Phase II results - TROVAX
Oxford Biomedica PLC
07 June 2006
For Immediate Release 7 JUNE 2006
OXFORD BIOMEDICA REPORTS NEW ENCOURAGING PHASE II RESULTS WITH TROVAX(R) AND
PROGRESS IN THE DEVELOPMENT PLAN
- Phase II Results at American Society of Clinical Oncology Annual Meeting -
Oxford, UK - 7 June 2006: Oxford BioMedica (LSE: OXB), a leading gene therapy
company, reported today that encouraging data from five Phase II studies of
TroVax, its lead cancer immunotherapy product, were presented at the Annual
Meeting of the American Society of Clinical Oncology (ASCO). In addition, the
Company provided an update on the clinical development plan for TroVax, which is
progressing towards the start of Phase III trials in renal and colorectal
cancer.
New Phase II results reported at ASCO:
• Updated analysis of unaudited tumour response data from two trials of
TroVax plus chemotherapy in metastatic colorectal cancer showed that 95% of
per protocol patients had disease control.
• Updated survival data from the two metastatic colorectal cancer trials
showed that a third of the patients were still alive with an average
follow-up time of more than two years.
• Data from Cancer Research UK's trial of TroVax adjuvant therapy in
colorectal cancer patients undergoing surgery for liver metastases showed
that 96% of patients produced an anti-tumour immune response and 56% of
operable patients remained disease-free after nine months of follow-up.
• First presentation of data from two studies of TroVax plus interleukin-2
in renal cell carcinoma showed that two of the first six evaluable patients
(33%) had partial responses. If reproduced in a larger study this would
compare favourably with a response rate of 10% for interleukin-2 alone.
Development plan update:
• QUASAR, a UK-based clinical trial network, has agreed to develop a Phase
III trial of TroVax in approximately 3,000 patients with early stage
colorectal cancer and the study will be submitted to the appropriate funding
agencies.
• Phase III TRIST study in renal cell carcinoma is on course to start in
the second half of 2006. Clinical Trial Applications are being filed in
European countries as part of the implementation of the protocol, for which
a Special Protocol Assessment was recently agreed with the FDA.
• Three further, small Phase II studies are starting in renal cell
carcinoma, evaluating TroVax in combination with interferon-a and sunitinib.
• Recruitment is proceeding rapidly in the recently announced Phase II
study of TroVax with GM-CSF in 24 patients with hormone refractory prostate
cancer. Eleven patients have already been recruited.
Commenting on the Phase II results and progress on the development plan, Oxford
BioMedica's Chief Medical Officer, Dr Mike McDonald, said: 'We are very pleased
that the positive results from the Phase II colorectal cancer trials continue to
be mirrored in renal cancer. There is growing interest in TroVax amongst the
clinical community in both Europe and the USA. This external support has enabled
us to broaden the clinical development of TroVax.'
On the approval by the QUASAR group of the proposed Phase III trial of TroVax,
the Chairman of QUASAR and Head of Clinical Pharmacology at the University of
Oxford, Professor David Kerr, said: 'The QUASAR group is committed to the Phase
III trial of TroVax in early stage colorectal cancer. We must now secure the
necessary grant funding to start this important trial and potentially provide a
novel therapy for this large patient group where treatment options have evolved
little in recent years.'
Oxford BioMedica's Chief Executive Officer, Professor Alan Kingsman added:
'These new clinical results further illustrate the potential for TroVax to treat
different cancers at different stages of disease and support our strategy of
advancing to larger and pivotal registration trials. We look forward to starting
our Phase III TRIST trial of TroVax in renal cancer later this year and working
with both QUASAR and commercial partners on the design and initiation of
additional trials in colorectal cancer.'
