- Results of first reported clinical trial of any antibody to TRAIL
receptor 2 in combination with chemotherapy, presented at AACR-NCI-EORTC
International Conference -
- Preclinical study demonstrating synergy of TRAIL receptor antibodies with
chemotherapy highlighted by meeting organizers in press activities -
ROCKVILLE, Md., Oct. 24 /PRNewswire-FirstCall/ -- Human Genome
Sciences, Inc. (Nasdaq: HGSI) today announced that HGS-ETR2 (lexatumumab)
was safe and well tolerated in combination with four different standard
chemotherapy regimens in a Phase 1b clinical trial in patients with a wide
range of cancer types. Objective responses were reported for two patients,
and stable disease was observed in 22 patients. The trial was the first
reported human study of an antibody to TRAIL receptor 2 in combination with
chemotherapy. The results were presented today at the AACR-NCI-EORTC
International Conference on Molecular Targets and Cancer Therapeutics in
San Francisco.
(Logo: http://www.newscom.com/cgi-bin/prnh/20010612/HGSLOGO )
The company also presented preclinical data demonstrating that HGS-ETR1
(mapatumumab) and HGS-ETR2 in combination with chemotherapy synergistically
enhanced anti-tumor activity in cholangiocarcinoma (cancer of the bile
ducts). In a xenograft model of cholangiocarcinoma, the results
demonstrated that HGS- ETR1 and either co-treatment or pre-treatment with
cisplatin and gemcitabine were more effective than chemotherapy or HGS-ETR1
alone.
"The clinical and preclinical results presented today add to a growing
body of data showing that our agonistic antibodies to TRAIL receptors 1 and
2 offer a targeted mechanism of cancer-cell death that can be administered
safely in combination with a variety of proven chemotherapies," said Gilles
Gallant, B. Pharm., Ph.D., Vice President, Clinical Research - Oncology,
HGS. "The data suggest that both pre-treatment and co-treatment with
chemotherapy may be effective approaches to the use of TRAIL receptor
antibodies for the treatment of cancer."
About the Results of the Phase 1b Trial of HGS-ETR2
In the first reported clinical trial of a TRAIL receptor 2 agonist in
combination with chemotherapy, 41 patients with a wide range of solid
malignancies received HGS-ETR2 plus a full-dose regimen of chemotherapy
(gemcitabine, pemetrexed, doxorubicin or FOLFIRI). Four to seven patients
in each chemotherapy cohort received HGS-ETR2 intravenously at doses of
either 5 mg/kg or 10 mg/kg.
The results showed that HGS-ETR2 in combination with full-dose
chemotherapy was generally safe and well tolerated. Objective responses
were reported for two patients (a colorectal cancer patient in the FOLFIRI
arm, and a small-cell lung cancer patient in the doxorubicin arm). Stable
disease was observed in 22 patients. Overall, the nature and severity of
adverse events were consistent with the underlying disease and known safety
profile of the chemotherapeutic regimens. The pharmacokinetics of HGS-ETR2
were not influenced by the chemotherapeutic agents, nor did HGS-ETR2 affect
the pharmacokinetics of gemcitabine, doxorubicin or irinotecan. Further
studies of HGS-ETR2 in combination with chemotherapy are warranted.
"The results of the Phase 1b study of HGS-ETR2 show that it is well
tolerated and can be repetitively administered in combination with standard
chemotherapy agents in patients with a variety of advanced solid
malignances," said Norma Lynn Fox, Ph.D., Senior Director, Clinical
Research, HGS. "We were encouraged by the observation of objective
responses in two patients and stable disease in more than 20 patients, a
number of whom remained on treatment for more than five months before
progression of disease."
About the Preclinical Results in Cholangiocarcinoma
Results were also presented from preclinical studies that evaluated the
ability of HGS-ETR1 and HGS-ETR2 to kill cancer cells and inhibit tumor
growth as single agents and in combination with chemotherapy agents:
cisplatin, gemcitabine or 5-fluorouracil. Efficacy was measured using cell
toxicity assays in cholangiocarcinoma cell lines (in vitro) and in a
xenograft cholangiocarcinoma tumor model (in vivo).
The in vitro study showed that HGS-ETR1 or HGS-ETR2 combined with
either a pre-treatment or a co-treatment chemotherapy regimen induced
additive or synergistic cytotoxicity. Co-treatment with the triplet
combination of cisplatin, gemcitabine and either HGS-ETR1 or HGS-ETR2 was
more effective than either single agent alone in all cell lines, with most
triplet combinations inducing greater than 90 percent cell toxicity. In a
xenograft model of cholangiocarcinoma, the combination of HGS-ETR1,
cisplatin and gemcitabine significantly inhibited tumor growth, including
tumor regression observed at a dose of 8 mg/kg of cisplatin.
