HUMAN GENOME SCIENCES REPORTS RESULTS OF ONGOING PHASE 1
CLINICAL TRIALS OF HGS-ETR1 IN PATIENTS WITH ADVANCED CANCERS
– Results of Phase 1 clinical studies support
further evaluation of HGS-ETR1 in Phase 2 clinical trials both as a
single agent and in combination with chemotherapy –
– Data presented at 16 th EORTC-NCI-AACR
Symposium on Molecular Targets and Cancer Therapeutics –
ROCKVILLE, Maryland – September 29, 2004 – Human Genome Sciences,
Inc. (Nasdaq: HGSI) announced today that the results of ongoing Phase 1
clinical trials demonstrate the safety and tolerability of HGS-ETR1
(agonistic human monoclonal antibody to TRAIL Receptor 1) in patients
with advanced solid tumors or non-Hodgkin’s lymphoma, and support
further evaluation of HGS-ETR1 in Phase 2 clinical trials, both as a
single agent and in combination with chemotherapy.
Safety, pharmacokinetic and biological activity data from two Phase
1 studies of HGS-ETR1 were presented today at the 16th
EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics
in Geneva, Switzerland. The conference is jointly organized by the
European Organisation for Research and Treatment of Cancer (EORTC),
National Cancer Institute (NCI) and American Association for Cancer
Research (AACR).
In an oral presentation at the EORTC-NCI-AACR Symposium’s plenary
session, entitled “A
Phase 1 Clinical Trial of HGS-ETR1, an Agonistic Monoclonal Antibody to
TRAIL-R1, in Patients with Advanced Solid Tumors,” data were
presented on thirty-nine patients treated to date in an ongoing
open-label, dose-escalation clinical trial.1 The median
number of chemotherapeutic treatment regimens previously received was
two, and ranged as high as nine. The patients were enrolled into seven
cohorts (0.01, 0.03, 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg) and received
HGS-ETR1 administered intravenously on a 28-day or 14-day schedule. The
primary purpose of the study is to determine the safety, maximum
tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetics of
HGS-ETR1 in patients with relapsed or refractory advanced tumors.
Disease response also is being evaluated. Available tumor tissue
samples from patients participating in the trial will be evaluated for
expression of the TRAIL Receptor-1 protein using immunohistochemical
(IHC) techniques.
Results to date of the ongoing Phase 1 clinical trial demonstrate
that HGS-ETR1 can be administered safely and repetitively to patients
with advanced solid malignancies at doses up to and including 10 mg/kg
intravenously every 28 days. No evidence of drug-related hematologic or
hepatic toxicity has been observed at doses up to and including 10
mg/kg. The MTD has not been reached, and accrual in the trial continues
at a dose of 10 mg/kg every 14 days. Dose-proportional pharmacokinetics
were observed up to a dose of 1.0 mg/kg, with a terminal elimination
half-life of 15 days. In seven patients treated at the 10 mg/kg dose
level, the terminal elimination half-life of HGS-ETR1 was longer,
averaging about 18 days. Some preliminary evidence of biological
activity has been observed. Durable stable disease for greater than
eight months was observed in one patient with metastatic sarcoma.
Durable stable disease was observed for four months in one patient with
head-and-neck cancer and in one patient with Ewing’s sarcoma; both
patients continue on treatment.
A poster entitled “Phase
1 Study of a Fully Human Monoclonal Antibody to the Tumor Necrosis
Factor-Related Apoptosis-Inducing Ligand Receptor 1 (TRAIL-R1) in
Subjects with Advanced Solid Malignancies or Non-Hodgkin’s Lymphoma”
(Abstract #208) presented data on twenty-four patients treated to date
in an open-label, dose-escalation clinical trial currently ongoing at
two centers in Canada.2 All patients admitted to the trial
have relapsed or refractory disease and had received prior anti-cancer
treatments (chemotherapy, radiotherapy, or hormone therapy). To date,
twenty-four patients have been enrolled into five cohorts (0.01, 0.03,
0.3, 3.0, or 10.0 mg/kg) and received HGS-ETR1 administered
intravenously every 28 days. Patients continue to be enrolled into the
10 mg/kg dose cohort. The study design calls for enrollment of an
additional cohort at a dose of 20 mg/kg. Patients are treated every 28
days in the absence of disease progression or dose-limiting toxicities.
The primary objective of the trial is to evaluate the safety and
tolerability of repeated doses of HGS-ETR1 administered intravenously
in patients with advanced solid tumors or non-Hodgkin’s lymphoma. The
secondary objectives are to evaluate the pharmacokinetics of repeated
doses of HGS-ETR1 and to assess tumor response.
