Cheshire, UK--(Marketwire - January 22, 2008) -
Protherics PLC
CytoFabTM phase 2 programme in severe sepsis commenced by AstraZeneca
London, UK; Brentwood, TN, US; 22 January 2008 - Protherics PLC ("Protherics" or
the "Company"), the international biopharmaceutical company focused on critical
care and cancer, today announces that AstraZeneca has treated the first patient
in its expanded phase 2 programme of CytoFabTM in severe sepsis, an inflammatory
condition resulting from uncontrolled infections.
Protherics previously reported encouraging phase 2b study results in an 81
patient study in severe sepsis. In December 2005, AstraZeneca and Protherics
announced a licensing agreement for CytoFabTM, where AstraZeneca is responsible
for its global development and commercialisation and Protherics for the supply
of CytoFabTM bulk drug substance.
AstraZeneca's phase 2 programme will consist of two separate studies in patients
with severe sepsis. The first study, which is now underway, is designed to
assess the safety, tolerability, pharmacokinetics and pharmacodynamics of
CytoFabTM produced by the revised, scaled up manufacturing process. It will
enroll up to 70 patients across multiple sites in the US and the study is
expected to report in approximately twelve months' time. Following the
successful completion of this study, a second study will be conducted to assess
both 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 CytoFab
phase 2 programme and that CytoFab is once again being administered to patients
with this life-threatening condition. We have an excellent partner in
AstraZeneca and look forward to further progress of CytoFab in this important
area of critical care."
Dr John Rex, Vice President Clinical Infection, AstraZeneca commented:
"AstraZeneca and Protherics have both undertaken a considerable programme of
work since the signing of the licensing agreement, and we are delighted that the
phase 2 programme with CytoFab is underway".
| Ends |
For further information please contact:
Protherics - Investor Relations
Andrew Heath, CEO +44 (0) 20 7246 9950
Nick Staples, Director of Corporate Affairs +44 (0) 7919 480510
Saul Komisar, President Protherics Inc +1 615 327 1027
Financial Dynamics - Media Enquiries
London: Ben Atwell, Lara Mott +44 (0) 20 7831 3113
New York: John Capodanno, Jonathan Birt +1 212 850 5600
AstraZeneca - Investor Relations
Mina Blair +44 (0) 207 304 5084
Jonathan Hunt +44 (0) 207 304 5087
Jorgen Winroth +1 (212) 579 0506
Ed Seage +1 302 886 4065
Karl Hard +44 207 304 5322
Peter Vozzo (MedImmune) +1 301 398 4358
AstraZeneca - Media Enquiries
Helen Wailes +44 (0) 1625 510 975
Edel McCaffrey +44 (0) 207 304 5034
Steve 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, 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 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 2b data
A phase 2b 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 CytoFabTM 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 CytoFabTM group throughout the 120 hour
infusion period. CytoFabTM also significantly decreased TNF-alpha in
bronchoalveolar lavage (BAL) fluid (p < 0.001).
Patients who received CytoFabTM 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 CytoFabTM 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 2b data has been published in Critical Care
Medicine (2006; 34(9):2271-2281).
Important safety data
In clinical studies of CytoFabTM in sepsis to date, there have been no adverse
events that were considered definitely, possibly or probably related to
treatment with CytoFabTM. However, out of 110 sepsis patients who received
CytoFabTM, 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
CytoFabTM is based on the same technology platform, ovine polyclonal Fabs, as
Protherics' CroFabTM (pit viper antivenom) and DigiFabTM (digoxin antidote)
which have been approved and are currently marketed in the US. Protherics is
the commercial manufacturer of these products.
AstraZeneca licensing deal
CytoFabTM has been out-licensed to AstraZeneca, which is responsible for its
global development and commercialisation in an agreement worth up to £195
million 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 CytoFabTM bulk drug substance and will receive
additional payments for supply. Protherics has received a total of £26.3 million
in milestone payments since the agreement was signed in December 2005.
On 3 November 2006, AstraZeneca announced its intention to undertake an
additional phase 2 programme in the second half of 2007 with CytoFabTM prior to
the 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 of
infection, the severe immune response develops throughout the body. A person
suffering from sepsis can rapidly deteriorate, with the systemic response to an
infection distorting the body's natural balance and damaging one or more vital
organs. A patient can continue to deteriorate into septic shock, where blood
pressure falls dangerously low and many organs malfunction because of inadequate
blood flow. Sepsis remains a significant problem in medical management, with an
annual world wide incidence of about 3 million and a 30% mortality rate.
About Protherics
Protherics (LSE: PTI, NASDAQ: PTIL) is a leading biopharmaceutical company
focused on the development, manufacture and marketing of specialised products
for critical care and cancer.
Protherics has developed and manufactures two biologics for critical care which
are FDA approved and currently sold in the US: CroFabTM, a pit viper antivenom
and DigiFabTM, a digoxin antidote. Protherics generated £31.1 million in
revenues in its financial year ended 31 March 2007, and reported £46.9 million
in cash at the half year ending 30 September 2007. The Company's strategy is to
use the revenues generated from its marketed and out-licensed products to help
fund the advancement of its broad, late stage pipeline.
Protherics has two major development opportunities in its critical care
portfolio. CytoFabTM is being developed by AstraZeneca, for the treatment of
severe sepsis, after a major £195 million licensing deal with AstraZeneca in
December 2005. An additional, expanded phase 2 programme is underway and
expected to report in 2009. In addition, Protherics is on-track to report in the
first half of 2008 the results of a phase 2b study with a Digoxin Immune Fab for
the 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 and
or the EU. Protherics is preparing to resubmit a BLA for VoraxazeTM, an adjunct
to high dose methotrexate therapy, under a rolling submission in the US starting
in H2 2008.
With headquarters in London, the Company has approximately 290 employees across
its 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 the
research, development, manufacture and marketing of prescription pharmaceuticals
and the supply of healthcare services. It is one of the world's leading
pharmaceutical companies with healthcare sales of $26.47 billion and leading
positions in sales of gastrointestinal, cardiovascular, neuroscience,
respiratory, oncology and infection products. AstraZeneca is listed in the Dow
Jones Sustainability Index (Global) as well as the FTSE4Good Index.
Disclaimer
This document contains forward-looking statements that involve risks and
uncertainties, including with respect to Protherics' product pipeline and
anticipated development and clinical trials for product candidates. Although we
believe that the expectations reflected in such forward-looking statements are
reasonable at this time, we can give no assurance that such expectations will
prove to be correct. Given these uncertainties, readers are cautioned not to
place undue reliance on such forward-looking statements. Actual results could
differ materially from those anticipated in these forward-looking statements due
to many important factors, including the factors discussed in Protherics' Annual
Report 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 or
written forward-looking statements that may be made by or on behalf of
Protherics.
This information is provided by RNS
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