XBiotech Presents Pivotal Phase III Data Showing Xilonix(TM) Demonstrated Significant Clinical Response in Advanced Colorectal Cancer Patients Refractory to Further Treatment
(Thomson Reuters ONE) -
* Improved clinical response seen for multiple symptoms associated with
disease progression and overall survival, with notable lack of toxicity
* Xilonix is the first antibody therapy to neutralize biological activity of
interleukin-1 alpha (IL-1alpha), a potent anti-inflammatory signaling
molecule known to promote the growth and spread of tumors
* Xilonix granted accelerated review by the European Medicines Agency (EMA);
an approval decision could come as early as fourth quarter 2016
AUSTIN, Texas, July 02, 2016 (GLOBE NEWSWIRE) -- XBiotech Inc. (NASDAQ:XBIT),
developer of next-generation True Human(TM) antibody therapies, today presented
positive results from a pivotal Phase III trial of Xilonix(TM), the company's
lead monoclonal (IgG1k) antibody immunotherapy for the treatment of advanced
colorectal cancer (CRC). In the study, Xilonix-treated patients with advanced
disease and multiple symptoms known to inversely correlate with overall survival
experienced a 76% relative increase in clinical response rate (CRR), a novel
measure of anti-cancer activity, after 8 weeks of therapy compared to placebo
(33% vs. 19%, respectively; p=.0045). In addition, clinical response correlated
with improved overall survival. Among responders (in both treatment and placebo
arms), clinical response was associated with a 2.7-fold increase in overall
survival (11.5 versus 4.2 months in responders vs. non-responders,
respectively). Overall survival was not compared between treatment arms because
after 8 weeks, all patients were eligible to receive study drug. Treatment with
Xilonix was well tolerated, with an adverse event profile comparable to placebo.
The data were presented at the 18th European Society of Medical Oncology (ESMO)
World Congress on Gastrointestinal Cancer in Barcelona, Spain.
The study's primary endpoint, CRR, was developed in collaboration with the
European Medicines Agency (EMA) Scientific Advice Working Group as a means to
determine efficacy of Xilonix as an anti-cancer therapy in patients with
advanced colorectal cancer. The CRR measured debilitating symptoms (pain,
fatigue, appetite loss and muscle loss) that are key indicators of health status
and are associated with poor prognosis for survival. (1, 2, 3, 4, 5, 6)
"In this first-of-its-kind study, not only did treatment with Xilonix
demonstrate clinical benefit but it was also very well-tolerated, suggesting
Xilonix has the potential to meet the real and urgent need for more effective,
less toxic therapies for patients with advanced colorectal cancer," said Dr.
Tamas Hickish, Chair of the Xilonix European Phase III Study and Consultant
Medical Oncologist, Dorset Cancer Centre, Visiting Professor, Bournemouth
University, UK. "In addition, this study provides evidence that novel endpoints
based on symptom recovery can serve as a predictor of overall survival benefit
and thus may be used to evaluate an anti-tumor agent in this disease."
In addition to increased overall survival, responders gained more lean body mass
compared to non-responders (p<0.0007), had reduced fatigue and pain (p<0.001)
and improved appetite (p<0.001). Control of thrombocytosis and systemic
inflammation (IL-6), which are known prognosticators of overall survival, were
also significantly improved in responders vs. non-responders (p<0.0002 and
p<0.0007, respectively).
There was a notable lack of toxicity associated with Xilonix treatment in the
study. The most common adverse events (AEs) reported were abdominal pain,
peripheral edema, fatigue, anemia, constipation, decrease in weight, asthenia,
decreased appetite and nausea. The majority of these events were characterized
as mild to moderate and appeared to be related to the underlying disease. The
prevalence of AEs was similar in both treatment and placebo groups. While the
study was not powered to demonstrate a difference in serious adverse events
(SAEs) between treatment and placebo groups, there was a 26% relative risk
reduction of SAEs in the treatment arm vs. placebo (p=0.062), a unique and
notable finding.
"There is an urgent need for new forms of anti-tumor, disease-modifying cancer
therapies that effectively control disease while being less toxic," said John
Simard, XBiotech Founder, President and Chief Executive Officer. "We believe
these data demonstrate that our True Human monoclonal antibody targeting
interleukin-1 alpha has the potential to meet this critical need."
