Data Published Today Reveal That Novel Oral Therapy Fostamatinib Demonstrates Positive Response in Rheumatoid Arthritis PatientsBy Astrazeneca, PRNE
Tuesday, September 21, 2010
Phase II Study Published in the New England Journal of Medicine
LONDON and SAN FRANCISCO, September 22, 2010 - AstraZeneca's (LSE: AZN) new oral syk inhibitor, fostamatinib (R788),
recently in-licensed from Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL),
significantly improved outcomes of patients with rheumatoid arthritis (RA)
who responded inadequately to ongoing treatment with methotrexate (MTX),
according to phase II study data published in The New England Journal of
In the six-month phase IIb study completed by Rigel, known as TASKi2, 67%
of patients taking fostamatinib 100mg twice daily achieved the primary
efficacy endpoint (ACR 20)* at six months, which was significantly higher
than placebo. Thirty-six percent of patients achieved an ACR 20 response
after just one week. Speed of onset may be an important factor in RA because
permanent joint damage can occur when the disease is active. The most common
adverse events included diarrhea and upper respiratory infection.
"In this study, we saw a significant clinical benefit in this rheumatoid
arthritis population and a manageable safety profile," said Mark C. Genovese,
Division of Rheumatology, Stanford University, Palo Alto, CA. "Based on the
data, further study of fostamatinib as an oral agent for the treatment of
patients with rheumatoid arthritis is certainly warranted."
Patients in the study had active RA despite treatment with MTX alone, and
were given either fostamatinib 100mg twice daily (bid), fostamatinib 150mg
once daily (qd), or placebo. Significant clinical benefits were reported in
both fostamatinib groups in the key efficacy endpoints of the American
College of Rheumatology (ACR) patient assessment criteria and Disease
Activity Score (DAS) 28** remission criteria.
After six months: - The ACR 20 response was achieved by significantly more patients in both the fostamatinib 100mg bid group and the fostamatinib 150mg qd group (67% and 57% respectively) than the placebo group (35%, p<0.001). - The ACR 50* response rates were 43%, 32% and 19% for the fostamatinib 100mg bid group, 150mg qd group and placebo group respectively (p<0.01). The ACR 70* response rates were 28%, 14% and 10% for the fostamatinib 100mg bid group, 150mg qd group and placebo group respectively (p<0.001 for fostamatinib 100mg bid, p=0.34 for fostamatinib 150 mg qd). - In addition, the DAS 28 remission rate was significantly higher in both the fostamatinib 100mg bid group and the fostamatinib 150mg qd group (31% and 21% respectively), compared to the placebo group (7%, p<0.01).
The published data indicates that the most common drug-related adverse
events in the study were diarrhea (19% in 100mg bid group, 12% in the 150mg
qd group and 3% in the placebo group), upper respiratory infection (15%, 7%
and 7% respectively) and neutropenia (6%, 7% and 1% respectively).
Hypertension (BP>140/90) occurred more frequently in fostamatinib treated
patients than placebo (29% across both fostamatinib groups compared to 17% in
placebo group) as had been previously reported. The hypertension generally
occurred within the first few weeks of therapy and was responsive to
conventional anti-hypertensive medications.
There were a similar proportion of patients who had at least one adverse
event (AE) among the placebo group and the fostamatinib groups (65%).
Ninety-four percent of eligible patients enrolled in an ongoing long-term
open label extension study. The low rate of withdrawals is additional
evidence that the adverse events were manageable in the patients studied.
AstraZeneca plans to commence the phase III clinical trial programme for
fostamatinib shortly. The phase III programme, called OSKIRA (Oral Syk
Inhibition in Rheumatoid Arthritis), is expected to begin in the second half
* The ACR 20 response criteria is defined as greater than or equal to 20%
improvement from baseline in both tender and swollen joints, and greater than
or equal to 20% improvement in three of five measures: pain, acute phase
reactant, physical function, patient and physician global assessment. ACR 50
and ACR 70 assess greater than or equal to 50% improvement and greater than
or equal to 70% improvement in those areas respectively.
** DAS 28 is a measure of the activity of Rheumatoid Arthritis assessing 28
joint counts in the body
Fostamatinib (previously referred to as R788), is the first oral syk
inhibitor in development as a novel therapeutic approach for RA. It is
thought to reversibly block signalling in multiple cell types involved in
inflammation and tissue degradation in RA.
In February 2010, AstraZeneca and Rigel Pharmaceuticals announced a
worldwide license agreement whereby AstraZeneca will develop and
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease,
which causes damage to the joints and other organs, affecting approximately 1
in 100 people. It is a major cause of disability and is also associated with
reduced life expectancy, especially if not adequately treated.
About the TASKi2 Study Design
TASKi2 was a 6 month, multi-center, randomized, double-blind, placebo
controlled, parallel dose clinical trial involving 457 RA patients in the
U.S., Latin America and Europe who had active RA despite treatment with MTX
alone. Approximately 1/3 of the patients (n=152) studied received 100mg of
fostamatinib orally bid. Another third received 150mg of the study drug qd
and the final third were given placebo to be taken orally bid or qd (total
placebo n=153). Throughout the study all patients continued to receive their
stable dose of MTX.
AstraZeneca is a global, innovation-driven biopharmaceutical business
with a primary focus on the discovery, development and commercialisation of
prescription medicines. As a leader in gastrointestinal, cardiovascular,
neuroscience, respiratory and inflammation, oncology and infectious disease
medicines, AstraZeneca generated global revenues of US $32.8 billion in 2009.
For more information please visit: www.astrazeneca.com.
Rigel is a clinical-stage drug development company that discovers and
develops novel, small-molecule drugs for the treatment of
inflammatory/autoimmune, muscle and metabolic diseases. 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 (R788), an oral syk inhibitor that is expected to enter phase
III clinical trials for rheumatoid arthritis in 2010, and R343, an inhaled
syk inhibitor that is in clinical trials for asthma.
Rigel Forward-Looking Statements
This press release contains "forward-looking" statements, including,
without limitation, statements related to plans to pursue further clinical
development of R788 (fostamatinib), including the timing thereof. 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
"estimate," "anticipate" 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, risks associated with the timing and success
of clinical trials and other risks detailed from time to time in Rigel's SEC
reports, including its Quarterly Report on Form 10-Q for the quarter ended
June 30, 2010. 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.
Media Contacts: Tracy Knudsen, AstraZeneca, Mobile: +32-472-900-803, Email: tracy.knudsen at astrazeneca.com; Raul Rodriguez, Rigel Office: +1-650-624-1302, Email: invrel at rigel.com; Susan C. Rogers, Alchemy Consulting, Inc. (for Rigel), Office: +1-650-430-3777, Email: susan at alchemyemail.com
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