Phase II results of TroVax plus chemotherapy in colorectal cancer
Oxford BioMedica has completed two Phase II trials of TroVax in first-line
treatment of metastatic colorectal cancer alongside two standard of care
chemotherapy regimens: irinotecan, 5-fluorouracil and leucovorin (IFL) and
oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX). The two single-arm,
open-label trials enrolled a total of 36 patients. On 6 June 2006 at the ASCO
meeting, the Company presented final safety and immunology data including new
details of the cytotoxic T-cell response, efficacy results including an update
on both tumour responses and survival, and also analysis of the relationship
between the magnitude of immune responses and clinical benefit.
As reported previously, the primary endpoints of safety and anti-tumour
immunological responses were achieved and the results confirmed the excellent
safety profile of TroVax with no serious adverse events being attributed to the
product. All 23 per protocol patients (>3 TroVax immunisations and >6
chemotherapy cycles) across the two trials mounted an anti-tumour immune
response. Immune responses were higher than in the Phase I/II study and
cytotoxic T-lymphocyte (CD8+) levels were exceptionally high, reaching
frequencies of 1 per 1000 peripheral blood mononuclear cells. Such high levels
are normally only seen in infectious diseases where the CD8+ response frequently
clears the infection.
Clinical benefit exceeded the Company's expectation based on previously reported
data for chemotherapy alone. Based on updated, unaudited computerised tomography
(CT) scans, 95% of per protocol patients showed disease control, which is higher
than the previously reported figure of 91%: 17% had complete responses; 43% had
partial responses; and 35% had stable disease. In the TroVax plus FOLFOX trial,
there was a statistically significant (p <0.02) correlation between patients'
5T4-specific immune response and their tumour response.
The Company also presented updated survival information for the two studies.
However, it should be noted that patient numbers are too small to provide a
rigorous conclusion and comparisons with historical data can be unreliable. In
the modified intent to treat group (>2 TroVax immunisations) of 30 patients,
TroVax extended median survival from 72 weeks to 80 weeks and improved survival
at twelve months from 70% to 90%. Importantly, as at 10 May 2006, ten of the 30
patients remained alive with an average follow-up time of more than two years.
The Company regards these data as encouraging and believe that, if these
observations were reproduced in a pivotal study, they would be sufficient to
support product registration.
Phase II results of TroVax adjuvant therapy in colorectal cancer:
Clinicians from the Christie Hospital and Paterson Institute for Cancer
Research, both of Manchester, UK, have completed enrolment of a Phase II trial
of TroVax in colorectal cancer patients who have operable liver metastases. The
single-arm, open-label trial, which enrolled 20 patients, is sponsored by Cancer
Research UK. Patients received TroVax immunisations before surgery (neoadjuvant)
and after surgery (adjuvant). On 4 June 2006 at the ASCO meeting, the Principal
Investigators for the trial presented safety and immunological data, and
clinical outcomes from patient follow-up.
The primary objective of the trial was to investigate the immunological
responses to TroVax during potentially curative surgery for colorectal cancer
liver metastases. The group of patients selected for the trial had good
performance status, but patients often have micro-metastatic disease that
persists post-operatively. TroVax could provide a safe and effective treatment
option for these patients that have a low but metastatic tumour burden.
TroVax was well tolerated in all patients with no serious adverse events
associated with the product. Of the 20 patients recruited, 16 had successful
surgical resection of their colorectal cancer liver metastases. All evaluable
resected tumours were positive for the 5T4 antigen, the target for TroVax.
The primary endpoint of immunological response was achieved. In the intent to
treat population, 19 of the 20 patients (95%) mounted anti-tumour immune
responses against 5T4. Four patients were withdrawn for incorrect diagnosis or
inoperable cancer. Clinical analysis was conducted on the remaining 16 evaluable
patients. At a median follow-up of 9.1 months, nine of these 16 patients (56%)
remained disease-free. Oxford BioMedica is encouraged by the data to date from
Cancer Research UK's trial of TroVax in this setting of adjuvant therapy to
surgery for liver metastases.
