AstraZeneca Announces Top-Line Results of OSKIRA-4 Phase IIb Study of Fostamatinib as a Monotherapy for Rheumatoid Arthritis

    AstraZeneca Announces Top-Line Results of OSKIRA-4 Phase IIb Study of
            Fostamatinib as a Monotherapy for Rheumatoid Arthritis

PR Newswire

SOUTH SAN FRANCISCO, Calif., Dec. 13, 2012

SOUTH SAN FRANCISCO, Calif., Dec. 13, 2012 /PRNewswire/ --AstraZeneca today
announced top-line results of OSKIRA-4, a Phase IIb monotherapy study of
fostamatinib, the first kinase inhibitor with selectivity for SYK (spleen
tyrosine kinase) in development as an oral treatment for rheumatoid arthritis
(RA).

OSKIRA-4 was a six month study evaluating improvements in signs and symptoms
of RA in 280 patients who had never previously used a disease-modifying
anti-rheumatic drug (DMARD), were DMARD intolerant or had an inadequate
response to DMARDs and were randomised to receive fostamatinib as a
monotherapy, adalimumab as a monotherapy, or placebo. Three dose regimens of
fostamatinib were evaluated in OSKIRA-4: 100mg twice daily, 100mg twice daily
for a month followed by 150mg once daily, and 100mg twice daily for a month
followed by 100mg once daily.

OSKIRA-4 had two primary objectives – a superiority comparison to placebo at 6
weeks and a non-inferiority analysis against adalimumab monotherapy at 24
weeks as measured by change from baseline in DAS28 score (a composite endpoint
assessing signs and symptoms of RA).

In the OSKIRA-4 study, fostamatinib as a monotherapy met the first primary
objective, showing a statistically significant superior DAS28 score change
from baseline compared to placebo at 6 weeks at the 100mg twice daily dose and
the 100mg twice daily for a month followed by 150mg once daily dose, but not
at the 100mg twice daily for a month followed by 100mg once daily dose.

The OSKIRA-4 study did not meet its second primary objective as all
fostamatinib monotherapy doses were inferior to adalimumab monotherapy at week
24 based on DAS28. The adalimumab monotherapy ACR20 result at the 24 week
endpoint was 59%.

The safety and tolerability findings for fostamatinib as reported in the
OSKIRA-4 study were generally consistent with that previously observed in the
TASKi Phase II programme.

Martin Mackay, President of AstraZeneca Research and Development said: "This
Phase IIb dose finding study was designed to evaluate the effect of
fostamatinib independent of methotrexate and to inform the further development
of fostamatinib as a monotherapy treatment for RA. A more comprehensive
assessment of the benefit/risk profile of fostamatinib used in combination
with a DMARD is being undertaken in the pivotal studies that form the OSKIRA
Phase III programme which are on track to report in the first half of 2013,
and would form the basis of regulatory submissions."

Regulatory filings in the US and EU for use in combination with a DMARD based
on the OSKIRA Phase III programme, are expected in the second half of 2013.

A more detailed analysis of the OSKIRA-4 findings will be published in due
course.

About the OSKIRA programme
Ongoing Phase III trials in the OSKIRA (Oral Syk Inhibition in Rheumatoid
Arthritis) programme, include three pivotal studies assessing the efficacy and
safety of fostamatinib; two 12-month studies examining the effect of
fostamatinib on patients responding inadequately to DMARDs including
methotrexate (OSKIRA-1, OSKIRA-2); a six-month study assessing the effect of
fostamatinib on patients who have previously responded inadequately to an
anti-TNF therapy (OSKIRA-3); and a long-term extension study looking at the
ongoing safety and tolerability of fostamatinib (OSKIRA-X). The three pivotal
studies have as their primary endpoint the proportion of patients with ACR20
compared to placebo (ACR20 = American College of Rheumatology 20% response
criteria). The OSKIRA-1 study also has a co-primary endpoint of change from
baseline to week 24 in modified total Sharp score (mTSS), an x-ray endpoint
assessing structural progression.

These Phase III studies are expected to be completed in the first half of
2013.

