|
2003/OB/19B
|
Oxford
BioMedica Receives Approval from GTAC for Metxia®
to Enter Clinical Trials in Pancreatic Cancer
Oxford BioMedica
plc announced today that it has received approval from the
UK’s Gene Therapy Advisory Committee (“GTAC”)
for MetXia to enter a two-stage Phase I/II clinical trial
in patients with pancreatic cancer. Two leading clinical centres
in Liverpool and Leicester have supported this regulatory
application and plan to commence recruitment before the end
of the year.
The trial will
be an open label study and will initially recruit six patients
to assess the safety of MetXia and to identify the optimal
dose for the second stage. In the second part of the trial,
the cyclophosphamide prodrug will be gradually escalated to
identify a maximum tolerated dose. Up to 21 patients will
be recruited and endpoints include safety, clinical response
and time to disease progression.
MetXia
is also being investigated in breast cancer patients and a
second Phase I/II trial in breast cancer is ongoing. The broadening
application of MetXia into pancreatic cancer is an important
development for this novel anticancer agent. The ongoing Phase
I/II breast cancer trial continues to support our initial
clinical findings that MetXia is safe, well tolerated and
offers potential clinical benefit. In the proposed pancreatic
cancer study MetXia will be delivered directly to the pancreatic
tumour via an intra-arterial catheter together with the cyclophosphamide
prodrug. Unlike oral administration of cyclophosphamide used
in the breast cancer trials, this strategy avoids the initial
metabolism of cyclophosphamide in the liver, thereby maximising
its localised activation in the pancreatic tumour. This clinical
protocol, therefore, could enhance the potential efficacy
of MetXia.
Pancreatic
cancer is amongst the most aggressive with median survival
time of only 6-12 months from diagnosis for inoperable cancers.
Current treatment options are primarily based on the chemotherapeutic
agents 5-fluorouracil and, more recently, gemcitabine. However,
these have a minimal effect on median survival underlining
the need for novel therapeutic strategies. Given the short
survival times and the lack of therapeutic options for this
disease, positive data from this trial could lead to accelerated
approval for MetXia in this indication.
Commenting
on this news, Chief Executive Professor Alan Kingsman said:
"This
is the first in a series of applications of MetXia following
on from the successful Phase I/II trials in late-stage breast
cancer patients. Success in pancreatic cancer should accelerate
MetXia’s commercial development.”
-
ends - |
Return to the News
| Notes
| 1. |
Oxford
BioMedica plc |
| |
Oxford
BioMedica (LSE: OXB) is a biopharmaceutical
company specialising in the development
of gene-based products for a range of unmet
medical needs with an emphasis on new cancer
products, which combine novel mechanisms
of action with very low side effects, and
innovative neurotherapy products, which
address large and, in several areas, untapped
markets. The products are all protected
by multiple patents comprising a total intellectual
property portfolio of some 69 patent families,
which represents one of the broadest patent
estates in the field.
In
addition to its technical research skill-base,
Oxford BioMedica has in-house clinical,
regulatory and manufacturing know-how. The
development pipeline includes two novel
anti-cancer products in clinical trials
and a gene-based treatment for Parkinson’s
disease, which is in late preclinical studies.
TroVax®,
Oxford BioMedica’s lead cancer immunotherapy
product, is in Phase II trials for colorectal
cancer.
Further
Phase II trials are planned for breast and
renal cancer. MetXia®, Oxford
BioMedica’s lead gene-based cancer
therapeutic, is based on a highly engineered
retrovirus gene delivery system expressing
a specific human cytochrome P450 gene.
Oxford
BioMedica has a wholly-owned subsidiary
in San Diego, USA. Oxford BioMedica has
corporate collaborations with Wyeth, Intervet,
Aliga Pharmaceuticals, Amersham, Arius Research
and Viragen.
|
| |
|
2. |
MetXia® gene therapy for cancer
A common strategy for the treatment of cancer
is to administer cytotoxic (or cell killing)
drugs in an attempt to destroy the tumour.
Cyclophosphamide is one of a group of drugs
that is taken by the patient in the form of
an inactive prodrug. The prodrug travels through
the body to the liver where enzymes convert
it to the active, cytotoxic form. This approach
affects the whole body and leads to the familiar
adverse side effects of cancer chemotherapy
because the cytotoxic drug destroys normal
cells on its way from the liver to the tumour.
In addition, because the activating enzymes
are present only in the liver, high doses
of prodrug must be given to achieve therapeutic
levels of the cytotoxic drug at the tumour
site. Often the therapeutic effect is compromised
by the toxicity.
Oxford
BioMedica’s MetXia addresses these
problems by delivering a specific human
cytochrome P450 gene (CYP2B6) directly to
the tumour using a highly engineered retrovirus
gene delivery system. Once incorporated
into the genetic material of the tumour
cells, this gene produces the liver enzyme
that converts the cyclophosphamide pro-drug
to its active form within the tumour. The
aim is to achieve high concentrations of
activated cyclophosphamide locally in the
tumour while minimising circulating levels
of the drug. It is anticipated that this
will lead to substantially increased sensitivity
of the tumour to the drug and to an ability
to reduce the dose of cyclophosphamide,
thereby reducing adverse side effects.
MetXia
has completed one Phase I/II trial in 12
late stage breast cancer and melanoma patients.
The product was found to be safe, well tolerated
and showed some clinical benefit. In addition
to local effects on tumour nodules that
had been treated with MetXia, there was
evidence of induction of systemic anti-tumour
immune responses. A second Phase I/II study,
using a higher potency version of MetXia
is close to completion. In the lower dose
group, data show that delivery of the therapeutic
gene to tumour cells is more than 10-fold
better than in the previous trial and also
that patients are mounting an anti-tumour
immune response, confirming the observations
made in the first trial. The product continues
to be safe, even at the higher potency.
|
| |
|
|
3. |
Gene Therapy Advisory Committee (GTAC)
The Gene Therapy Advisory Committee evaluates
gene therapy trial protocols on the basis
of the quality of the science, the details
of the clinical protocol and ethical considerations.
GTAC comprises technical experts and lay members.
Following
GTAC approval, clinical trial protocols
and the products used by them are then reviewed
by the Medicines and Healthcare products
Regulatory Agency (MHRA). On approval by
the MHRA, the products can be entered for
clinical trials.
|
| |
|
| For
further information please contact:
|
|
|
Oxford BioMedica plc
Professor Alan
Kingsman, Chief Executive
|
Tel: +44 (0)1865 783 000 |
| City/Financial
Enquiries
Mike
Wort/James Chandler
Beattie Financial |
Tel: +44 (0)20 7398 3300
|
| Scientific/Trade
Enquiries
Sue
Charles, Katja
Stout,
College Hill - Life Sciences |
Tel:
+44 (0)20 7321 3870 |
|
|
|
|
|
Top
of page
Website by College Hill - Life Sciences
|
| |
|
|
