Oxford BioMedica receives approval from GTAC for MetXia(R) to enter clinical trials in pancreatic cancer
Oxford, UK – 24 October 2003: 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-

Notes to Editors

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.

Further information is available at www.oxfordbiomedica.co.uk

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, +44 (0)1865 783 000

City/financial enquiries: Mike Wort/James Chandler, Beattie Financial, +44 (0)20 7398 3300

Scientific/trade press enquiries: Katja Stout/Sue Charles, Northbank Communications, +44 (0)20 7886 8150