Oxford Biomedica Regulatory News (OXB)

2 Mar 2005 07:01

Oxford Biomedica PLC02 March 2005 FOR IMMEDIATE RELEASE 2 MARCH 2005 OXFORD BIOMEDICA ANNOUNCES ENCOURAGING RESULTS FROM THREE PHASE II TRIALS OF TROVAX IN PATIENTS WITH COLORECTAL CANCER Oxford, UK - 2 March 2005: Oxford BioMedica (LSE: OXB), the leading gene therapycompany, today announces encouraging results from three ongoing Phase II trialsof TroVax, its lead cancer immunotherapy, in the treatment of metastaticcolorectal cancer. Highlights of the Phase II trial results: • In two trials in the first line setting in combination with chemotherapy: o 25 patients are evaluable for immunological responses o 19 patients are evaluable for tumour responses (tumour stabilisation and tumour shrinkage) o The primary endpoints of safety and immunological responses have been achieved o The secondary endpoint of clinical benefit has exceeded expectation o The immune response rate was exceptionally high. All 25 patients mounted immune responses to the 5T4 tumour antigen o The tumour response rate was better than expected. Eighteen of 19 patients responded to treatment (three complete responses, ten partial responses and five disease stabilisations) o Chemotherapy did not affect the frequency of immune responses compared to the Phase I/II trials in second line treatment • In Cancer Research UK's trial in the (neo) adjuvant to surgery setting, all eight evaluable patients mounted immune responses • In all three trials, TroVax has an excellent safety profile to date. No serious adverse events were attributed to the product New data from two trials in first line treatment of metastatic colorectal cancerwith concomitant chemotherapy have confirmed previous indications that theprimary endpoints of safety and immunological responses have been achieved. Allpatients that have reached the interim stage of the trial have shown an immuneresponse to the 5T4 tumour antigen. Today, the Company is also reporting that, in the two trials, the secondaryendpoint of clinical benefit has exceeded expectation. Eighteen of 19 evaluablepatients responded to treatment. Whilst five patients had disease stabilisationfollowing treatment, 13 of the 19 patients were defined as clinical respondersaccording to industry standard criteria. These comprised three complete (totaltumour shrinkage) responders and ten partial (more than 30 per cent tumourshrinkage) responders. In addition, analysis of the first evaluable patients in a third Phase II trialof TroVax in colorectal cancer patients undergoing surgery for liver metastaseshas shown that all patients have mounted an immune response against the targettumour antigen. This investigator initiated trial is sponsored by CancerResearch UK. The results from the earlier Phase I/II studies showed a highly significantcorrelation between patients' immune response to TroVax and time to diseaseprogression, which translated into a correlation with improved overall survival.Data emerging from the Phase II trials suggest that the magnitude and durationof immune responses may be even greater in first line treatment with concomitantchemotherapy and in the (neo) adjuvant setting with surgery. The new datareported today provide further evidence that TroVax may offer potential benefitto patients with colorectal cancer. Commenting on the Phase II results with TroVax in colorectal cancer, ProfessorAlan Kingsman, Chief Executive of Oxford BioMedica, said: "We are very pleasedwith the progress of these three Phase II trials of TroVax in colorectal cancer.The high frequency of anti-5T4 responses in patients confirms the immunologicaleffectiveness of TroVax and the preliminary clinical response data lookpromising. Based on current data, we are optimistic that TroVax will have a roleto play in the treatment of cancer and we look forward to testing this inpivotal clinical studies." Commenting on Cancer Research UK's initial Phase II results with TroVax in theadjuvant setting, Dr. Sally Burtles, Director of Drug Development of CancerResearch UK said: "We are delighted that the vaccine has stimulated an immuneresponse to 5T4 in all of the evaluable patients to date. Further trials will beneeded to find out if this translates into clinical benefit for patients." Phase II trials of TroVax plus chemotherapy in first line treatment Oxford BioMedica initiated two open label Phase II trials in first linetreatment of metastatic colorectal cancer in 2003. The two trials were designedto investigate whether concomitant chemotherapy affected patients' immuneresponses to TroVax. Enrolment in both trials (TroVax plus