About the HGS TRAIL Receptor Antibodies
HGS-ETR1 and HGS-ETR2 are agonistic human monoclonal antibodies that
directly induce cancer-cell death by specifically binding to and activating
the proteins known as TRAIL receptors 1 and 2, respectively. Using genomic
techniques, HGS originally identified the TRAIL receptor-1 and TRAIL
receptor- 2 proteins. The HGS-ETR1 and HGS-ETR2 antibodies were generated
by HGS through collaboration with Cambridge Antibody Technology. HGS is
developing HGS-ETR1 and HGS-ETR2 as potential treatments for a broad range
of cancers.
GlaxoSmithKline (GSK) has exercised its option under a June 1996
agreement to develop and commercialize HGS-ETR1 jointly with HGS. Under the
terms of the agreement, GSK and HGS will share equally in Phase 3/4
development costs, and will share equally in sales and marketing expenses
and profits of any product commercialized.
About Human Genome Sciences
The mission of HGS is to apply great science and great medicine to
bring innovative drugs to patients with unmet medical needs.
The HGS clinical development pipeline includes novel drugs to treat
hepatitis C, lupus, anthrax disease, cancer and other immune-mediated
diseases. The Company's primary focus is rapid progress toward the
commercialization of its two key lead drugs, Albuferon(R) (albinterferon
alfa- 2b) for hepatitis C and LymphoStat-B(R) (belimumab) for lupus. Phase
3 clinical trials of both drugs are ongoing.
ABthrax(TM) (raxibacumab) is in late-stage development for the
treatment of anthrax disease, and the Company is on track to begin the
delivery in 2008 of 20,000 doses of ABthrax to the Strategic National
Stockpile under a contract entered into with the U.S. Government in June
2006. Other HGS drugs in clinical development include two TRAIL receptor
antibodies for the treatment of cancers.
For more information about HGS, please visit the Company's Web site at
http://www.hgsi.com. To view the AACR-NCI-EORTC poster presentation reporting
results of the Phase 1b clinical trial of HGS-ETR2 in combination with
chemotherapy, click here. To view the poster presentation reporting results
of the preclinical studies of HGS-ETR1 and HGS-ETR2 with chemotherapy in
cholangiocarcinoma, click here. Health professionals or patients interested
in HGS-ETR1 or HGS-ETR2 clinical trials or other studies involving HGS
products may inquire via the Contact Us section of the Company's web site,
http://www.hgsi.com/products/request.html, or by calling us at (301) 610-5790,
extension 3550.
Safe Harbor Statement
This announcement contains forward-looking statements within the
meaning of Section 27A of the Securities Act of 1933, as amended, and
Section 21E of the Securities Exchange Act of 1934, as amended. The
forward-looking statements are based on Human Genome Sciences' current
intent, belief and expectations. These statements are not guarantees of
future performance and are subject to certain risks and uncertainties that
are difficult to predict. Actual results may differ materially from these
forward-looking statements because of the Company's unproven business
model, its dependence on new technologies, the uncertainty and timing of
clinical trials, the Company's ability to develop and commercialize
products, its dependence on collaborators for services and revenue, its
substantial indebtedness and lease obligations, its changing requirements
and costs associated with facilities, intense competition, the uncertainty
of patent and intellectual property protection, the Company's dependence on
key management and key suppliers, the uncertainty of regulation of
products, the impact of future alliances or transactions and other risks
described in the Company's filings with the Securities and Exchange
Commission. In addition, the Company will continue to face risks related to
animal and human testing, to the manufacture of ABthrax and to FDA
concurrence that ABthrax meets the requirements of the ABthrax contract. If
the Company is unable to meet the product requirements associated with the
ABthrax contract, the U.S. government will not be required to reimburse the
Company for the costs incurred or to purchase any ABthrax doses. Existing
and prospective investors are cautioned not to place undue reliance on
these forward-looking statements, which speak only as of today's date.
Human Genome Sciences undertakes no obligation to update or revise the
information contained in this announcement whether as a result of new
information, future events or circumstances or otherwise.
SOURCE Human Genome Sciences, Inc.
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Related links:
http://www.hgsi.com
Photo Notes:
NewsCom: http://www.newscom.com/cgi-bin/prnh/20010612/HGSLOGO
AP Archive: http://photoarchive.ap.org
PRN Photo Desk, photodesk@prnewswire.com
http://www.prnewswire.com/comp/121115.html /
CONTACT:
Jerry Parrott, Vice President, Corporate
Communications, +1-301-315-2777, Kate de Santis, Director,
Investor Relations, +1-301-251-6003, both of Human Genome
Sciences, Inc.
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