AstraZeneca today announced the enrollment of the first patient in
the phase III clinical development program for fostamatinib, a novel
oral syk inhibitor. The phase III program, called OSKIRA (Oral Syk
Inhibition in Rheumatoid Arthritis), is designed to investigate
fostamatinib as a treatment for rheumatoid arthritis (RA) in patients
with an inadequate response to disease modifying anti-rheumatic drugs
(DMARDs), including methotrexate (MTX).
The OSKIRA clinical trial
program will include three pivotal phase III studies assessing the
efficacy and tolerability of fostamatinib; two 12-month studies
examining the effect of fostamatinib on patients responding inadequately
to DMARDs including MTX, and a six-month study assessing the effect of
fostamatinib on patients who have previously responded inadequately to
anti-TNF therapy. The fostamatinib program will also include long-term
safety extension studies involving more than 2,000 of the patients
recruited during the course of the phase II and III programmes.
“We
are delighted that the OSKIRA clinical trial program for fostamatinib
has begun,” said Anders Ekblom, AstraZeneca’s Executive Vice President
of Global Medicines Development. “Patients with rheumatoid arthritis
currently have limited treatment options after they stop responding
adequately to DMARDs or anti-TNF therapy, and we are hopeful that
fostamatinib may represent a novel alternative for patients to help
manage their condition beyond this stage.”
All three pivotal
studies start with a six-month double-blind, randomised,
placebo-controlled period, and the two 12-month studies also include a
six-month active-extension period. The primary outcome measures across
the three studies include ACR 20* response rate at six months, and one
of the 12-month studies also includes the change in structural
progression at six months as a primary endpoint. Two dose regimens of
fostamatinib will be evaluated in the phase III programme; a 100mg twice
daily regimen and a second regimen investigating 100mg twice daily for
four weeks followed by a maintenance dose of 150mg once daily.
Fostamatinib,
previously referred to as R788, is the first oral syk inhibitor in
development, and as such, represents a novel therapeutic approach for
RA. A phase II programme has recently been completed, which
demonstrated positive results in patients with rheumatoid arthritis who
were responding inadequately to ongoing treatment with MTX. This
six-month study data, known as TASKi2, was recently published in the
online edition of the New England Journal of Medicine on September 22,
2010.
The first anticipated regulatory filings based on the
OSKIRA programme are planned for 2013. Fostamatinib was in-licensed by
AstraZeneca from Rigel Pharmaceuticals, Inc. in February 2010.