IFL and TroVax plusFOLFOX) was completed in September 2004. The recruitment objective was to haveten evaluable patients in each trial. The primary endpoints were safety anddemonstrable immune responses to the 5T4 tumour antigen. On 1 September 2004, the Company reported that the primary endpoints were likelyto be achieved based on preliminary data from 13 patients who had reached theinterim analysis point, defined as four TroVax immunisations and more than eightcycles of chemotherapy. Of these patients, 11 (85 per cent) had mounted antibodyand/or cellular anti-5T4 immune responses. These encouraging results have been confirmed as the trials have progressed. Todate, 25 patients have been assessed at the interim stage of the trial. Therehave been no serious adverse events attributed to TroVax treatment and thenumber of patients mounting an immune response has risen to 100 per cent withall 25 patients showing antibody and/or cellular responses to the tumourantigen. Furthermore, 19 patients have been assessed for tumour responses (tumourstabilisation and tumour shrinkage), having received at least three TroVaximmunisations and one or more computed tomography scans. Patients entered thetrial with progressive disease, and 18 of 19 patients had a tumour responsefollowing treatment. Thirteen of 19 patients were classified as clinicalresponders, comprising three complete and ten partial responses. Two independent studies of the chemotherapy regimens alone reported clinicalresponse rates in evaluable patients of 41 and 50 per cent* respectively(Douillard et al., The Lancet 2000, vol 355, pp 1041-1047; de Gramont et al.,Journal of Clinical Immunology 2000, vol 18, pp2938 -2947). However, a precisecomparison with the TroVax trials is not possible owing to differences in thetrial protocols and patient numbers. Data from the two Phase II trials of TroVax will be presented at the AmericanSociety of Clinical Oncology (ASCO) meeting in Orlando, USA, in May 2005. Thetrials are on track to report full safety and immunological data as well asfinal tumour response statistics in the second half of 2005. Patient survival,which can be compared to historical controls, will be reported once the mediansurvival has been reached in the two trials. This is anticipated towards the endof 2005. A more detailed report of these two trials of TroVax with first linechemotherapy is set out below: (i) TroVax plus IFL chemotherapy In the trial of TroVax plus irinotecan, 5-flourouracil and leucovorin, achemotherapy combination known as IFL, 19 patients have been recruited. Thetreatment regimen comprises six immunisations of TroVax and up to 12 cycles ofchemotherapy. 13 patients have reached the preliminary analysis stage, and all13 have mounted anti-5T4 immune responses. Clinical and tumour responses have been assessed in 11 patients that havereceived four TroVax immunisations and completed chemotherapy treatment. Ten of11 patients responded to treatment. Three patients had stable disease, whileseven patients (64 per cent*) mounted clinical responses, comprising onecomplete response and six partial responses. For reference, the two-arm pivotaltrial that supported approval of IFL chemotherapy alone in first line treatmentof metastatic colorectal cancer, in a total of 338 patients, showed a clinicalresponse rate of 41 per cent* for the evaluable IFL group (Douillard et al.,2000). (ii) TroVax plus FOLFOX chemotherapy The TroVax plus FOLFOX trial has recruited 17 patients, similarly receiving siximmunisations of TroVax alongside chemotherapy. The current status is that 12patients have reached the preliminary stage for immunological analysis and eightpatients are evaluable for tumour responses. At the preliminary stage of fourTroVax immunisations and eight cycles of chemotherapy, all 12 patients havemounted anti-5T4 immune responses. Clinical responses were observed in six of the eight (75 per cent*) presentlyevaluable patients, comprising two complete responses and four partialresponses. The two other evaluable patients experienced disease stabilisationfollowing treatment, meaning that 100 per cent of evaluable patients respondedto treatment. An independent two-arm trial with a comparable FOLFOX chemotherapyregimen and enrolment criteria, reported a confirmed clinical response rate of50 per cent* and a tumour response rate, which includes disease stabilisation,of 82 per cent in a total of 420 patients (de Gramont et al., 2000). Phase II trial of TroVax in patients undergoing surgery for resectable livermetastases An investigator initiated, open label Phase II trial started in 