3rd Nov 2006 07:01
Protherics PLC03 November 2006 Protherics PLC AstraZeneca Updates CytoFab(TM) Development Programme London, UK; Brentwood, TN, US; 3 November 2006 - Protherics PLC ("Protherics" orthe "Company") and AstraZeneca today announce AstraZeneca's intention to expandthe development plan for CytoFab(TM), a treatment for severe sepsis, with theaddition of a 480 - patient Phase II study programme. AstraZeneca has recently completed consultations with regulators in the US andEU. These consultations confirmed that a single Phase III study could besufficient for regulatory approval. Furthermore, to meet the regulatory needsof both agencies, it is required that AstraZeneca implement a Phase II studyprogramme to support the single global Phase III study. Data from Phase II will be used to more accurately estimate the number ofpatients required, and confirm the appropriate dose for the Phase III study, aswell as providing further supporting efficacy and safety data. This may enable ashorter timetable for the Phase III programme than originally anticipated byAstraZeneca. The Phase II programme will start in the second half of 2007 and is expected tolast up to 21 months. It will be immediately followed by the initiation of thePhase III study in the US, EU and Japan. Under the terms of the licensing agreement, AstraZeneca is responsible forconducting and funding the global development of CytoFab(TM) and Protherics isresponsible for product supply. John Rex, Vice-President, Medical Director for Infection, AstraZeneca, said: "Our goal is to optimise the chances of showing a statistically and clinicallymeaningful result with CytoFab(TM), in a single, global Phase III study, whileensuring an acceptable time to market. To increase the likelihood of success inthis complex disease and reflecting the changing regulatory environment forbiologics, we have made the decision to undertake additional clinical work. Wehope that this will help to reduce the size of and the time needed to completethe Phase III study. We believe that this development plan will give us the bestchance of successful registration for this exciting treatment." Andrew Heath, Chief Executive of Protherics, said: "CytoFab(TM) represents a major market opportunity and AstraZeneca's proposeddevelopment programme provides the treatment with the best route toregistration. We now have a clear view of the steps needed to make thisimportant new treatment available to sepsis patients worldwide." | Ends | A conference call for analysts will take place today at 08.15 UK time. Pleasecall Mo Noonan on +44 (0) 20 7831 3113 for further details. For further information please contact: ProthericsAndrew Heath, CEO +44 (0) 20 7246 9950Nick Staples, Director of Corporate Affairs +44 (0) 7919 480510Saul Komisar, President Protherics Inc +1 615 327 1027 Financial Dynamics - press enquiriesLondon: Ben Atwell, David Yates, Anna Keeble +44 (0) 20 7831 3113New York: John Capodanno, Jonathan Birt +1 212 850 5600 AstraZeneca - Media EnquiriesEdel McCaffrey +44 (0) 207 304 5034Steve Brown +44 (0) 207 304 5033Chris Major +44 (0) 207 304 5028 AstraZeneca - Investor RelationsMina Blair +44 (0) 207 304 5084Jonathan Hunt +44 (0) 207 304 5087Jorgen Winroth +1 (212) 579 0506Ed Seage +1 302 886 4065 Or visit www.protherics.com Notes for Editors: About CytoFab(TM) CytoFab(TM) is a first in class anti-TNF-alpha polyclonal antibody fragment (Fab)product, which is being developed for the treatment of severe sepsis. AstraZeneca licensing deal CytoFab(TM) has been out-licensed to AstraZeneca, which is responsible for itsglobal development and commercialisation in an agreement worth up to £195M($340M) to Protherics in upfront and milestone payments; Protherics will receivean additional 20% royalty on global net product sales. Protherics isresponsible for the supply of CytoFab(TM) bulk drug substance and will receiveadditional supply payments. Effective neutralisation of TNF-alpha TNF-alpha is an inflammatory mediator strongly implicated in sepsis, aninflammatory syndrome. Polyclonal antibody fragments are well suited to the insitu neutralisation of TNF-alpha for two main reasons. Firstly, polyclonalantibodies are polyvalent, allowing multiple antibody fragments to bindTNF-alpha and thus achieve greater neutralisation of TNF-alpha compared tomonoclonal antibodies. Secondly, antibody fragments (Fabs) are much smallerthan whole antibody Immunoglobulin G molecules (IgG). As a result, they have amuch greater volume of distribution, with more rapid tissue penetration andclearance from the body than monoclonal antibodies. Encouraging Phase IIb data A phase IIb study was conducted in 19 centres in North America and wascoordinated by the leading sepsis investigator, Professor Gordon R. Bernard,M.D., Director, Division of Allergy, Pulmonary and Critical Care, VanderbiltUniversity. The trial was a double blind placebo controlled randomised studyinvolving 81 patients with either septic shock or sepsis with multiple organdysfunctions. Two hours after initiation of treatment, TNF-alpha became undetectable in allpatients receiving CytoFab(TM) who had detectable levels pre-treatment whereaslevels in the placebo group remained at baseline. TNF-alpha remainedsignificantly (p < 0.050) lower in the CytoFab(TM) group throughout the 120 hourinfusion period. CytoFab(TM) also significantly decreased TNF-alpha inbronchoalveolar lavage (BAL) fluid (p < 0.001). Patients who received CytoFab(TM) had more shock-free days than those who receivedplacebo (10.7 vs 