Results to date of the ongoing clinical trial demonstrate that
HGS-ETR1 is well tolerated with no clearly attributable toxicities to
date and that the MTD has not been reached. The median number of
treatment cycles delivered is two (1-12). Stable disease has been
observed in eight patients for greater than two cycles. Preliminary
data indicate that the pharmacokinetics of HGS-ETR1 are
dose-proportional up to 0.3 mg/kg. The trial continues to enroll
patients.
An additional poster presented at the EORTC-NCI-AACR Symposium, “Variable
Distribution of TRAIL Receptor 1 in Primary Human Tumor and Normal
Tissues” (Abstract #225), described the results of a preclinical
study designed to identify specific malignancies that are most likely
to express TRAIL Receptor 1.3 Such malignancies could be
strong candidate indications for HGS-ETR1. The study, conducted by
scientists at Human Genome Sciences in collaboration with scientists
from DakoCytomation 4 and Fox Chase Cancer Center, used a
highly specific immunohistochemical assay to evaluate TRAIL-R1 in human
tumor and normal tissue. Of the first 134 malignancies evaluated, a
total of 87 tumors (65 percent) showed some degree of TRAIL-R1 specific
staining. TRAIL-R1 specific staining was consistently weak or absent in
all 17 normal tissues assayed. Tumors of the pancreas, colon and lung
were the most likely to have substantial staining for TRAIL-R1.
Prostatic carcinomas were least likely to demonstrate TRAIL-R1
staining. The level of TRAIL-R1 protein in the colon was explored
further in 26 additional samples representative of typical neoplastic
progression. TRAIL-R1 staining distribution and intensity were
increased in malignancies of the colon as compared to benign lesions or
focal carcinomas in situ.
Roger B. Cohen, M.D., Director, Phase 1 Clinical Trials Program,
Fox Chase Cancer Center, Philadelphia, said, “The Phase 1 clinical
results we presented today demonstrate that HGS-ETR1 is well tolerated
and can be safely and repetitively administered to patients with
advanced malignancies. We have seen no evidence of drug-related
hematological or hepatic toxicity at the dose levels administered to
date. We have not reached a maximum tolerated dose, and we have seen
preliminary evidence of biological activity. Patient accrual continues
in the ongoing Phase 1 trials. Further evaluation of HGS-ETR1 is
appropriate in Phase 2 clinical trials, both as a single agent and in
combination with chemotherapy.”
David C. Stump, M.D., Executive Vice President, Drug Development,
said, “We continue to be encouraged by the results emerging from our
ongoing Phase 1 clinical trials of HGS-ETR1. The data show that
HGS-ETR1 is well tolerated in patients with advanced solid tumors or
non-Hodgkin’s lymphoma. Stable disease has been observed in a number of
patients in these studies as well. Based on the encouraging interim
clinical results from our Phase 1 studies, along with the strongly
supportive preclinical evidence1-3, 6-11, we announced at
the beginning of September that we have advanced HGS-ETR1 to a Phase 2
clinical trial in patients with relapsed or refractory non-small cell
lung cancer.5 We plan to initiate additional Phase 2
clinical trials of HGS-ETR1 in the weeks and months to come.”
Human Genome Sciences, using genomic techniques, originally
identified the TRAIL Receptor-1 protein as a member of the tumor
necrosis factor receptor super-family. The company’s own studies, as
well as those conducted by others, show that TRAIL Receptor 1 plays a
key role in triggering apoptosis, or programmed cell death, in tumors.
Human Genome Sciences took the approach of developing human monoclonal
antibodies that would bind the receptor and stimulate the TRAIL
Receptor-1 protein to trigger apoptosis in cancer cells, in much the
same way that the native TRAIL ligand (tumor necrosis factor-related
apoptosis-inducing ligand) triggers it, but with the advantage of a
longer half-life and an exclusive specificity for TRAIL Receptor 1. The
TRAIL Receptor-1 agonistic human monoclonal antibody, HGS-ETR1, was
made in a collaboration between Human Genome Sciences and Cambridge
Antibody Technology.12 The drug will be produced in the
Human Genome Sciences clinical manufacturing facilities located in
Rockville, Maryland. Human Genome Sciences holds the commercial rights
to the drug.
For more information about HGS-ETR1, see www.hgsi.com/products/ETR1.html.
Health professionals interested in more information about trials
involving HGSI products are encouraged to inquire via the Contact Us
section of the Human Genome Sciences web site, www.hgsi.com/products/request.html,
or by calling (240) 314-4400, extension 3550.