Study Methodology
In the double-blind placebo-controlled Phase III study, 309 patients were
randomized (2:1) to receive Xilonix plus best supportive care (BSC) versus
placebo plus BSC. Study participants had failed all available chemotherapy and
had metastatic disease with one or more symptoms of metabolic dysfunction and
functional impairment (i.e., elevated systemic inflammation, unintentional
weight loss, pain, fatigue, anorexia). Patients were required to have an Eastern
Cooperative Oncology Group (ECOG) function status of only 1 or 2. Elderly
patients (>70 years of age) were eligible as well, in contrast to many studies
of anti-cancer therapies in advanced disease.
The study's primary endpoint measured CRR after 8 weeks of therapy. This novel
endpoint was developed in consultation with the EMA, which has provided a
regulatory path to encourage and expedite the development of anti-cancer agents
that improve patient health status while prolonging life. These guidelines
enable development of anti-cancer agents based on an effect that improves
debilitating symptoms in patients, particularly where the effect is the result
of an anti-tumor mechanism and the clinical measures are considered
prognosticators for overall survival.(7)
CRR was assessed using dual-energy X-ray absorptiometry to determine lean body
mass (LBM) and using the standard European Organization for Research and
Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30) to capture
patients' own assessment of their fatigue, pain and anorexia from baseline to
week 8. To be classified as responders, patients had to maintain or improve LBM
and maintain or improve in at least two of the three categories of pain, fatigue
and anorexia. Secondary endpoints evaluated paraneoplastic thrombocytosis and
systemic inflammation, both known correlates for survival in colorectal cancer.
Median overall survival was also assessed. Patients receiving placebo were
allowed to receive study drug after completion of the 8-week protocol, therefore
overall survival was not compared between arms. Rather, the overall survival
analysis compared responders vs. non-responders.
About Colorectal Cancer
Colorectal cancer is the second leading cause of malignancy in the
industrialized world.(8) Because the incidence of colorectal cancer increases
with economic development and aging, incidence is rising worldwide.(9) In
Europe, approximately 470,000 patients will be diagnosed with colorectal cancer
this year, and half will progress and ultimately succumb to the
disease.(10) Disease progression is associated with significant morbidity,
functional impairment and failure of multiple therapies, often with substantial
toxicities. People with advanced disease are thus symptomatic and often unable
to tolerate further treatment-related side effects, leaving an urgent need for
more effective, less toxic therapies for these patients.
About Xilonix(TM) and Interleukin-1 alpha (IL-1alpha)
Xilonix(TM) is the first monoclonal antibody to specifically target and
neutralize interleukin-1 alpha (IL-1alpha), one of the most potent inflammatory
signaling molecules. The IL-1 pathway in general, and IL-1alpha in particular,
is a desirable target for anti-cancer therapy because of its potential role in
both local and systemic effects of cancer.(11,12) IL-1alpha in the tumor
microenvironment is known to promote angiogenesis (the growth and spread of
tumors), as well as mediate symptoms such as metabolic dysregulation (e.g., loss
of weight and muscle mass), fatigue and anxiety associated with advanced cancer.
About True Human(TM) Therapeutic Antibodies
Unlike previous generations of antibody therapies, XBiotech's True Human(TM)
antibodies are derived without modification from individuals who possess natural
immunity to certain diseases. With discovery and clinical programs across
multiple disease areas, XBiotech's True Human antibodies have the potential to
harness the body's natural immunity to fight disease with increased safety,
efficacy and tolerability.
The first of these therapies, Xilonix(TM), for advanced colorectal cancer, is in
Phase III clinical trials in the United States with a Fast Track designation by
the U.S. Food and Drug Administration (FDA). In Europe, Xilonix Phase III
clinical trials have been completed and the therapy is under accelerated review
following the validation of its Market Authorization Application by the European
Medicines Agency (EMA).
About XBiotech
XBiotech is a fully integrated global biosciences company dedicated to
pioneering the discovery, development and commercialization of therapeutic
antibodies based on its True Human(TM) proprietary technology. XBiotech
currently is advancing a robust pipeline of antibody therapies to redefine the
standards of care in oncology, inflammatory conditions and infectious diseases.
