Oxford Biomedica Announces Outcome of FDA Review And Updates On Trovax® Phase III Trist Study In Renal Cancer

Oxford Biomedica Announces Outcome of FDA Review And Updates On Trovax® Phase III Trist Study In Renal Cancer

Oxford, UK - 6 July 2009: Oxford BioMedica (LSE: OXB), a leading gene therapy company, today announces that it has received final comments from the US Food and Drug Administration (FDA) following the FDA's review of the Phase III TRIST study of TroVax in renal cancer and the Company's proposed clinical development outline. The FDA acknowledged all of the points raised by Oxford BioMedica and has provided a clear path for further development of TroVax in multiple cancer settings. TroVax is Oxford BioMedica's therapeutic cancer vaccine that targets the 5T4 tumour antigen.

Key highlights:

  • Latest analysis of the TRIST study further supports the anti-cancer activity of the 5T4-targeted immune response and shows a survival advantage to TroVax compared with the control arm in certain sub-sets of renal cancer patients
  • FDA supported the Company's proposal to pursue further development of TroVax in various metastatic cancer indications and invited submissions of adaptive Phase II/III trial designs in metastatic colorectal cancer
  • Oxford BioMedica is implementing a broad partnering initiative and expressions of interest have already been received
  • Discussions are ongoing with clinical trial networks and clinicians who may conduct independent studies of TroVax
  • Detailed results from next interim analysis, scheduled for July 2009, will be submitted for presentation at an oncology meeting in the autumn
  • The Phase III TRIST study is evaluating TroVax plus standard of care against placebo plus standard of care. The trial enrolled 733 patients with advanced or metastatic renal cancer that were classified as having a good or intermediate prognosis. Patients were randomised to one of three standards of care: interleukin-2, interferon-alpha or sunitinib. As previously reported, vaccinations were discontinued on 11 July 2008 based on the recommendation of the study's independent Data Safety Monitoring Board (DSMB), which concluded that the study would not meet its predefined primary endpoint of an improvement in overall survival.

The data evaluated by the DSMB were discussed with the FDA and it was agreed at a meeting on 3 October 2008 that plans to initiate further Phase III trials in colorectal cancer would be paused pending the FDA's review of additional data from the TRIST study. The subsequent documentation submitted and assessed by the FDA included: accurate and validated safety data up to a cut-off date of 11 August 2008 (30 days after the last administration of study medication); exploratory analyses and updated survival estimates (most recent analysis was up to 13 March 2009); and proposed clinical development outline for further trials of TroVax. The FDA has completed its review and has issued final comments following a further meeting with the Company on 3 June 2009.

As at 11 August 2008, there was a non-significant excess of 16 deaths in the TroVax arm compared with the control arm. However, at the most recent analysis to 13 March 2009, the survival curves of the two treatment arms have converged and there were 166 deaths in the TroVax arm compared with 168 deaths in the control arm. Median survival had not been reached in either group with 399 patients (54%) remaining on study.

Importantly, analysis of the data confirms prior clinical results, demonstrating that TroVax is both immunologically active and that there is a correlation between the strength of the 5T4-specific antibody response and improved survival. Exploratory analyses also suggest that a number of factors may have compromised the outcome of the study, including an imbalance with respect to patients' baseline prognostic factors and atypical results from a single clinical site.

In its comments, the FDA acknowledged that confounding factors may have contributed to the increased number of deaths in the TroVax arm at the August cut-off date. Furthermore, the FDA accepted that there was no evidence of specific adverse events that could attribute the imbalance of deaths to TroVax. The most frequent TroVax-related side effect was low-grade transient irritation at the injection site.

A prospectively agreed sub-set analysis of Intent to Treat (ITT) patients showed a significant advantage to TroVax in good prognosis patients receiving interleukin-2 (n= 50 in TroVax arm; and n= 50 in placebo arm) as at 13 March 2009. In addition, analyses suggest that abnormal baseline haematological parameters may have impacted on the ability of patients to mount effective immune responses to TroVax. Over 50% of patients in the TRIST study had ‘normal' baseline platelet, monocyte and haemoglobin levels (n= 372) and, in these patients, there was evidence of a survival benefit in favour of TroVax. These observations are potentially valuable for future studies of TroVax, enabling the selection of patients at screening that are more likely to respond and, hence, benefit from TroVax treatment.

