22nd Jan 2008 07:00
Protherics PLC22 January 2008 Protherics PLC CytoFabTM phase 2 programme in severe sepsis commenced by AstraZeneca London, UK; Brentwood, TN, US; 22 January 2008 - Protherics PLC ("Protherics" orthe "Company"), the international biopharmaceutical company focused on criticalcare and cancer, today announces that AstraZeneca has treated the first patientin its expanded phase 2 programme of CytoFabTM in severe sepsis, an inflammatorycondition resulting from uncontrolled infections. Protherics previously reported encouraging phase 2b study results in an 81patient study in severe sepsis. In December 2005, AstraZeneca and Prothericsannounced a licensing agreement for CytoFabTM, where AstraZeneca is responsiblefor its global development and commercialisation and Protherics for the supplyof CytoFabTM bulk drug substance. AstraZeneca's phase 2 programme will consist of two separate studies in patientswith severe sepsis. The first study, which is now underway, is designed toassess the safety, tolerability, pharmacokinetics and pharmacodynamics ofCytoFabTM produced by the revised, scaled up manufacturing process. It willenroll up to 70 patients across multiple sites in the US and the study isexpected to report in approximately twelve months' time. Following thesuccessful completion of this study, a second study will be conducted to assessboth the safety and the efficacy of CytoFabTM in a larger patient group. Andrew Heath, Chief Executive of Protherics commented: "We are very pleased that the first patient has been enrolled in the new CytoFabphase 2 programme and that CytoFab is once again being administered to patientswith this life-threatening condition. We have an excellent partner inAstraZeneca and look forward to further progress of CytoFab in this importantarea of critical care." Dr John Rex, Vice President Clinical Infection, AstraZeneca commented: "AstraZeneca and Protherics have both undertaken a considerable programme ofwork since the signing of the licensing agreement, and we are delighted that thephase 2 programme with CytoFab is underway". | Ends | For further information please contact: Protherics - Investor RelationsAndrew 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 - Media EnquiriesLondon: Ben Atwell, Lara Mott +44 (0) 20 7831 3113New York: John Capodanno, Jonathan Birt +1 212 850 5600 AstraZeneca - Investor RelationsMina Blair +44 (0) 207 304 5084Jonathan Hunt +44 (0) 207 304 5087Jorgen Winroth +1 (212) 579 0506Ed Seage +1 302 886 4065Karl Hard +44 207 304 5322Peter Vozzo (MedImmune) +1 301 398 4358 AstraZeneca - Media EnquiriesHelen Wailes +44 (0) 1625 510 975Edel McCaffrey +44 (0) 207 304 5034Steve Brown +44 (0) 207 304 5033 Notes for Editors: About CytoFabTM CytoFabTM is a first in class anti-TNF-alpha polyclonal antibody fragment (Fab)product, which is being developed for the treatment of severe sepsis. 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 compared to monoclonalantibodies. Secondly, antibody fragments (Fabs) are much smaller than wholeantibody Immunoglobulin G molecules (IgG). As a result, they have a muchgreater volume of distribution, with more rapid tissue penetration and clearancefrom the body than monoclonal antibodies. Encouraging phase 2b data A phase 2b 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 CytoFabTM who had detectable levels pre-treatment whereaslevels in the placebo group remained at baseline. TNF-alpha remainedsignificantly (p < 0.050) lower in the CytoFabTM group throughout the 120 hourinfusion period. CytoFabTM also significantly decreased TNF-alpha inbronchoalveolar lavage (BAL) fluid (p < 0.001). Patients who received CytoFabTM 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 CytoFabTM 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 2b data has been published in Critical CareMedicine (2006; 34(9):2271-2281). Important safety data In clinical studies of CytoFabTM in sepsis to date, there have been no adverseevents that were considered definitely, possibly or probably related totreatment with CytoFabTM. However, out of 110 sepsis patients who receivedCytoFabTM, 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 CytoFabTM is based on the same technology platform, ovine polyclonal Fabs, asProtherics' CroFabTM (pit viper antivenom) and DigiFabTM (digoxin antidote)which have been approved and are currently marketed in the US. Protherics isthe commercial manufacturer of these products. AstraZeneca licensing deal CytoFabTM has been out-licensed to AstraZeneca, which is responsible for itsglobal development and commercialisation in an agreement worth up to £195million to Protherics in upfront and milestone payments; Protherics will receivean additional 20% royalty on global net product sales. Protherics isresponsible for the supply of CytoFabTM bulk drug substance and will receiveadditional payments for supply. Protherics has received a total of £26.3 millionin milestone payments since the agreement was signed in December 2005. On 3 November 2006, AstraZeneca announced its intention to undertake anadditional phase 2 programme in the second half of 2007 with CytoFabTM prior tothe initiation of the phase 3 study in the US, EU and Japan. 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 Protherics Protherics (LSE: PTI, NASDAQ: PTIL) is a leading biopharmaceutical companyfocused on the development, manufacture and marketing of specialised productsfor critical care and cancer. Protherics has developed and manufactures two biologics for critical care whichare FDA approved and currently sold in the US: CroFabTM, a pit viper antivenomand DigiFabTM, a digoxin antidote. Protherics generated £31.1 million inrevenues in its financial year ended 31 March 2007, and reported £46.9 millionin cash at the half year ending 30 September 2007. The Company's strategy is touse the revenues generated from its marketed and out-licensed products to helpfund the advancement of its broad, late stage pipeline. Protherics has two major development opportunities in its critical careportfolio. CytoFabTM is being developed by AstraZeneca, for the treatment ofsevere sepsis, after a major £195 million licensing deal with AstraZeneca inDecember 2005. An additional, expanded phase 2 programme is underway andexpected to report in 2009. In addition, Protherics is on-track to report in thefirst half of 2008 the results of a phase 2b study with a Digoxin Immune Fab forthe treatment of pre-eclampsia. Protherics has a pipeline of four novel cancer products in clinical development,and intends to undertake the sales and marketing of these products in the US andor the EU. Protherics is preparing to resubmit a BLA for VoraxazeTM, an adjunctto high dose methotrexate therapy, under a rolling submission in the US startingin H2 2008. With headquarters in London, the Company has approximately 290 employees acrossits operations in the UK, US and Australia. For further information visit:www.protherics.com 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 $26.47 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. 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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