Tuesday August 24, 9:34 am Eastern Time
Company Press Release
British Biotech plc Announces Results of Marimastat
Study 145 in Gastric Cancer
OXFORD, England--(BUSINESS WIRE)--Aug. 24, 1999--British Biotech (Nasdaq: BBIOY - news) announces the results
of Study 145, a multi-center, pivotal Phase III clinical trial of the oral matrix metalloproteinase (MMP) inhibitor, marimastat.
This study was designed to investigate the potential benefit of marimastat on the survival of patients with inoperable gastric
cancer. These results represent the second from a programme of 10 randomized controlled trials of marimastat in a range of
solid tumors.
Key points
A randomized placebo-controlled trial of marimastat in 369 patients with inoperable gastric cancer, Study 145, has been
completed and analyzed.
The trial compared treatment of 10mg marimastat twice daily versus placebo and the data were analyzed at the
pre-defined clinical cut off when 85 per cent mortality was first recorded in one of the treatment groups.
The primary objective of this trial was to determine whether treatment with marimastat improved patient survival. At the
pre-defined clinical cut off, 22.7% of marimastat-treated patients were alive compared with 14.1% of patients receiving
placebo.
The survival benefit for marimastat-treated patients did not achieve statistical significance (p < 0.05) using the
pre-defined clinical cut off (p = 0.084). The study did not, therefore, meet its primary end-point.
However, the survival benefit in favor of marimastat has increased with continued follow-up of the trial using all data
available to date (p = 0.048).
At the pre-defined clinical cut off, patients treated with marimastat showed a statistically significant benefit compared
with placebo in the secondary end-point analysis of progression-free survival, a composite measure of tumor progression
and survival (p = 0.027).
At the pre-defined clinical cut off, a survival benefit in favor of marimastat was seen in those patients without metastases
(p = 0.033).
The safety data revealed no marked difference between marimastat and placebo other than the expected musculoskeletal
events. There was no difference in the overall level of adverse events between the groups.
Commenting on the results of Study 145, Mr John Fielding, Consultant Surgical Oncologist, Queen Elizabeth Hospital,
Birmingham, the principal Study investigator, said, ''Gastric cancer is a type of cancer that is in particular need of new
treatment. This is the first evidence from a placebo-controlled clinical trial that matrix metalloproteinase inhibitors may be
important in treating gastric cancer. In addition, the survival benefit seen with marimastat is strengthened with longer patient
follow-up.''
Dr. Elliot Goldstein, British Biotech's Chief Executive, added, ''Marimastat has shown the potential for a survival benefit in
gastric cancer, especially in longer-term follow-up of patients. This result is underpinned by a statistically significant result in an
important secondary end-point, progression-free survival. Based on our assessment of the data and discussions with
independent cancer experts we intend to consult with regulatory authorities to determine how best to proceed in gastric
cancer.''
British Biotech plc Results of Marimastat Study 145 in Gastric Cancer
British Biotech plc announces the outcome of Study 145, a pivotal Phase III clinical trial of its investigational new drug,
marimastat, in patients with inoperable gastric cancer. This trial is the second to report in a series of randomized, controlled
trials of marimastat in a range of solid tumors.
Study design and objectives
Study 145 was a randomized, double-blind, placebo-controlled study of 369 patients with inoperable gastric cancer,
conducted in 37 centers across Europe. Patients with histologically- or cytologically-proven inoperable gastric cancer were
randomly allocated to one of two treatment groups and received either 10mg of marimastat or placebo orally twice daily. To be
included in the study, patients had to have an anticipated life expectancy of greater than three months and not more than one
regimen of prior chemotherapy. The pre-defined clinical cut off of the study, at which point data were first analyzed, was when
85 per cent mortality was first recorded in one of the treatment groups.
The primary end-point was to compare the effect of marimastat against placebo as a maintenance therapy on survival in patients
with inoperable gastric cancer. Secondary end-points included progression-free survival, safety, tolerability, quality of life and
pharmacokinetics.
Enrollment commenced in October 1996 and was completed in October 1998. The study reached its pre-defined clinical cut
off when 85 per cent of the patients receiving placebo had died and the data were first analyzed at this point. Patients enrolled
in the study continue to be treated and evaluated.
Study results
Primary end-point analysis
All survival data were analyzed using Kaplan-Meier graphs applying the log rank test, with a significance level of 0.05. This is a
conventional way to evaluate such data in clinical trials. A comparison of baseline characteristics revealed that the two treatment
arms were well balanced indicating that a fair comparison between marimastat and placebo had been made. The primary
objective of this trial was to determine whether treatment with marimastat improved patient survival. At clinical cut off, 22.7%
of marimastat treated patients were alive compared with 14.1% of patients receiving placebo. The survival benefit for
marimastat-treated patients did not achieve statistical significance (p < 0.05) using data collected up to the pre-defined clinical
cut off (p = 0.084). The study did not, therefore, meet its primary end-point as defined in the protocol. However, the survival
benefit in favor of marimastat has increased with continued follow-up of the trial using all data available to date (p = 0.048).
Secondary end-point analyses
Data on progression-free survival, a composite measure of tumor growth and survival, were also analyzed using Kaplan-Meier
graphs by applying the log rank test. Patients treated with marimastat showed a statistically significant benefit compared with
placebo at the pre-defined clinical cut off (p = 0.027). Additionally, the safety data revealed no marked difference between
marimastat and placebo other than the expected musculoskeletal events. There was no difference in the overall level of adverse
events between the groups.
Other analysis
At the pre-defined clinical cut off a survival benefit was seen in favor of marimastat compared with placebo in 101 patients
without metastases (p = 0.033).
Implications of Study 145
The results from Study 145 are currently under discussion with external advisers, including clinical oncology experts. The
Company intends to consult with regulatory authorities to determine how best to proceed in gastric cancer.
Partnership discussions
British Biotech is continuing discussions with major pharmaceutical companies to seek a partner to develop and commercialize
MMPIs, including marimastat, for the treatment of cancer.
Availability of drug
Marimastat is an investigational new drug, and therefore unlicensed, and is only available to patients participating in the
marimastat clinical trial programme and not through any other means.
This news release contains forward-looking statements which reflect the Company's current expectation regarding future
events. Forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected
herein and depend on a number of factors including the success of the Company's research strategy, the applicability of the
discoveries made therein, the successful and timely completion of clinical studies and the uncertainties related to the regulatory
process.
Contact:
British Biotech plc
Tony Weir
011-44-1865-781166
or
G.A. Kraut Company
Gerard Coffey
212/696-5600 |