The FDA noted that the analysis of patients receiving TroVax or placebo in combination with interleukin-2 was encouraging. Furthermore, the FDA agreed that, scientifically, it is reasonable to postulate that patients with a better haematological profile might respond more favourably to treatment with a cancer vaccine such as TroVax.

The FDA supported Oxford BioMedica's proposal to pursue clinical development of TroVax in metastatic disease, including colorectal, ovarian, hormone refractory prostate cancer, and triple-negative breast cancer, prior to further trials in renal cancer. In these indications, abnormal levels of platelets and other haematological parameters, which may affect the immune response, are less evident than in metastatic renal cancer. The FDA invited submissions of adaptive Phase II/III trial designs in metastatic colorectal cancer and will work with Oxford BioMedica and the Company's collaborators to prepare suitable protocols for submission and review. In addition, the FDA agreed to consider further development of TroVax in adjuvant indications, particularly adjuvant colorectal cancer, pending further clinical data in the metastatic setting.

Oxford BioMedica is committed to further development of TroVax with a partner and expressions of interest from prospective partners have already been received. Following the positive outcome of the FDA's review, the Company is implementing a broad partnering initiative and is also progressing discussions with clinical trial networks and clinicians who may conduct independent studies of TroVax.

The modified protocol of the TRIST study allows a detailed analysis of the data at six-month intervals, and the next interim analysis is scheduled for July 2009. The Company intends to present the results of this scheduled interim analysis at a forthcoming oncology meeting in the autumn.

Dr Stuart Naylor, Oxford BioMedica's Chief Scientific Officer, commented on the TRIST results and FDA guidance: "We are encouraged that the results of the TRIST study further support the anti-cancer activity of the 5T4-targeted immune response. Our exploratory analyses of this first placebo-controlled, randomised study of TroVax suggest that patients, who are more likely to respond to TroVax and benefit from treatment, can be pre-selected. Our constructive dialogue with the FDA provides a clear path for further development of TroVax in multiple cancer settings that have a high unmet need for novel safe and effective treatment options."

John Dawson, Oxford BioMedica's Chief Executive Officer, added: "The TRIST study has yielded valuable insights into the potential for TroVax as a therapeutic cancer vaccine, despite not achieving its primary endpoint. We are delighted by the outcome of the FDA's review, which enables us to advance our discussions with prospective partners and the oncology community. We have already received expressions of interest from several pharmaceutical companies that have previously reviewed the programme. We remain committed to the successful development and commercialisation of TroVax and we are now in a position to widen our partnering initiative such that we maximise the value of this key asset."

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Conference Call and Audio Web Cast on Monday, 6 July at 9.30am BST
Oxford BioMedica's management will host a conference call for analysts at 9.30am BST on Monday, 6 July 2009, to discuss the outcome of the FDA's review of the TRIST study. The dial-in details for analysts are available from Buchanan Communications (+44 (0) 20 7466 5000). Please click here to listen to the conference call replay.

Notes to editors

1. Oxford BioMedica plc
Oxford BioMedica (LSE: OXB) is a biopharmaceutical company developing innovative gene-based medicines and therapeutic vaccines that aim to improve the lives of patients with high unmet medical needs. The Company's technology platform includes a highly efficient gene delivery system (LentiVector®), which has specific advantages for targeting diseases of the central nervous system and the eye; and a unique tumour antigen (5T4), which is an ideal target for anti-cancer therapy. Through in-house and collaborative research, Oxford BioMedica has a broad pipeline. Partners include sanofi-aventis, Sigma-Aldrich and Wyeth. Technology licensees include Biogen-Idec, GlaxoSmithKline, Merck & Co and Pfizer. Further information is available at www.oxfordbiomedica.co.uk
2. TroVax®
TroVax is Oxford BioMedica's novel therapeutic cancer vaccine, which 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 Modified Vaccinia Ankara vector, 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 antigen.
3. Triple-Negative Breast Cancer
Triple-negative breast cancer refers to approximately 15% of breast carcinomas that do not express the oestrogen receptor, progesterone receptor and epidermal growth factor receptor type 2. This is a challenging disease to treat because of the absence of a specific target, but these tumours are potentially sensitive to immunotherapy.