7th Jun 2006 07:00
Oxford Biomedica PLC07 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 therapycompany, reported today that encouraging data from five Phase II studies ofTroVax, its lead cancer immunotherapy product, were presented at the AnnualMeeting of the American Society of Clinical Oncology (ASCO). In addition, theCompany provided an update on the clinical development plan for TroVax, which isprogressing towards the start of Phase III trials in renal and colorectalcancer. 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, OxfordBioMedica's Chief Medical Officer, Dr Mike McDonald, said: "We are very pleasedthat the positive results from the Phase II colorectal cancer trials continue tobe mirrored in renal cancer. There is growing interest in TroVax amongst theclinical community in both Europe and the USA. This external support has enabledus 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 ofOxford, Professor David Kerr, said: "The QUASAR group is committed to the PhaseIII trial of TroVax in early stage colorectal cancer. We must now secure thenecessary grant funding to start this important trial and potentially provide anovel therapy for this large patient group where treatment options have evolvedlittle in recent years." Oxford BioMedica's Chief Executive Officer, Professor Alan Kingsman added:"These new clinical results further illustrate the potential for TroVax to treatdifferent cancers at different stages of disease and support our strategy ofadvancing to larger and pivotal registration trials. We look forward to startingour Phase III TRIST trial of TroVax in renal cancer later this year and workingwith both QUASAR and commercial partners on the design and initiation ofadditional 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-linetreatment of metastatic colorectal cancer alongside two standard of carechemotherapy regimens: irinotecan, 5-fluorouracil and leucovorin (IFL) andoxaliplatin, 5-fluorouracil and leucovorin (FOLFOX). The two single-arm,open-label trials enrolled a total of 36 patients. On 6 June 2006 at the ASCOmeeting, the Company presented final safety and immunology data including newdetails of the cytotoxic T-cell response, efficacy results including an updateon both tumour responses and survival, and also analysis of the relationshipbetween the magnitude of immune responses and clinical benefit. As reported previously, the primary endpoints of safety and anti-tumourimmunological responses were achieved and the results confirmed the excellentsafety profile of TroVax with no serious adverse events being attributed to theproduct. All 23 per protocol patients (>3 TroVax immunisations and >6chemotherapy cycles) across the two trials mounted an anti-tumour immuneresponse. Immune responses were higher than in the Phase I/II study andcytotoxic T-lymphocyte (CD8+) levels were exceptionally high, reachingfrequencies of 1 per 1000 peripheral blood mononuclear cells. Such high levelsare normally only seen in infectious diseases where the CD8+ response frequentlyclears the infection. Clinical benefit exceeded the Company's expectation based on previously reporteddata for chemotherapy alone. Based on updated, unaudited computerised tomography(CT) scans, 95% of per protocol patients showed disease control, which is higherthan the previously reported figure of 91%: 17% had complete responses; 43% hadpartial responses; and 35% had stable disease. In the TroVax plus FOLFOX trial,there was a statistically significant (p 2 TroVax immunisations) of 30 patients,TroVax extended median survival from 72 weeks to 80 weeks and improved survivalat twelve months from 70% to 90%. Importantly, as at 10 May 2006, ten of the 30patients remained alive with an average follow-up time of more than two years.The Company regards these data as encouraging and believe that, if theseobservations were reproduced in a pivotal study, they would be sufficient tosupport product registration. Phase II results of TroVax adjuvant therapy in colorectal cancer: Clinicians from the Christie Hospital and Paterson Institute for CancerResearch, both of Manchester, UK, have completed enrolment of a Phase II trialof TroVax in colorectal cancer patients who have operable liver metastases. Thesingle-arm, open-label trial, which enrolled 20 patients, is sponsored by CancerResearch UK. Patients received TroVax immunisations before surgery (neoadjuvant)and after surgery (adjuvant). On 4 June 2006 at the ASCO meeting, the PrincipalInvestigators for the trial presented safety and immunological data, andclinical outcomes from patient follow-up. The primary objective of the trial was to investigate the immunologicalresponses to TroVax during potentially curative surgery for colorectal cancerliver metastases. The group of patients selected for the trial had goodperformance status, but patients often have micro-metastatic disease thatpersists post-operatively. TroVax could provide a safe and effective treatmentoption for these patients that have a low but metastatic tumour burden. TroVax was well tolerated in all patients with no serious adverse eventsassociated with the product. Of the 20 patients recruited, 16 had successfulsurgical resection of their colorectal cancer liver metastases. All evaluableresected tumours were positive for the 5T4 antigen, the target for TroVax. The primary endpoint of immunological response was achieved. In the intent totreat population, 19 of the 20 patients (95%) mounted anti-tumour immuneresponses against 5T4. Four patients were withdrawn for incorrect diagnosis orinoperable cancer. Clinical analysis was conducted on the remaining 16 evaluablepatients. 