Headquartered in Austin, Texas, XBiotech also is leading the development of
innovative biotech manufacturing technologies designed to more rapidly, cost-
effectively and flexibly produce new therapies urgently needed by patients
worldwide. For more information, visit www.xbiotech.com.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements, including declarations
regarding management's beliefs and expectations that involve substantial risks
and uncertainties. In some cases, you can identify forward-looking statements by
terminology such as "may," "will," "should," "would," "could," "expects,"
"plans," "contemplate," "anticipates," "believes," "estimates," "predicts,"
"projects," "intend" or "continue" or the negative of such terms or other
comparable terminology, although not all forward-looking statements contain
these identifying words. Forward-looking statements are subject to inherent
risks and uncertainties in predicting future results and conditions that could
cause the actual results to differ materially from those projected in these
forward-looking statements. These risks and uncertainties are subject to the
disclosures set forth in the "Risk Factors" section of certain of our SEC
filings. Forward-looking statements are not guarantees of future performance,
and our actual results of operations, financial condition and liquidity, and the
development of the industry in which we operate, may differ materially from the
forward-looking statements contained in this press release. Any forward-looking
statements that we make in this press release speak only as of the date of this
press release. We assume no obligation to update our forward-looking statements
whether as a result of new information, future events or otherwise, after the
date of this press release.
__________________________
(1)Hong, DS, Hui D, Bruera E, et al. MABp1, a first-in-class true human antibody
targeting interleukin 1alpha in refractory cancer: an open-label, phase 1 dose-
escalation and expansion study. Lancet Oncol. 2014;15(6):656-666.
(2)Braun DP, Gupta D, Grutsch JF, Staren ED. Can changes in health related
quality of life scores predict survival in stages III and IV colorectal cancer?
Health Qual Life Outcomes. 2011 Aug 3;9:62. doi: 10.1186/1477-7525-9-62.
(3)Diouf M, et al. The added value of quality of life (QoL) for prognosis of
overall survival in patients with palliative hepatocellular carcinoma. J
Hepatol. 2013 Mar;58(3):509-21. doi: 10.1016/j.jhep.2012.11.019. Epub 2012 Nov
22.
(4)Gupta D, Braun DP, Staren ED, Markman M. Longitudinal health-related quality
of life assessment: implications for prognosis in ovarian cancer. J Ovarian Res.
2013 Mar 8;6(1):17. doi: 10.1186/1757-2215-6-17.
(5)Ediebah DE, et al. Does change in health-related quality of life score
predict survival? Analysis of EORTC 08975 lung cancer trial. Br J Cancer. 2014
May 13;110(10):2427-33. doi: 10.1038/bjc.2014.208. Epub 2014 Apr 17.
(6)Gupta D, Braun DP, Staren ED. Prognostic value of changes in quality of life
scores in prostate cancer. BMC Urol. 2013 Jul 10;13:32. doi:
10.1186/1471-2490-13-32.
(7)Guideline on the evaluation of anticancer medicinal products in man,13
December 2012. EMA/CHMP/205/95/Rev.4. Oncology Working Party.
(8)Lozano R, et al. Global and regional mortality from 235 causes of death for
20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of
Disease Study 2010. Lancet 2012;380: 2095e128.
(9)United European Gastroenterology
(UEG). https://www.ueg.eu/press/releases/ueg-press-release/article/europe-is-
falling-behind-america-in-the-fight-against-colorectal-cancer-due-to-low-
screening-uptake/. Accessed April, 2016.
(10)EuropaColon. http://www.europacolon.com/crcstatistics.php?Action=Crcstatisti
cs. Accessed April, 2016.
(11)Apte RN, Voronov E. Interleukin-1 a major pleiotropic cyto-kine in tumor-
host interactions. Can Biol. 2002;12:277-290.
(12)Dinarello CA. Interleukin-1alpha neutralisation in patients with cancer.
Lancet Oncol. 2014;15(6):552-553.
Media liaison U.S.
Mariann Caprino
+1 917 242 1087
Media liaison ex-U.S.
Jonathan Kearney
+44 20 8618 2755; Mobile: +44 7725 925 841
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Source: XBiotech, Inc via GlobeNewswire
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Datum: 02.07.2016 - 12:10 Uhr
Sprache: Deutsch
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