2004, withsponsorship from Cancer Research UK, in colorectal cancer patients who haveoperable liver metastases. Patients receive TroVax immunisations before(neoadjuvant) and after (adjuvant) surgery. Recruitment into this 20-patienttrial is over halfway completed. Eleven patients have received the initial regimen of TroVax immunisations, twoof which were subsequently withdrawn for being ineligible for surgery. The eightevaluable patients have achieved the primary endpoint of immune responses to the5T4 tumour antigen, and are eligible for further TroVax doses. The most recentpatient has not progressed far enough through the trial to assess immuneresponsiveness. TroVax has been safe and well tolerated in all patients treatedto date in this trial. The treatment schedule comprises two immunisations with TroVax before and afterliver surgery and, potentially, a further two vaccinations. The endpoints of thestudy are safety, immunological responses to 5T4 and clinical benefit. Followingsurgery, these patients have a lower tumour burden and longer survivalexpectation than patients in Oxford BioMedica's other Phase II trials incolorectal cancer. This potentially makes them even more responsive toimmunotherapy approaches such as TroVax. Patients are generally not givenchemotherapy following liver surgery and there is a need for safe and effectivetreatments to help prevent disease relapse. Full results from this Phase II trial of TroVax in the (neo) adjuvant setting ofcolorectal cancer treatment will be published in an appropriate clinical journalby Cancer Research UK once the study is completed. Conclusion More than 65 patients with colorectal cancer have been treated with TroVax todate in four clinical trials. Across all the trials, the safety profile ofTroVax has been excellent and the majority (98 per cent) of assessable patients(50 patients) have mounted immune responses following treatment with TroVax.This is an exceptionally high response rate in the context of clinical studieswith other cancer vaccines (Mocellin et al., Lancet Oncology 2004; vol 5:681-9). TroVax has been investigated in different settings in these trials -first line treatment with chemotherapy, second line treatment and the (neo)adjuvant setting with surgery - and achieved its primary endpoints in eachsetting. These data suggest that TroVax has therapeutic potential across all stages ofcolorectal cancer, supporting the notion that the product may reach largemarkets in this indication. The Company and its clinical advisors are refining a strategy to achievepotential product registration of TroVax in 2008-09. This will provide OxfordBioMedica and its potential partners with a clear and rapid route to productcommercialisation. Other TroVax trials In addition to the three ongoing Phase II trials in colorectal cancer, OxfordBioMedica is expanding the opportunity for TroVax to other tumour types. TheCompany believes that metastatic renal cell carcinoma (RCC) offers an attractivecommercial opportunity for the development of TroVax. Studies show that the 5T4antigen is present on over 90 per cent of RCC samples; current treatment optionsare ineffective or have serious side effects; and TroVax could benefit fromorphan drug and fast track designations in this indication. A Phase II trial in RCC with TroVax alongside high dose interleukin-2 isunderway in the United States. Preliminary immunology data are expected aroundmid-2005. In breast cancer, the Southwest Oncology Group, which is a US clinicaltrials consortium, is expected to start a Phase II trial in late stage patients,in 2005. -Ends- * Clinical response data from Oxford BioMedica's Phase II trials are unaudited.They are based on patients that are evaluable and use the industry standardResponse Evaluation Criteria in Solid Tumours (RECIST). The data from the trialsof the chemotherapy agents alone, cited in this press release, are derived fromevaluable patients, using clinical response criteria set by the World HealthOrganisation (WHO). The criteria defined by RECIST and WHO are similar but notidentical. A telephone conference for analysts, to discuss today's announcement, will beheld at 12:00pm today. Professor Alan Kingsman, CEO, will host the call. Apresentation of the trial data will be available on the Company's website from11:30am. http://www.oxfordbiomedica.co.uk/ Conference call dial-in details are available from Buchanan Communications.Please contact Mary-Jane Johnson on telephone no. 020 7466 5000. For further information, please contact:Oxford BioMedica plc:Professor Alan Kingsman, Chief Executive Tel: +44 (0)1865 783 000Nick