Exelixis, Inc. (Nasdaq:
EXEL) presented data from its phase 2 clinical trial of XL784 in
subjects with albuminuria due to diabetic nephropathy. XL784 is a small
molecule inhibitor of ADAM-10 and MMP-2, metalloprotease enzymes that may
play a role in the pathogenesis of diabetic nephropathy and renal fibrosis.
The data were presented during a poster session (Abstract/Poster PO1030) at
the American Society of Nephrology Renal Week 2007 meeting in San
Francisco. The company previously announced that the clinical trial did not
meet its primary endpoint.
125 subjects were enrolled into this randomized, double-blind,
placebo-controlled study. XL784 (200mg once daily for 12 weeks) was
compared to placebo in subjects with macro-albuminuria who were being
treated concurrently with an angiotensin-converting enzyme inhibitor (ACEi)
or an angiotensin receptor blocker (ARB).
The primary endpoint was the reduction from baseline in the urinary
albumin to creatinine ratio (ACR) at Week 12. Proteinuria, the presence of
excess protein in the urine, is an indicator of renal disease. Albumin
excretion is a risk factor for kidney failure, stroke and cardiovascular
and all-cause mortality, particularly in patients with diabetes and/or
hypertension. Nephropathy (kidney disease) is a common problem in diabetic
patients, often leading to the need for hemodialysis or kidney transplant.
After 12 weeks of treatment with XL784 the baseline normalized ACR (end
of treatment/baseline ACR) in the XL784 group was 9.9% lower than that in
the placebo group (not significant). There was a clinically relevant mean
ACR reduction from baseline of 23% (p=0.0027) in subjects randomized to
XL784. The change in glomerular filtration rate (GFR) at Week 12 was -2.5
ml/min/1.73m2 in the XL784 group and -6.2 ml/min/1.73m2 in the placebo
group (p=0.077).
In an exploratory analysis, subjects were stratified according to dose
of ACEi and/or ARB received (as a percentage of the maximum FDA recommended
dose). The benefit of XL784 compared to placebo increased with increasing
dose of ACEi and/or ARB. In the subgroup of subjects treated with maximum
recommended doses of ACEi and/or ARB, the difference between XL784 and
placebo was 23% (p=0.13) for the primary analysis population.
XL784 was generally well-tolerated, with fewer subjects reporting
adverse events in the XL784 group (77%) than in the placebo group (85%).
Serious adverse events (SAEs) were reported by 9.5% of subjects in the
XL784 group and by 11% of subjects in the placebo group. No SAEs in the
XL784 group were considered to be related to study drug.
"We are pleased to report the data from the XL784 trial in patients
with diabetic nephropathy," said George A. Scangos, PhD, president and
chief executive officer of Exelixis. "While the trial did not meet its
primary endpoint, various subgroup analyses suggest that the compound may
have the potential to benefit patients with this disease. We submitted the
XL784 data package to GSK on October 22, 2007 and expect to communicate
future plans for XL784 once GSK has reached a decision on its interest in
further developing the compound."
About XL784
XL784 is the first small molecule compound developed by Exelixis using
its proprietary drug discovery engine. The compound is a potent inhibitor
of the ADAM-10 and MMP-2 metalloprotease enzymes, targets of significant
interest because of their important role in renal fibrosis and impairment.
XL784 was specifically optimized to be matrix metalloprotease-1 (MMP-1)
sparing, thus potentially significantly enhancing its safety profile and
enabling higher dosing compared with other previously studied
metalloprotease inhibitors. Results of single and repeat dose phase 1
clinical trials of XL784 administered orally to 70 healthy volunteers
demonstrated that XL784 has attractive safety and pharmacokinetic profiles.
About Exelixis
Exelixis, Inc. is a development-stage biotechnology company dedicated
to the discovery and development of novel small molecule therapeutics for
the treatment of cancer and other serious diseases. The company is
leveraging its fully integrated drug discovery platform to fuel the growth
of its development pipeline, which is primarily focused on cancer.
Currently, Exelixis' broad product pipeline includes investigational
compounds in phase 2 and phase 1 clinical development for cancer and renal
disease. Exelixis has established strategic corporate alliances with major
pharmaceutical and biotechnology companies, including GSK, Bristol-Myers
Squibb, Genentech, Wyeth Pharmaceuticals and Daiichi-Sankyo. For more
information, please visit the company's web site at
exelixis.
Forward Looking Statements
This press release contains forward-looking statements, including,
without limitation, statements related to the future development and
potential safety and efficacy of XL784. Words such as "may," "expect,"
"suggest," "potentially" and similar expressions are intended to identify
forward-looking statements. These forward-looking statements are based upon
Exelixis' current expectations. Forward-looking statements involve risks
and uncertainties. Exelixis' actual results and the timing of events could
differ materially from those anticipated in such forward-looking statements
as a result of these risks and uncertainties, which include, without
limitation, the results of any failure of XL784 to demonstrate safety and
efficacy in clinical testing, risks related to Exelixis' arrangement with
SEI and Exelixis' dependence on and relationship with GSK. These and other
risk factors are discussed under "Risk Factors" and elsewhere in Exelixis'
Quarterly Report on Form 10-Q for the quarter ended June 30, 2007 and
Exelixis' other filings with the Securities and Exchange Commission.
Exelixis expressly disclaims any obligation or undertaking to release
publicly any updates or revisions to any forward-looking statements
contained herein to reflect any change in Exelixis' expectations with
regard thereto or any change in events, conditions or circumstances on
which any such statements are based.
Exelixis, Inc.
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