Data Demonstrated ACTEMRA(R) (tocilizumab) Significantly Inhibited Progression of...

Data Demonstrated ACTEMRA(R) (tocilizumab) Significantly Inhibited Progression
of Structural Joint Damage in Rheumatoid Arthritis Patients

- Additional data reinforce long-term efficacy of ACTEMRA across a broad
range of rheumatoid arthritis patient populations -

NUTLEY, N.J., June 10 /PRNewswire/ -- One-year data from the two-year Phase
III LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage)
study demonstrated that a greater proportion of rheumatoid arthritis (RA)
patients treated with ACTEMRA(R) (tocilizumab), a novel interleukin-6 (IL-6)
receptor inhibitor, in combination with methotrexate, experienced a
significant inhibition in the progression of structural joint damage compared
with patients treated with methotrexate alone. These data will be presented
at the 10th Annual Congress of the European League Against Rheumatism (EULAR)
in Copenhagen, Denmark, along with additional studies that support the use of
ACTEMRA as a long-term treatment option for patients with moderately to
severely active RA.

In the one-year LITHE study, disease remission (DAS28(1) <2.6) was
demonstrated in 30 percent and 47 percent of patients treated with ACTEMRA 4
mg/kg and 8 mg/kg, respectively, compared with 8 percent of patients treated
with placebo plus methotrexate.

"Inhibiting RA from progressing further by achieving disease remission
provides real-life benefits to patients, while at the same time helping them
maintain day-to-day function," said Joel Kremer, M.D., lead investigator of
the LITHE study and Director of Research at The Center for Rheumatology in
Albany, New York. "The LITHE study also demonstrated the efficacy of ACTEMRA
even in patients with a relatively long disease duration, which suggests that
it may be an effective treatment option for many RA patients."

Additionally, the one-year LITHE study results showed that patients treated
with ACTEMRA (4 mg/kg or 8 mg/kg) plus methotrexate experienced a significant
inhibition in the progression of structural joint damage, as measured by the
change in the mean Genant-modified Sharp score(2), compared with patients
treated with methotrexate plus placebo (0.29, 0.34 versus 1.1, respectively;
p<0.001). In addition, data demonstrated that there were significantly more
patients treated with ACTEMRA (4 mg/kg or 8 mg/kg) who experienced no
progression of structural joint damage from baseline compared with
methotrexate plus placebo-treated patients (81%, 85% versus 67%, p less than
or equal to 0.0001), as measured by the Genant-modified Sharp score. Most
patients also experienced improved physical function following treatment with
ACTEMRA, as measured by the Health Assessment Questionnaire Disability Index
(HAQ-DI).(3)

An additional study to be presented at the Congress is an interim analysis
from two ongoing, long-term ACTEMRA extension studies consisting of patients
who had completed one of four 24-week controlled studies of ACTEMRA as
monotherapy or with DMARDs. Patients were treated with ACTEMRA 8 mg/kg every
four weeks to assess the efficacy of ACTEMRA for up to two-and-a-half years
across three patient populations: DMARD-IR (inadequate response), anti-TNF-IR
and DMARD-naive patients (predominantly methotrexate-naive patients and
patients without prior failure to methotrexate). The analysis showed that
long-term efficacy was maintained in all three patient populations treated
with ACTEMRA, as measured by ACR response rates and DAS28 scores.

ACTEMRA monotherapy was proven to be statistically superior to methotrexate in
ACR20, ACR50 and ACR70 responses(4) (at six months), according to results of a
post-hoc analysis of the AMBITION (Actemra versus Methotrexate double-Blind
Investigative Trial In mONotherapy) study also to be presented at the
Congress. The study showed that nearly 70 percent of patients receiving
ACTEMRA monotherapy (8 mg/kg) achieved ACR20 compared with 52.5 percent of
patients receiving methotrexate alone. More patients treated with ACTEMRA
achieved ACR50 (44.1 percent) and ACR70 (28 percent) compared with the
methotrexate group, 33.5 percent and 15.1 percent, respectively.

"The findings from these studies relating to the inhibition of IL-6 reinforce
ACTEMRA as a viable treatment option for patients with RA," said Kenneth
Bahrt, M.D., Global Medical Director, Autoimmunity, Roche.