Woolf, SVP Corporate StrategyCity/Financial Enquiries:Lisa Baderoon/ Mark Court/ Mary-Jane Johnson Buchanan Tel: +44 (0)20 7466 5000Communications Scientific/Trade Press Enquiries:Sue Charles/ Katja Stout/ Ashley Lilly Tel: +44 (0)20 7886 8150 Northbank CommunicationsCR-UK Contact Details:Steve Palmer Tel: +44 (0)20 7061 8312 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 the areas ofoncology and neurotherapy. The Company was established in 1995 as a spin outfrom Oxford University, 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 an immunotherapy and a gene therapy in multiple Phase II trials, and apreclinical targeted antibody therapy in collaboration with Wyeth. Inneurotherapy, the Company's lead product is a gene therapy for Parkinson'sdisease, which is expected to enter clinical development in 2005, and fourfurther preclinical candidates. The Company is underpinned by over 80 patentfamilies, which represent one of the broadest patent estates in the field. The Company has a staff of approximately 65 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, Amersham,Viragen, MolMed and Kiadis; and has licensed technology to a number of companiesincluding Merck & Co and Biogen Idec. Further information is available at www.oxfordbiomedica.co.uk. 2. TroVax(R) cancer immunotherapy 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 protein. Two Phase I/II trials with TroVax have been completed in the UK in late stagecolorectal cancer patients. The results showed that the product is safe; thatpatients mount an anti-5T4 immune response; and that the immune responsecorrelates, with high significance, to time to disease progression, whichtranslates into a correlation with improved overall survival. Four Phase II trials are underway. The trials are investigating TroVax incolorectal cancer in combination with first line standard of care treatment andas a (neo) adjuvant to surgery; and in renal cell carcinoma. The US SouthwestOncology Group is planning an additional Phase II trial in breast cancer. 3. Colorectal cancer Every year, about one million new cases of colorectal cancer are diagnosedworldwide. It is the second leading cause of cancer death in the US and thethird most frequently diagnosed cancer, according to the American CancerSociety. More than 56,000 people die from colorectal cancer in the US each yearand about 94,000 people in Europe. Colorectal cancer begins in the cells that line the colon or rectum. Colorectalcancer staging describes how advanced the cancer is. The most severe is StageIV, which defines cancers that have spread to other parts of the body such asthe liver or lungs. In the US, the current standard of care for first line treatment of Stage IVcolorectal cancer is the chemotherapy combination of irinotecan, 5-fluorouracil(5FU) and leucovorin, a combination known as IFL. In Europe, the most commontreatment is oxaliplatin, 5FU and leucovorin, a combination referred to asFOLFOX. The leading branded products are Pfizer's Camptosar(R)/Campto(R)(irinotecan) and Sanofi-Aventis' EloxatinTM (oxaliplatin). Combined sales ofthese products exceeded $2.1 billion in 2004. A new first line treatment option received approval from the US FDA in February2004. The product, AvastinTM (bevacizumab) from Genentech and Roche is atherapeutic antibody deigned to inhibit vascular endothelial growth factor, aprotein that plays a role in tumour angiogenesis and maintenance of existingtumour vessels. Avastin is approved for use in combination with 5FU basedchemotherapy regimens, including both IFL and FOLFOX. First year sales ofAvastin in 2004 were $554 million. Despite the improvements in treatment, the available options remainunsatisfactory to colorectal cancer patients, and there is a need for newtherapies offering improved efficacy, tolerability and convenience. 4. Cancer Research UK Cancer Research UK's vision is to conquer cancer through world-class research.The charity works alone and in partnership with others to carry out researchinto the biology and causes of cancer, to develop effective treatments, improvethe quality of life for cancer patients, reduce the number of people gettingcancer and to provide authoritative information on cancer. Cancer Research UK isthe world's leading independent charity dedicated to research on the causes,treatment and prevention of cancer. For further information about Cancer Research UK's work or to find out how tosupport the charity, please call +44 (0)20 7009 8820 or visit http://www.cancerresearchuk.org/ This information is provided by RNS The company news service from the London Stock Exchange