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 fromCancer Research UK's trial of TroVax in this setting of adjuvant therapy tosurgery for liver metastases. Preliminary Phase II results of TroVax plus interleukin-2 (IL-2) in renal cellcarcinoma Two Phase II trials of TroVax with either high dose or low dose IL-2 are ongoingin the USA. The trials are designed to gather information on the safety of thecombination treatments as well as on immune responses to the 5T4 tumour antigen.Results from the two trials were published in the ASCO Proceedings for theAnnual Meeting. To date, 27 of 50 patients have been recruited into the two trials. There havebeen no serious adverse events related to TroVax, which is consistent with theexcellent safety profile of the product across all trials, and TroVax treatmentwas well tolerated. Across both trials, 15 of 17 evaluable (>3 TroVaximmunisations) 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 IItrials 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 knownas Response Evaluation Criteria in Solid Tumours (RECIST). According to theliterature, 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 bythe frequency of clinical responses with TroVax, albeit in a small number ofpatients at this stage. These data endorse the Company's strategy to initiatethe 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 additionalsingle-arm, open-label Phase II studies to assess TroVax in combination witheither interferon-alpha (IFNa) or sunitinib (Sutent(R)). These small trials aredesigned to broaden the clinical experience with TroVax and provide furthersupport 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 inthe first of these studies, which are being conducted in centres in the UK andthe USA. The Company's multi-centre, randomised, double-blind, placebo-controlled700-patient Phase III trial, TRIST (TroVax Renal Immunotherapy Survival Trial),is on-track to commence recruitment in the second half of 2006. The manufactureof the trial material is largely complete. Oxford BioMedica secured an agreementwith the US Food and Drug Administration (FDA) on a Special Protocol Assessmentin May 2006 and Clinical Trial Applications are in the process of being filedwith the relevant European agencies. The trial is designed for rapid patientrecruitment and has a primary endpoint of overall survival. The duration of thetrial will be determined by the number of deaths in the study group. Mediansurvival for this patient group is approximately 11 months. The trial protocolincludes the appointment of a Safety and Efficacy Monitoring Board that willperiodically review the data and make recommendations based on the safety andefficacy of the different treatment arms. TRIST is expected to reach aconclusion 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 aUK-based clinical trial network, which has been funded from a variety of sourcesincluding the UK Medical Research Council and Department of Health. In November2005, the Company reported that QUASAR had expressed interest in conducting aPhase III trial of TroVax in early stage (Stage II/III) colorectal cancerpatients but that further evaluation was required. QUASAR has completed itsevaluation, confirmed its commitment and will seek funding for the proposedtrial through the appropriate agencies. The proposed design is a randomised trial in about 3,000 patients. TroVax wouldbe used during or after adjuvant chemotherapy with a primary endpoint ofdisease-free survival at three years. The study is likely to be configured toenable product registration in Europe and the USA. The QUASAR group hassuccessfully conducted other large studies of adjuvant therapy in this diseasesetting. These previous QUASAR trials have enrolled about 7,000 patients overthe last seven years. Separately, the Company is planning a randomised trial in first-line treatmentof metastatic (Stage IV) colorectal cancer. The preliminary trial design is toevaluate TroVax alongside standard of care treatment. It could be configured asa Phase IIb or Phase III trial. The final design of this trial depends on theoutcome of licensing discussions, since the Company expects this trial to befunded and conducted by a commercial partner. (iii) Prostate cancer Oxford BioMedica reported on 23 May 2006 that a Phase II trial of TroVax inpatients with prostate cancer had started. The trial, which is supported by theMethodist Hospital in Houston, is designed to enrol 24 men withhormone-refractory prostate cancer who have previously received chemotherapy orhave refused chemotherapy and have progressive disease. The open-label trial hastwo arms (12 patients each) to assess the activity of TroVax alone versus TroVaxalongside an approved treatment for prostate cancer, granulocytemacrophage-colony stimulating factor (GM-CSF). The primary objectives of thetrial 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 ExecutiveCity/Financial Enquiries: Tel: +44 (0)20 7466 5000 Lisa Baderoon/ Mark Court/ Mary-Jane Johnson BuchananCommunicationsScientific/Trade Press Enquiries: Tel: +44 (0)20 7886 8150 Katja Stout/ Susan YuNorthbank Communications Notes to editors 1. Oxford BioMedica Oxford BioMedica (LSE: OXB) is a biopharmaceutical company specialising in thedevelopment of novel gene-based therapeutics with a focus on oncology andneurotherapy. The Company was established in 1995 as a spin out from OxfordUniversity, and is listed on the London Stock Exchange. Oxford BioMedica has core expertise in gene delivery, as well as in-houseclinical, regulatory and manufacturing know-how. In oncology, the pipelineincludes two candidates in multiple Phase II trials, and a preclinical targetedantibody therapy in collaboration with Wyeth. A Phase III trial in renal cancerwith TroVax, the lead cancer immunotherapy candidate, is expected to start inthe second half of 2006. In neurotherapy, the Company's lead product is a genetherapy for Parkinson's disease, which is expected to enter clinical developmentin 2006, and four further preclinical candidates. The Company is underpinned byover 80 patent families, which represent one of the broadest patent estates inthe field. The Company has a staff of approximately 70 split between its main facilities inOxford 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 technologyto 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 isdesigned specifically to stimulate an anti-cancer immune response and haspotential application in most solid tumour types. TroVax targets the tumourantigen 5T4, which is broadly distributed throughout a wide range of solidtumours. The presence of 5T4 is correlated with poor prognosis. The productconsists of a poxvirus (MVA) gene transfer system, which delivers the gene for5T4 and stimulates a patient's body to produce an anti-5T4 immune response. Thisimmune response destroys tumour cells carrying the 5T4. TroVax has attractedexternal 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 andrenal cell carcinoma (RCC) as lead indications for the development of TroVax.Renal cell carcinoma is an indication where TroVax might achieve a rapid routeto product registration. A clinical trial in prostate cancer is also underwayand a trial in breast cancer is planned. This information is provided by RNS The company news service from the London Stock ExchangeRelated Shares:
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