Preliminary Phase II results of TroVax plus interleukin-2 (IL-2) in renal cell
carcinoma
Two Phase II trials of TroVax with either high dose or low dose IL-2 are ongoing
in the USA. The trials are designed to gather information on the safety of the
combination treatments as well as on immune responses to the 5T4 tumour antigen.
Results from the two trials were published in the ASCO Proceedings for the
Annual Meeting.
To date, 27 of 50 patients have been recruited into the two trials. There have
been no serious adverse events related to TroVax, which is consistent with the
excellent safety profile of the product across all trials, and TroVax treatment
was well tolerated. Across both trials, 15 of 17 evaluable (>3 TroVax
immunisations) patients (88%) have shown anti-tumour antibody responses to 5T4.
The antibody levels were at the top end of the range reported from the Phase II
trials with TroVax in patients with colorectal cancer undergoing chemotherapy.
Analysis of cytotoxic T-lymphocyte responses is in progress.
To date, unaudited CT scans are available for the first six patients. Of these,
two (33%) have shown partial responses based on industry-standard criteria known
as Response Evaluation Criteria in Solid Tumours (RECIST). According to the
literature, IL-2 is usually associated with a clinical response rate of only 10%
in this patient group.
The Company and the Principal Investigators for these trials are encouraged by
the frequency of clinical responses with TroVax, albeit in a small number of
patients at this stage. These data endorse the Company's strategy to initiate
the Phase III TRIST trial, which includes TroVax alongside low dose IL-2.
Development plan update:
(i) Renal cell carcinoma (RCC)
The Company is expanding its Phase II programme in RCC with three additional
single-arm, open-label Phase II studies to assess TroVax in combination with
either interferon-alpha (IFNa) or sunitinib (Sutent(R)). These small trials are
designed to broaden the clinical experience with TroVax and provide further
support for the planned Phase III TRIST trial that will use IFN-a and Sutent(R),
in addition to IL-2, as standard of care treatments. Enrolment has commenced in
the first of these studies, which are being conducted in centres in the UK and
the USA.
The Company's multi-centre, randomised, double-blind, placebo-controlled
700-patient Phase III trial, TRIST (TroVax Renal Immunotherapy Survival Trial),
is on-track to commence recruitment in the second half of 2006. The manufacture
of the trial material is largely complete. Oxford BioMedica secured an agreement
with the US Food and Drug Administration (FDA) on a Special Protocol Assessment
in May 2006 and Clinical Trial Applications are in the process of being filed
with the relevant European agencies. The trial is designed for rapid patient
recruitment and has a primary endpoint of overall survival. The duration of the
trial will be determined by the number of deaths in the study group. Median
survival for this patient group is approximately 11 months. The trial protocol
includes the appointment of a Safety and Efficacy Monitoring Board that will
periodically review the data and make recommendations based on the safety and
efficacy of the different treatment arms. TRIST is expected to reach a
conclusion in 2008-09 and could support product registration in 2009.
(ii) Colorectal cancer
Oxford BioMedica has advanced its discussions with the QUASAR group, which is a
UK-based clinical trial network, which has been funded from a variety of sources
including the UK Medical Research Council and Department of Health. In November
2005, the Company reported that QUASAR had expressed interest in conducting a
Phase III trial of TroVax in early stage (Stage II/III) colorectal cancer
patients but that further evaluation was required. QUASAR has completed its
evaluation, confirmed its commitment and will seek funding for the proposed
trial through the appropriate agencies.
The proposed design is a randomised trial in about 3,000 patients. TroVax would
be used during or after adjuvant chemotherapy with a primary endpoint of
disease-free survival at three years. The study is likely to be configured to
enable product registration in Europe and the USA. The QUASAR group has
successfully conducted other large studies of adjuvant therapy in this disease
setting. These previous QUASAR trials have enrolled about 7,000 patients over
the last seven years.