9.4, p = 0.259), by day 14, and spent significantly more timeoff a ventilator (15.6 vs 9.8 ventilator-free days, p = 0.021) and 5 days lessin an ICU (12.6 vs 7.6 ICU-free days, p = 0.030) by day 28. There was anencouraging trend to lower mortality at 28-days in the CytoFab(TM) group relativeto the placebo group (26% vs 37%, p = 0.274). There were no differences in theincidence of adverse events or in laboratory or vital sign abnormalities,between groups. The full Phase IIb data has been published recently in Critical Care Medicine(2006; 34(9):2271-2281), a leading peer reviewed journal. Important safety data In clinical studies of CytoFab(TM) in sepsis to date, there have been no adverseevents that were considered definitely, possibly or probably related totreatment with CytoFab(TM). However, out of 110 sepsis patients who receivedCytoFab(TM), there were 7 patients who experienced events of uncertain causalitythat are consistent with adverse events experienced by patients receiving otherovine Fab products, including 1 episode of pruritis, 2 episodes of wheezing, and4 episodes of rash. Approved technology platform CytoFab(TM) is based on the same technology platform, ovine polyclonal Fabs, asProtherics' CroFab(TM) (pit viper antivenom) and DigiFab(TM) (digoxin antidote)which have been approved and are currently marketed in the US. Protherics isthe commercial manufacturer of these products. About Sepsis Sepsis occurs when the body's immune system sets off a chain reaction and "overreacts" to an infection. Rather than being localized to the site ofinfection, the severe immune response develops throughout the body. A personsuffering from sepsis can rapidly deteriorate, with the systemic response to aninfection distorting the body's natural balance and damaging one or more vitalorgans. A patient can continue to deteriorate into septic shock, where bloodpressure falls dangerously low and many organs malfunction because of inadequateblood flow. Sepsis remains a significant problem in medical management, with anannual world wide incidence of about 3 million and a 30% mortality rate. About AstraZeneca AstraZeneca is a major international healthcare business engaged in theresearch, development, manufacture and marketing of prescription pharmaceuticalsand the supply of healthcare services. It is one of the world's leadingpharmaceutical companies with healthcare sales of $23.95 billion and leadingpositions in sales of gastrointestinal, cardiovascular, neuroscience,respiratory, oncology and infection products. AstraZeneca is listed in the DowJones Sustainability Index (Global) as well as the FTSE4Good Index. About Protherics Protherics (LSE: PTI, NASDAQ: PTIL) is an integrated biopharmaceutical companyfocused on the development, manufacture and marketing of specialist products forcritical care and oncology. Protherics' strategy is to use the revenues generated from its marketed productsto help fund the advancement of its development pipeline. With a proven trackrecord, Protherics' goal is to develop and attract additional critical care andcancer products for its sales and marketing teams to distribute in the US andEurope. The most advanced products in the Company's portfolio are Voraxaze(TM), which isexpected to be approved in the US and EU in 2007, subject to regulatory reviews,as an intervention when methotrexate blood levels remain dangerously highfollowing high doses for the treatment of cancer and CytoFab(TM), which is beingdeveloped by AstraZeneca, initially for severe sepsis, and is expected to startan additional Phase II study in 2007. Additional products in development include Prolarix(TM), a targeted cancer therapyfor primary liver cancer and other select tumours, currently in Phase I with aPhase IIa study planned for 2007 and Angiotensin Therapeutic Vaccine for thetreatment of hypertension, where encouraging phase 2a results have beendemonstrated and another phase 2a is planned with an improved formulation in2007. The majority of the Company's sales revenues (£17.7m in the year ended 31 March2006) are derived from two critical care products, CroFab(TM) (pit viperantivenom) and DigiFab(TM) (digoxin antidote) which were developed by Prothericsand are sold, in the US, through Fougera Inc, a division of Altana AG. With headquarters in London, the Company has approximately 200 employees acrossits operations in the UK, US and Australia. For further information visit: www.protherics.com Disclaimer This document contains forward-looking statements that involve risks anduncertainties, including with respect to Protherics' product pipeline andanticipated development and clinical trials for product candidates. Although webelieve that the expectations reflected in such forward-looking statements arereasonable at this time, we can give no assurance that such expectations willprove to be correct. Given these uncertainties, readers are cautioned not toplace undue reliance on such forward-looking statements. Actual results coulddiffer materially from those anticipated in these forward-looking statements dueto many important factors, including the factors discussed in Protherics' AnnualReport on Form 20-F and other reports filed from time to time with the U.S.Securities and Exchange Commission. We do not undertake to update any oral orwritten forward-looking statements that may be made by or on behalf ofProtherics. This information is provided by RNS The company news service from the London Stock ExchangeRelated Shares:
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