Oxford
BioMedica Oncology Update
Oxford
BioMedica announced today an update on recent R&D and corporate development
progress within its oncology portfolio.
Highlights:
- Encouraging initial TroVax® Phase II results in colorectal
cancer
- Company's first IND submission for TroVax in renal
cancer
- Cancer Research UK makes regulatory submission to GTAC
for TroVax Phase II trial
- Commercial-scale manufacturing agreement for TroVax
- Wyeth collaboration on anti-tumour antibody meets key milestone
- Intervet research collaboration on TroVax-VET for cancer
in companion animals extended to full option to license
agreement
- Positive final results from the second MetXia® Phase
I/II trial in breast cancer
- MHRA approval for the MetXia Phase I/II trial in pancreatic
cancer
TROVAX:
ENCOURAGING INITIAL PHASE II RESULTS IN COLORECTAL CANCER
The
Company is reporting initial data from the Phase II study
of TroVax in patients with Stage IV (Dukes' D) colorectal
cancer who are receiving first line chemotherapy of 5-fluorouracil
(5-FU) and irinotecan. A total of nine patients have been
recruited to date. Three of these have been withdrawn from
the trial because of an inability to withstand the chemotherapy.
The remaining six patients are partway through their TroVax
immunisation regime and have shown no adverse effects that
can be attributed to TroVax.
Although
these patients have not completed their course of immunisations,
the Company is encouraged by the fact that
anti-tumour immune responses have been mounted. Further
immunisations are expected to increase this response. Furthermore,
T-cell
(CD4 and CD8) counts, which are indicators of immune competence,
have not been significantly diminished by the chemotherapy;
supporting the notion that immunotherapy alongside chemotherapy
may be a feasible strategy.
Recruitment
should be complete by Q1 2004 and further data will be
reported with the Company's full year results.
Recruitment for the second Phase II study, in Stage IV colorectal
cancer patients receiving the chemotherapy combination of
5-FU and oxaliplatin, is underway and initial data will be
available in Q2 2004.
TROVAX:
FIRST IND SUBMISSION FOR PHASE II TRIAL IN RENAL CANCER
The
Company submitted its first IND application to the US FDA
on 3 December 2003. The application is for a Phase II
trial of TroVax in patients with metastatic renal cancer.
There are about 30,000 cases of metastatic renal cancer
in the US. Currently the standard of care in many US hospitals,
after resection of the primary tumour, is IL2 and this
has
been shown to have some benefit. Given that IL2 is known
to enhance immune responses, this suggests that the tumours
may be responsive to immunological strategies. The rationale
for this trial is that the immune response produced by
TroVax may halt or delay the progression of metastases
so increasing
survival beyond the current median of 13 months.
There
is a great need for additional therapies for renal cancer
and the regulatory strategy will involve seeking fast
track approval and opening discussions about product registration
if early data are compelling. The endpoints will be immune
responses, tumour responses, time to disease progression
and survival. The renal cancer trial will involve 30 patients
initially and will be run at the Columbia Hospital, NY
although additional NCI groups may be included in the future
to increase
the rate of patient recruitment. This trial has already
been approved by the US Recombinant Advisory Committee
(RAC) and
has been the subject of a successful pre-IND meeting with
the FDA. A response from the FDA is expected in early January.
TROVAX:
CANCER RESEARCH UK MAKES REGULATORY SUBMISSION FOR PHASE
II TRIAL
Cancer
Research UK has submitted the trial protocol for a Phase
II trial with TroVax in colorectal cancer to the UK
Gene Therapy Advisory Committee and a response is expected
by 22 December 2003. Oxford BioMedica announced, in August
2003, that Cancer Research UK had agreed to conduct and
sponsor an open label Phase II trial with TroVax, in colorectal
cancer
patients who have liver metastases. The decision by Cancer
Research UK followed extensive review of the successful
Phase I/II data of TroVax in colorectal cancer patients.
The
patient population in the trial will comprise twenty Stage
IV colorectal cancer patients who are to undergo surgery
for resectable liver metastases. Patients will receive
injections
of TroVax followed by surgery approximately two weeks later.
Biopsies of the tumour will be taken at surgery and analysed
for TroVax stimulated immune activity. Further vaccinations
will be given after surgery. Patients' management will
then continue as standard, usually including adjuvant chemotherapy.
Patients will be followed after the final vaccination to
assess immune responses and toxicity and then monitored over
the longer term for clinical benefit.