For more information about OSKIRA-4 visit:
http://clinicaltrials.gov/ct2/show/NCT01264770

About Fostamatinib
Fostamatinib (previously referred to as R788), is the first kinase inhibitor
with selectivity for SYK in development as an oral treatment for rheumatoid
arthritis. Fostamatinib blocks signalling in multiple cell types involved in
inflammation and tissue degradation in rheumatoid arthritis and it is
hypothesized that it may hinder key steps in the progression of the disease.
In February 2010, AstraZeneca and Rigel Pharmaceuticals announced a worldwide
license agreement whereby AstraZeneca will develop and commercialise
fostamatinib.

About Rheumatoid Arthritis (RA)
RA is a painful, systemic, chronic inflamatory disease which can cause damage
to the joints and vital organs as well as affecting other parts of the
musculoskeletal system such as connective tissues, muscles and tendons. The
disease affects approximately one in 100 people worldwide.

If not adequately treated, RA is a major cause of disability and is associated
with reduced life expectancy. In the US alone the total annual societal cost
of RA is estimated to amount to $39.2 billion, with even greater indirect
costs to individuals and society including costs from diminished work
capacity, loss of productivity, loss in earnings and loss in tax
contributions.

About Rigel Pharmaceuticals
Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL) is a clinical-stage drug development
company that discovers and develops novel, small-molecule drugs for the
treatment of inflammatory and autoimmune diseases, as well as muscle
disorders. Rigel's pioneering research focuses on intracellular signaling
pathways and related targets that are critical to disease mechanisms. Rigel's
productivity has resulted in strategic collaborations with large
pharmaceutical partners to develop and market its product candidates. Current
product development programs include fostamatinib, an oral SYK inhibitor that
is in Phase III clinical trials for rheumatoid arthritis with its partner
AstraZeneca; R343, an inhaled SYK inhibitor for asthma and R333, a topical
JAK/SYK inhibitor for discoid lupus – both of which have commenced Phase II
clinical trials; and R548, an oral JAK3 inhibitor for the treatment of
transplant rejection and other immune disorders. Visit www.rigel.com.

About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business with a
primary focus on the discovery, development and commercialisation of
prescription medicines for gastrointestinal, cardiovascular, neuroscience,
respiratory and inflammation, oncology and infectious disease. AstraZeneca
operates in over 100 countries and its innovative medicines are used by
millions of patients worldwide. For more information please visit:
www.astrazeneca.com

Rigel Pharmaceuticals Forward Looking Statement
This press release contains "forward-looking" statements, including, without
limitation, statements related to the progress of the development of
fostamatinib, partnered with AstraZeneca, and the results of OSKIRA-4, as well
as statements related to dates for clinical filings and publications. Any
statements contained in this press release that are not statements of
historical fact may be deemed to be forward-looking statements. Words such as
"hypothesized," "will," "may," "expect," and similar expressions are intended
to identify these forward-looking statements. These forward-looking statements
are based upon Rigel's current expectations and involve risks and
uncertainties. There are a number of important factors that could cause
Rigel's results to differ materially from those indicated by these
forward-looking statements, including, without limitation, the timing and
success of clinical trials and the potential problems that may arise in the
development and approval process, market competition, risks associated with
Rigel's corporate partnerships, as well as other risks detailed from time to
time in Rigel's reports with the Securities and Exchange Commission, including
its Quarterly Report on Form 10-Q for the quarter ended September 30, 2012.
Rigel does not undertake any obligation to update forward-looking statements
and expressly disclaims any obligation or undertaking to release publicly any
updates or revisions to any forward-looking statements contained herein.

CONTACTS

Media Enquiries
Esra Erkal-Paler +44 20 7604 8030
Vanessa Rhodes +44 20 7604 8037

Investor Enquiries UK
James Ward-Lilley +44 20 7604 8122 mob: +44 7785 432613
Karl Hård +44 20 7604 8123 mob: +44 7789 654364
Nicklas Westerholm +44 20 7604 8124 mob: +44 7585 404950

Investor Enquiries US
Ed Seage +1 302 886 4065 mob: +1 302 373 1361

Rigel Investor Enquiries
Raul Rodriguez +1 650 624 1302, Email: invrel@rigel.com

Rigel Media Enquiries
Susan C. Rogers, Alchemy Consulting, Inc. +1 650 430 3777, Email:
susan@alchemyemail.com

SOURCE Rigel Pharmaceuticals, Inc.

Website: http://www.rigel.com
 
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