Human Genome Sciences is a company with the mission to treat and
cure disease by bringing new gene-based protein and antibody drugs to
patients.
HGS and Human Genome Sciences are trademarks of Human Genome
Sciences, Inc.
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 planned 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. 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.
###
Footnotes:
1. R.B.
Cohen, et al. “A Phase 1 Clinical Trial of HGS-ETR1, an Agonistic
Monoclonal Antibody to TRAIL-R1, in Patients with Advanced Solid Tumors.”
16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics, 2004: Oral Presentation.
2. S.J.
Hotte, et al. Phase 1 Study of a Fully Human Monoclonal Antibody to the
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor 1
(TRAIL-R1) in Subjects with Advanced Solid Malignancies or
Non-Hodgkin’s Lymphoma (NHL). 16th EORTC-NCI-AACR Symposium on
Molecular Targets and Cancer Therapeutics, 2004: Abstract #208.
3. W.
Halpern, et al. Variable Distribution of TRAIL Receptor 1 in Primary
Human Tumor and Normal Tissues. 16th EORTC-NCI-AACR Symposium on
Molecular Targets and Cancer Therapeutics, 2004: Abstract #225.
4. (HGSI Press Release) Human Genome Sciences Announces License
Agreement with DakoCytomation for Development of Pharmacogenomic
Diagnostic Assays. March 31, 2004.
5. (HGSI Press Release) Human Genome Sciences Advances Anti-Cancer Drug
to Phase 2 Clinical Development. September 8, 2004.
6. A.W. Tolcher, et al. A Phase 1 and Pharmacokinetic Study of
HGS-ETR1, A Fully Human Monoclonal Antibody to TRAIL-R1 (TRM-1), in
Patients with Advanced Solid Tumors. American Society of Clinical
Oncology Annual Meeting, 2004: Abstract #3060.
7. L.H. Le, et al. Phase 1 Study of a Fully Human Monoclonal Antibody
to the Tumor Necrosis Factor-Related Apoptosis-Inducting Ligand Death
Receptor 4 (TRAIL-R1) in Subjects with Advanced Solid Malignancies or
Non-Hodgkin’s Lymphoma. American Society of Clinical Oncology Annual
Meeting, 2004: Abstract #2533.
8. G.V. Georgakis, et al. Selective Agonistic Monoclonal Antibodies to
the TRAIL Receptors R1 and R2 Induce Cell Death and Potentiate the
Effect of Chemotherapy and Bortezomib in Primary and Cultured Lymphoma
Cells. American Society of Clinical Oncology Annual Meeting, 2004:
Abstract #6595.
9. TRAIL R2-mAb, a human agonistic monoclonal antibody to tumor
necrosis factor-related apoptosis inducing ligand receptor 2, affects
tumor growth and induces apoptosis in human tumor xenograft models in
vivo. Robin C. Humphreys, Ralph F. Alderson, Eliel Bayever, Kevin
Connolly, Gil H. Choi, Norma Lynn Fox, Gilles Gallant, Krzystof J.
Grzegorzewski, Viktor Roschke, Theodora W. Salcedo, Jing Zhang, Junli
Zhang, Vivian R. Albert. 94th AACR Annual Meeting. Abstract 642.
10. TRAIL-R2 mAb, a human agonistic monoclonal antibody to tumor
necrosis factor-related apoptosis inducing ligand receptor 2, induces
apoptosis in human tumor cells. Ralph F. Alderson, Charles E. Birse,
Kevin Connolly, Gil H. Choi, Norma Lynn Fox, Gilles Gallant, Ina Han,
Robin C. Humphreys, Ron Johnson, Palanisamy Kanakaraj, Vikram Patel,
Oxana Pickeral, Laurie Pukac, Viktor Roschke, Theodora Salcedo, Tara
Shah, Junli Zhang, Vivian R. Albert. 94th AACR Annual Meeting. Abstract
963.
11. Ashkenazi A. et al. Safety and anti-tumor activity of recombinant
soluble APO2 ligand. J Clin Inv July 1999; 104(2): 155-162.
12. (HGSI Press Release) Cambridge Antibody Technology and Human Genome
Sciences Announce Second Drug Partnership. January 8, 2002.
FOR IMMEDIATE RELEASE
CONTACTS:
David C. Stump, M.D.
Executive Vice President, Drug Development
240/314-4400
Jerry Parrott
Vice President, Corporate Communications
301/315-2777
Kate de Santis
Director, Investor Relations
301/251-6003