TROVAX:
COMMERCIAL-SCALE MANUFACTURING SECURED FOR LARGER TRIALS
In September
2003, Oxford BioMedica signed a manufacturing agreement
for the supply of more than 10,000 doses of GMP
grade TroVax to cover the requirements for large randomised
trials. The manufacturing process is based on the same
technology commonly used for infectious disease vaccines.
Since unit
dose costs can be kept to a minimum, the process is ideal
for the commercial production of TroVax.
WYETH
COLLABORATION: MILESTONE ACHIEVED WITH ANTI-TUMOUR ANTIBODY
CONJUGATE
Wyeth
has completed key preclinical studies with Oxford BioMedica's
anti-tumour monoclonal antibody linked to calicheamicin,
a potent cytotoxic agent. These results trigger a further
milestone payment to Oxford BioMedica before the end
of 2003.
The
agreement with Wyeth was originally signed in January 2001.
Earlier this year, Wyeth exercised its option for an
exclusive license to Oxford BioMedica's anti-tumour
antibody for all human cancer indications. Wyeth has full
responsibility for the costs of development, marketing and
manufacture of products that arise from the programme. The
potential value of the deal for Oxford BioMedica is $24 million
in upfront and milestone payments. Additionally, Oxford BioMedica
will receive royalties on product sales by Wyeth.
The
successful preclinical work undertaken by Wyeth included
optimising the antibody and calicheamicin conjugate and
conducting proof-of-efficacy studies in relevant tumour
models. Timelines
for the completion of preclinical development and initial
clinical trials will be established in early 2004
INTERVET
COLLABORATION: EXTENSION OF DEAL ON TROVAX-VET
On
15 December 2003 an option to license agreement was signed
with Intervet (a division of Akzo Nobel) confirming the
ongoing commitment of Intervet to the development of novel
animal
cancer vaccines based on Oxford BioMedica's technology.
In January 2003, Oxford BioMedica announced the signing of
a research agreement with Intervet for the development of
TroVax-VET. As reported in January, the Company and Intervet
entered negotiations for a full option to license agreement
for TroVax-VET and a number of other veterinary cancer products
arising from Oxford BioMedica's antigen discovery
programme.
METXIA:
FINAL RESULTS FROM SECOND PHASE I/II TRIAL IN BREAST CANCER
Recruitment
is now complete in the second Phase I/II trial with MetXia,
mainly in breast cancer patients. Recruitment
was halted at eight patients because all the requirements
of the trial have been met, although patients will continue
to be monitored. This second Phase I/II trial is using
an improved version of MetXia that effectively increases
the
dose level. One of the goals of the trial is to show that
this higher potency form of MetXia is safe. The trial is
also designed to confirm the encouraging immune responses
observed in an earlier clinical trial of the original formulation
of MetXia as well as to determine whether the higher potency
version of the product delivers the therapeutic gene to
tumours more efficiently in humans, as it does in preclinical
models.
In line
with initial results reported in July 2003 for the low
dose group with the improved formulation, the high dose
patients have shown enhanced gene transfer in all cases
with
no adverse effects of the treatment. Furthermore, five
out of seven patients assessed so far have shown an increased
immune response to known tumour molecules, confirming the
immunogenic properties of MetXia. Detailed data will be
published
next year in peer-reviewed journals and at relevant conferences.
METXIA:
MHRA APPROVAL FOR START OF A PHASE I/II TRIAL IN PANCREATIC
CANCER
On 11
December 2003, the Company received approval from the UK
MHRA to proceed with a Phase I/II study of MetXia 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.
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 Oxford BioMedica's oncology programmes,
Dr. Susan Kingsman, SVP Research & Development, said "Overall
we are pleased with the progress of TroVax and MetXia.
Although patient recruitment has been rather slow in some
cases, the
clinical data are encouraging. We are delighted to be initiating
clinical trial programmes in the USA and we expect patient
recruitment rates to be substantially faster in that environment.
We are also particularly pleased to see the Wyeth programme
going so well".
In regard
to Oxford BioMedica's business development
activities in oncology, Nick Woolf, SVP Corporate Strategy,
said "We are very encouraged by the strong support
from our current partners. Furthermore, we have received
high levels of interest in our in-house pipeline, particularly
TroVax, and a key priority for Oxford BioMedica is to secure
new collaborations for our lead programmes in 2004."
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