About the LITHE Study
The LITHE trial, a three-arm, randomized, double-blind, placebo-controlled
study, was designed to evaluate the efficacy and safety of ACTEMRA (4 mg/kg or
8 mg/kg) plus methotrexate compared with placebo plus methotrexate in RA
patients for the prevention of structural joint damage, improvement in
physical function and disease signs and symptoms over two years. Patients
received either ACTEMRA intravenously every four weeks plus methotrexate
weekly or placebo infusions every four weeks plus methotrexate weekly.

Data from the LITHE study also showed that patients treated with ACTEMRA (8
mg/kg or 4 mg/kg) plus methotrexate experienced a reduction in disease signs
and symptoms at one year compared with patients treated with placebo plus
methotrexate. At 52 weeks, 56 percent, 36 percent and 20 percent of RA
patients treated with ACTEMRA 8 mg/kg plus methotrexate achieved ACR20, ACR50
and ACR70, respectively, and 47 percent, 29 percent and 16 percent of patients
in the ACTEMRA 4 mg/kg arm achieved these ACR scores, respectively. In
contrast, 25 percent, 10 percent and 4 percent of patients in the control
group achieved ACR20, ACR50 and ACR70, respectively.

The study evaluated more than 1,200 patients at 137 sites in 15 countries,
including the United States. ACTEMRA was generally well tolerated. The
adverse events reported most frequently in the ACTEMRA arms of the LITHE study
were serious infections.

About the Long-Term Extension Studies
The interim analysis was from two ongoing, open-label, long-term extension
studies consisting of patients who had completed one of four 24-week
controlled studies of ACTEMRA as monotherapy or with DMARDs. Patients were
treated with ACTEMRA 8mg/kg every four weeks to assess the efficacy of ACTEMRA
for up to two-and-a-half years across three patient populations: DMARD-IR
(inadequate response), anti-TNF-IR and DMARD-naive patients, (predominantly
methotrexate-naive patients and patients without prior failure to
methotrexate). In DMARD-IR patients, a significant proportion achieved a 50
or 70 percent improvement in their disease signs and symptoms at 132 weeks,
66.7 percent (ACR50) and 43.9 percent (ACR70), and maintained ACR70 response
for 24 consecutive weeks. Similar patterns of response were achieved with the
anti-TNF-IR and DMARD-naive groups.

These multi-center studies evaluated more than 2,500 patients throughout the
world. ACTEMRA was generally well tolerated. The adverse events reported most
frequently in the ACTEMRA arms of the studies were upper respiratory tract
infection, nasopharyngitis, headache and hypertension.

About the AMBITION Study
AMBITION, a two-arm, randomized, double-blind, placebo-controlled study, was
designed to evaluate the non-inferiority and subsequent superiority of ACTEMRA
monotherapy in patients with RA compared with methotrexate alone at 24 weeks.
The main study examined patients who had not received methotrexate for at
least six months beforehand and were randomized to receive either ACTEMRA (8
mg/kg) intravenously every four weeks plus placebo capsules weekly or placebo
infusions every four weeks plus methotrexate weekly. The post-hoc analysis
evaluated patients who were methotrexate- or DMARD-naive.

The study evaluated 673 patients from 252 sites in 18 countries, including the
United States. ACTEMRA was generally well tolerated. The adverse events
occurring in the AMBITION study were infections and gastrointestinal
disorders.

About ACTEMRA(R) (tocilizumab)
ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting
monoclonal antibody being studied for the treatment of RA. 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 effects of RA. The extensive clinical development program conducted
by Roche includes five Phase III clinical studies and has enrolled more than
4,000 patients in 41 countries, including the United States. The five Phase
III studies are completed and have reported meeting their primary endpoints.
ACTEMRA is currently under review by the U.S. Food and Drug Administration
(FDA).

ACTEMRA is part of a co-development agreement between Roche and Chugai
Pharmaceutical Co. In June 2005, ACTEMRA was launched by Chugai in Japan as a
therapy for Castleman's disease; in April 2008, additional indications for
rheumatoid arthritis, juvenile idiopathic arthritis and systemic-onset
juvenile idiopathic arthritis were also approved in Japan. ACTEMRA (known as
RoACTEMRA in Europe), was also recently approved in the European Union,
Switzerland and India.

