. We look forward to further results from our
extensive multinational Phase III development programme
later this year" commented William Burns, CEO Division
Roche Pharmaceuticals. 

    Other parameters measured included C-reactive protein
(CRP), a marker of inflammation, fatigue and haemoglobin.
Patients in the 8mg/kg Actemra group showed a rapid
normalisation of the CRP levels within 2 weeks while
fatigue scores showed that patients in the Actemra group
experienced a reduction in fatigue and a rapid improvement
in haemoglobin levels. Low levels of haemoglobin are
usually associated with anaemia which makes patients feel
tired and lacking in energy. 

    About the OPTION study

    The OPTION (TOcilizumab Pivotal Trial in Methotrexate
Inadequate respONders) study was an international study
involving 623 patients with moderate to severe RA. In this
3-arm, randomized, double-blind study, patients received
tocilizumab intravenously (either 4mg/kg or 8mg/kg) every 4
weeks plus methotrexate weekly or placebo infusions plus
methotrexate weekly over a period of 6 months.

    Although higher efficacy was established at the higher
dose (ACR20, 50 and 70 scores of 59%, 44% and 22%
respectively in the 8mg/kg Actemra group), patients treated
with the lower dose of Actemra (4mg/kg) achieved ACR20, 50
and 70 scores of 48%, 32% and 12% respectively. Furthermore
there was a reduction in the Disease Activity Score (DAS)
from week 2 onwards for both the 8mg/kg (-3.43) and 4mg/kg
(-2.68) Actemra groups compared to control (-1.55).
Remission of disease was demonstrated in 28% of patients
treated with 8mg/kg of Actemra and methotrexate vs 14% of
patients treated with 4mg/kg of Actemra and methotrexate vs
1% or patients receiving methotrexate alone.

    Actemra was generally well tolerated with an adverse
event (AE) profile consistent with data reported in
previous studies(5).  

    About Actemra

    Actemra is the first humanised interleukin-6 (IL-6)
receptor inhibiting monoclonal antibody and represents a
novel mechanism of action to treat RA, a disease with a
high unmet medical need. Roche and Chugai are collaborating
on a phase III clinical development programme in RA running
outside Japan, with more than 4000 patients enrolled in 41
countries including several European countries and the USA.
In Japan, Actemra was launched in June 2005 as a therapy for
Castleman's disease and in April 2006 filed for the
additional indications of rheumatoid arthritis and
systemic-onset juvenile idiopathic arthritis.

    About rheumatoid arthritis

    Rheumatoid arthritis is a progressive, systemic
autoimmune disease characterized by chronic inflammation of
multiple joints and fatigue as well as the possibility of
osteoporosis, anaemia, and lung, skin and liver effects.
This inflammation causes pain, stiffness and swelling,
resulting in loss of joint function due to destruction of
the bone and cartilage, often leading to progressive
disability. Further, as chronic inflammation continues,
there may be shortening of life expectancy as a result of
effects on major organ systems. After 10 years, less than
50% of patients can continue to work or function normally
on a day to day basis. RA affects more than 21 million
people worldwide. 

    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(R) (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. Actemra is the result of
research collaboration by Chugai and is being co-developed
globally with Chugai. Additional projects creating a rich
pipeline include compounds in Phase I, II and III clinical
trials. Notably, ocrelizumab, a fully humanised anti-CD20
antibody, is just entering phase III development for RA.

    About Roche

    Headquartered in Basel, Switzerland, Roche is one of
the world's leading research-focused healthcare groups in
the fields of pharmaceuticals and diagnostics. As the
world's biggest biotech company and an innovator of
products and services for the early detection, prevention,
diagnosis and treatment of diseases, the Group contributes
on a broad range of fronts to improving people's health and
quality of life. Roche is the world leader in in-vitro
diagnostics and drugs for cancer and transplantation, a
market leader in virology and active in other major
therapeutic areas such as autoimmune diseases,
inflammation, metabolism and central nervous system. In
2006 sales by the Pharmaceuticals Division totalled 33.3
billion Swiss francs, and the Diagnostics Division posted
sales of 8.7 billion Swiss francs. Roche employs
approximately 75,000 worldwide and has R&D agreements
and strategic alliances with numerous partners, including
majority ownership interests in Genentech and Chugai.
Additional information about the Roche Group is available
on the Internet at http://www.roche.com .

    All trademarks used or mentioned in this release are
protected by law.

    Further information
    - Roche & Autoimmune diseases:
http://www.roche.com/med_events_mb1106

    References:

    (1) OPTION refers to the tOcilizumab Pivotal Trial in
methotrexate
        Inadequate respONders

    (2) European League Against Rheumatism

    (3) The ACR response is a standard assessment used to
measure patients'
        responses to anti-rheumatic therapies, devised by
the American College 
        of Rheumatology (ACR). It requires a patient to
have a defined 
        percentage reduction in a number of symptoms and
measures of their 
        disease. For example, a 20%, 50% or 70% level of
reduction (the 
        percentage of reduction of RA symptoms) is
represented as ACR20, ACR50 
        or ACR70. An ACR70 response is exceptional for
existing treatments and 
        represents a significant improvement in a patient's
condition.

    (4) Disease activity is measured by a Disease Activity
Score (DAS), where
        low disease activity is defined as DAS 28 less than
or equal to 3.2 
        and remission is defined as DAS 28 less than or
equal to 2.6

    (5) Maini RN, Taylor PC, Szechinski J et al., on behalf
of the CHARISMA
        Study Group. Double-blind randomised controlled
clinical trial of the
        interleukin-6 receptor antagonist, tocilizumab, in
European patients 
        with rheumatoid arthritis who had an incomplete
response to 
        methotrexate. Arthritis Rheum. 2006
Sep;54(9):2817-29.

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    Further information
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http://www.roche.com/med_events_mb1106

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