Protherics PLC and AstraZeneca Updates CytoFab(TM) Development Programme
Friday November 3, 2:03 am ET
Cheshire, UK--(MARKET WIRE)--Nov 3, 2006 --
Protherics PLC
AstraZeneca Updates CytoFab(TM) Development Programme
London, UK; Brentwood, TN, US; 3 November 2006 - Protherics PLC ("Protherics" or the "Company") and AstraZeneca today announce AstraZeneca's intention to expand the development plan for CytoFab(TM), a treatment for severe sepsis, with the addition of a 480 - patient Phase II study programme.
AstraZeneca has recently completed consultations with regulators in the US and EU. These consultations confirmed that a single Phase III study could be sufficient for regulatory approval. Furthermore, to meet the regulatory needs of both agencies, it is required that AstraZeneca implement a Phase II study programme to support the single global Phase III study.
Data from Phase II will be used to more accurately estimate the number of patients required, and confirm the appropriate dose for the Phase III study, as well as providing further supporting efficacy and safety data. This may enable a shorter timetable for the Phase III programme than originally anticipated by AstraZeneca.
The Phase II programme will start in the second half of 2007 and is expected to last up to 21 months. It will be immediately followed by the initiation of the Phase III study in the US, EU and Japan.
Under the terms of the licensing agreement, AstraZeneca is responsible for conducting and funding the global development of CytoFab(TM) and Protherics is responsible 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 clinically meaningful result with CytoFab(TM), in a single, global Phase III study, while ensuring an acceptable time to market. To increase the likelihood of success in this complex disease and reflecting the changing regulatory environment for biologics, we have made the decision to undertake additional clinical work. We hope that this will help to reduce the size of and the time needed to complete the Phase III study. We believe that this development plan will give us the best chance of successful registration for this exciting treatment."
Andrew Heath, Chief Executive of Protherics, said:
"CytoFab(TM) represents a major market opportunity and AstraZeneca's proposed development programme provides the treatment with the best route to registration. We now have a clear view of the steps needed to make this important new treatment available to sepsis patients worldwide."
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A conference call for analysts will take place today at 08.15 UK time. Please call Mo Noonan on +44 (0) 20 7831 3113 for further details.
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Protherics
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Jonathan Hunt +44 (0) 207 304 5087
Jorgen Winroth +1 (212) 579 0506
Ed 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 its global development and commercialisation in an agreement worth up to GBP195M ($340M) to Protherics in upfront and milestone payments; Protherics will receive an additional 20% royalty on global net product sales. Protherics is responsible for the supply of CytoFab(TM) bulk drug substance and will receive additional supply payments.
Effective neutralisation of TNF-alpha
TNF-alpha is an inflammatory mediator strongly implicated in sepsis, an inflammatory syndrome. Polyclonal antibody fragments are well suited to the in situ neutralisation of TNF-alpha for two main reasons. Firstly, polyclonal antibodies are polyvalent, allowing multiple antibody fragments to bind TNF-alpha and thus achieve greater neutralisation of TNF-alpha compared to monoclonal antibodies. Secondly, antibody fragments (Fabs) are much smaller than whole antibody Immunoglobulin G molecules (IgG). As a result, they have a much greater volume of distribution, with more rapid tissue penetration and clearance from the body than monoclonal antibodies.
Encouraging Phase IIb data
A phase IIb study was conducted in 19 centres in North America and was coordinated by the leading sepsis investigator, Professor Gordon R. Bernard, M.D., Director, Division of Allergy, Pulmonary and Critical Care, Vanderbilt University. The trial was a double blind placebo controlled randomised study involving 81 patients with either septic shock or sepsis with multiple organ dysfunctions.
Two hours after initiation of treatment, TNF-alpha became undetectable in all patients receiving CytoFab(TM) who had detectable levels pre-treatment whereas levels in the placebo group remained at baseline. TNF-alpha remained significantly (p < 0.050) lower in the CytoFab(TM) group throughout the 120 hour infusion period. CytoFab(TM) also significantly decreased TNF-alpha in bronchoalveolar lavage (BAL) fluid (p < 0.001).
Patients who received CytoFab(TM) had more shock-free days than those who received placebo (10.7 vs 9.4, p = 0.259), by day 14, and spent significantly more time off a ventilator (15.6 vs 9.8 ventilator-free days, p = 0.021) and 5 days less in an ICU (12.6 vs 7.6 ICU-free days, p = 0.030) by day 28. There was an encouraging trend to lower mortality at 28-days in the CytoFab(TM) group relative to the placebo group (26% vs 37%, p = 0.274). There were no differences in the incidence 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 adverse events that were considered definitely, possibly or probably related to treatment with CytoFab(TM). However, out of 110 sepsis patients who received CytoFab(TM), there were 7 patients who experienced events of uncertain causality that are consistent with adverse events experienced by patients receiving other ovine Fab products, including 1 episode of pruritis, 2 episodes of wheezing, and 4 episodes of rash.
Approved technology platform
CytoFab(TM) is based on the same technology platform, ovine polyclonal Fabs, as Protherics' CroFab(TM) (pit viper antivenom) and DigiFab(TM) (digoxin antidote) which have been approved and are currently marketed in the US. Protherics is the commercial manufacturer of these products. |