The serious adverse events reported in ACTEMRA clinical studies include
serious infections, gastrointestinal perforations and hypersensitivity
reactions including anaphylaxis. The most common adverse events reported in
clinical studies were upper respiratory tract infection, nasopharyngitis,
headache, hypertension and increased ALT. Increases in liver enzymes (ALT and
AST) were seen in patients; these increases were generally mild and
reversible, with no evidence of hepatic injuries. Laboratory changes,
including increases in lipids (total cholesterol, LDL, HDL, triglycerides) and
decreases in neutrophils and platelets, were seen in patients without
association with clinical outcomes. Treatments that suppress the immune
system, such as ACTEMRA, may cause an increase in the risk of malignancies.

About IL-6
IL-6 is a common protein found in all joints in the body and is a natural
substance that can raise inflammation. Everyone has IL-6 in their body, but
people with RA may have too much. When approved, ACTEMRA will be the first and
only medication to specifically target IL-6 in patients with RA.

About Rheumatoid Arthritis
RA is a progressive, systemic autoimmune disease characterized by inflammation
of the membrane lining in the joints. This inflammation causes a loss of joint
shape and function, resulting in pain, stiffness and swelling, ultimately
leading to irreversible joint destruction and disability. Characteristics of
RA include redness, swelling, pain and movement limitation around joints of
the hands, feet, elbows, knees and neck that leads to loss of function. In
addition, the systemic symptoms of RA include fatigue, decreased hemoglobin,
osteoporosis and may contribute to shortening life expectancy by affecting
major organ systems. After 10 years, less than 50 percent of patients can
continue to work or function normally on a daily basis. RA affects more than
21 million people worldwide with approximately 1.3 million adults affected in
the United States.

About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S.
pharmaceuticals headquarters of the Roche Group, one of the world's leading
research-oriented healthcare groups with core businesses in pharmaceuticals
and diagnostics. For more than 100 years in the U.S., Roche has been committed
to developing innovative products and services that address prevention,
diagnosis and treatment of diseases, thus enhancing people's health and
quality of life. For additional information about the U.S. pharmaceuticals
business, visit our website http://www.rocheusa.com. Product and treatment
information for U.S. healthcare professionals is available at
www.RocheExchange.com.

(1) The Disease Activity Score (DAS)28 is a combined index that measures
disease activity in patients with RA. It combines information from 28 tender
and swollen joints (range 0-28), erythrocyte sedimentation rate, and a general
health assessment on a visual analog scale. The level of disease activity is
interpreted as low (DAS28 less than or equal to 3.2), moderate (3.25.1). DAS28<2.6 corresponds to being in
remission according to the criteria of the American College of Rheumatology.
(2) The Genant-modified Sharp score focuses on 14 specific sites for evidence
of bone erosion and 13 sites for narrowing of the joint space; both key
measures of ongoing structural damage to the joints. Erosion scores are
assigned to each of the specified sites, with 0 representing "no erosion" and
3.5 representing "destruction of the joint." Joint space narrowing scores are
assigned to each of the specified sites, with 0 representing "no narrowing"
and 4 representing "total loss of the joint space." Increases in the scores
indicate the extent of additional erosion, joint space narrowing or overall
structural damage (both scores combined) that have occurred since treatment
began.
(3) The Health Assessment Questionnaire Disability Index (HAQ-DI) is a 20-item
questionnaire that asks about physical functioning within eight categories
(dressing and grooming, arising, eating, walking, hygiene, reach, grip and
daily activities). The ability to perform each category is measured on a scale
0 to 3 (0 = no difficulty, 1 = some difficulty, 2 = much difficulty or with
assistance, and 3 = unable).
(4) ACR20, ACR50, ACR70 represent the percentage of reduction (20%, 50%, 70%)
in certain RA symptoms and measures the number of tender and swollen joints,
pain, patient's and physician's global assessments and certain laboratory
markers.

Contacts: Lindsay Rocco
Roche
Office: 973-235-2802
Cell: 862-596-1304
Lindsay.Rocco@roche.com

SOURCE Roche

Lindsay Rocco of Roche, Office, +1-973-235-2802, Cell, +1-862-596-1304,
Lindsay.Rocco@roche.com