Separately, the Company is planning a randomised trial in first-line treatment
of metastatic (Stage IV) colorectal cancer. The preliminary trial design is to
evaluate TroVax alongside standard of care treatment. It could be configured as
a Phase IIb or Phase III trial. The final design of this trial depends on the
outcome of licensing discussions, since the Company expects this trial to be
funded and conducted by a commercial partner.
(iii) Prostate cancer
Oxford BioMedica reported on 23 May 2006 that a Phase II trial of TroVax in
patients with prostate cancer had started. The trial, which is supported by the
Methodist Hospital in Houston, is designed to enrol 24 men with
hormone-refractory prostate cancer who have previously received chemotherapy or
have refused chemotherapy and have progressive disease. The open-label trial has
two arms (12 patients each) to assess the activity of TroVax alone versus TroVax
alongside an approved treatment for prostate cancer, granulocyte
macrophage-colony stimulating factor (GM-CSF). The primary objectives of the
trial are to evaluate the safety and synergies of the combination treatment.
Eleven patients have been enrolled into the trial to date.
-Ends-
For further information, please contact:
Oxford BioMedica plc: Tel: +44 (0)1865 783 000
Professor Alan Kingsman, Chief Executive
City/Financial Enquiries: Tel: +44 (0)20 7466 5000
Lisa Baderoon/ Mark Court/ Mary-Jane Johnson Buchanan
Communications
Scientific/Trade Press Enquiries: Tel: +44 (0)20 7886 8150
Katja Stout/ Susan Yu
Northbank Communications
Notes to editors
1. Oxford BioMedica
Oxford BioMedica (LSE: OXB) is a biopharmaceutical company specialising in the
development of novel gene-based therapeutics with a focus on oncology and
neurotherapy. The Company was established in 1995 as a spin out from Oxford
University, and is listed on the London Stock Exchange.
Oxford BioMedica has core expertise in gene delivery, as well as in-house
clinical, regulatory and manufacturing know-how. In oncology, the pipeline
includes two candidates in multiple Phase II trials, and a preclinical targeted
antibody therapy in collaboration with Wyeth. A Phase III trial in renal cancer
with TroVax, the lead cancer immunotherapy candidate, is expected to start in
the second half of 2006. In neurotherapy, the Company's lead product is a gene
therapy for Parkinson's disease, which is expected to enter clinical development
in 2006, and four further preclinical candidates. The Company is underpinned by
over 80 patent families, which represent one of the broadest patent estates in
the field.
The Company has a staff of approximately 70 split between its main facilities in
Oxford and its wholly owned subsidiary, BioMedica Inc, in San Diego, California.
Oxford BioMedica has corporate collaborations with Wyeth, Intervet,
Sigma-Aldrich, Viragen, MolMed, VIRxSYS and Kiadis; and has licensed technology
to a number of companies including Merck & Co, Biogen Idec and Pfizer.
Further information is available at www.oxfordbiomedica.co.uk
2. TroVax(R)
TroVax is Oxford BioMedica's leading cancer immunotherapy product. It is
designed specifically to stimulate an anti-cancer immune response and has
potential application in most solid tumour types. TroVax targets the tumour
antigen 5T4, which is broadly distributed throughout a wide range of solid
tumours. The presence of 5T4 is correlated with poor prognosis. The product
consists of a poxvirus (MVA) gene transfer system, which delivers the gene for
5T4 and stimulates a patient's body to produce an anti-5T4 immune response. This
immune response destroys tumour cells carrying the 5T4. TroVax has attracted
external support from Cancer Research UK and the US National Cancer Institute.
Over 100 patients have now been treated with TroVax in eight clinical trials
(collectively over 400 doses). The Company is targeting colorectal cancer and
renal cell carcinoma (RCC) as lead indications for the development of TroVax.
Renal cell carcinoma is an indication where TroVax might achieve a rapid route
to product registration. A clinical trial in prostate cancer is also underway
and a trial in breast cancer is planned.
This information is provided by RNS
The company news service from the London Stock Exchange
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