Xenova and FDA reach agreement on SPA
Phase III trial programme for TransMID(TM)
Enrolment to Begin Immediately
Slough, UK, 11 May 2004 - Xenova Group plc (LSE: XEN; NASDAQ: XNVA)
announced today that it has reached agreement with the US Food and
Drug Administration (FDA) under the Special Protocol Assessment (SPA)
procedure for the revised Phase III clinical trial programme proposed
Prior to its acquisition by Xenova, KS Biomedix Holdings plc (KS
Biomedix) had obtained FDA agreement for a single Phase III clinical
trial for TransMIDTM under the SPA process. Following the
acquisition of KS Biomedix, Xenova submitted a revised programme
involving two smaller sequential Phase III clinical trials rather
than one larger study, which has now been agreed with the FDA. The
adoption of a two study approach reduces the level of risk associated
with a large single study.
The initial Phase III clinical trial is designed to enrol 323
patients with non-resectable, progressive or recurrent Glioblastoma
Multiforme (GBM) who have failed conventional therapy. The study
will be a randomised, open-labelled, multi-centre trial and will
compare TransMIDTM against a number of presently used
chemotherapeutic agents regarded as "best standard of care" (BSC).
The 323 patients will be randomised in a 2:1 ratio of TransMIDTM:BSC
across approximately 50 sites in the EU, Israel and North America.
The primary end-point is overall survival time with a planned interim
analysis to be conducted after 50% of the required events have been
observed. In an earlier, open label, Phase II study, patients
receiving TransMIDTM achieved a significant increase in overall
survival compared with historical survival figures. In this study,
median survival for patients receiving TransMIDTM was approximately
37 weeks. This compares to the average life expectancy for these
patients which is currently approximately 26 weeks.
Edward Oldfield MD, Chairman of the Surgical Neurology Branch of the
National Institute of Neurological Disorders and Stroke (NINDS) at
the National Institutes of Health, Bethesda, Maryland said:
"Glioblastoma Multiforme has been a very difficult tumour to treat.
This novel approach combines a potent new drug with a targeted
delivery method that can distribute the drug directly to the region
involved with tumour. In earlier Phase I and Phase II clinical
trials, the combination produced complete and partial radiographic
responses in several patients."
David A Oxlade, Chief Executive Officer said: "We are pleased to have
reached agreement with FDA for the revised programme and we will be
starting to enrol patients immediately. People with non-resectable
Glioblastoma Multiforme currently have few treatment options and
there is a clear need for improved outcomes for these patients."
TransMIDTM received Fast Track status from the FDA in August 2001 and
orphan drug status in December 2001. In addition, the European
Commission granted TransMIDTM orphan designation in March 2002.
Xenova Group plc is a UK-based biopharmaceutical company focused on
the development of novel drugs to treat cancer and addiction with a
secondary focus in immunotherapy. The Group has a broad pipeline of
products in clinical development, including three cancer programmes:
its lead product TransMIDTM, for the treatment of high-grade glioma,
now beginning Phase III trials, and the novel DNA targeting agents
and XR303 both in Phase I for cancer indications. In addition to its
cancer drugs, Xenova is developing two therapeutic vaccines for
cocaine and nicotine addiction, in Phase II and Phase I trials
respectively. In April 2001 Xenova acquired Cantab Pharmaceuticals
plc and in September 2003 it acquired KS Biomedix Holdings plc.
Quoted on the London Stock Exchange (XEN) and on NASDAQ (XNVA),
Xenova employs approximately 112 people throughout its sites in the
UK and North America. (Reuters XEN.L; Bloomberg XEN LN).
Notes to Editors
TransMIDTM is a treatment initially being developed for high-grade
glioma (a type of brain cancer), a disease for which improved
treatment is essential, as there remains a poor prognosis for
patients. TransMIDTM is a modified diphtheria toxin conjugated to
transferrin. When TransMIDTM binds to transferrin receptors on the
surface of the cell, the diphtheria toxin gains entry to the cell.
Once inside the cell, the diphtheria toxin interferes with protein
synthesis and ultimately kills the cell. Transferrin receptors are
particularly prevalent on rapidly dividing cells, and the high level
of transferrin receptor expression on glioma cells relative to normal
brain tissue makes transferrin an appropriate targeting mechanism for
the diseased cells.
TransMIDTM is pumped directly into the brain tumour using CED
(Convection Enhanced Delivery - licensed from the National Institutes
of Health, Bethesda, Maryland, USA). CED enhances the distribution
of TransMIDTM through the tumour mass and produces high local
concentrations of drug. TransMIDTM is directly infused into the
tumour in order to reduce systemic side effects. This also has the
benefit of circumventing the usual obstacles present in drug delivery
to the brain caused by the blood-brain barrier.
Phase I and Phase II clinical trials for TransMIDTM have been
successfully completed in patients suffering from inoperable,
recurrent high grade gliomas who have failed to respond to other
forms of treatment. A Phase I dose-escalating study was performed at
the National Institutes of Health in the US and was followed by a
Phase II multi-centre study at nine premier US medical centres.
In a Phase II study, 50% or greater reduction in tumour volume was
noted in 35% of evaluable patients, with a corresponding increase in
life expectancy in those patients that did respond. Median survival
time for patients receiving TransMIDTM was approximately 37 weeks.
This compares to the average life expectancy of approximately 26
weeks for patients with this condition being treated with best
standard of care.
TransMIDTM is currently licensed to Nycomed Denmark A/S in Europe,
Sosei Co Ltd in Japan, Medison Pharma Ltd in Israel and Ranbaxy
Laboratories Limited in India. The rights to TransMIDTM in North
America have been retained.
Convection Enhanced Delivery
Convection enhanced delivery (CED) involves the slow continuous
infusion of TransMIDTM over several days via one or more catheters
directly into the tumour. This technique maximises perfusion of the
drug into the target area. Xenova has an exclusive license from the
NIH for the use of CED with TransMIDTM for cancers of the CNS, head
Special Protocol Assessment
The Prescription Drug User Fee Act of 1992 (PDUFA) goals for special
protocol assessment and agreement provide that, upon request, FDA
will evaluate within 45 days certain protocols and issues relating to
the protocols to assess whether they are adequate to meet scientific
and regulatory requirements identified by the sponsor. Three types
of protocols related to PDUFA products are eligible for this special
protocol assessment under the PDUFA goals: (1) animal carcinogenicity
protocols, (2) final product stability protocols, and (3) clinical
protocols for Phase III trials whose data will form the primary basis
for an efficacy claim if the trials had been the subject of
discussion at an end-of-Phase II/pre-Phase III meeting with the
review division. For more information on Special Protocol
Assessment, please visit www.fda.gov.
For further information about Xenova and its products please visit
the Xenova website at www.xenova.co.uk
For Xenova: Disclaimer to take advantage of the "Safe Harbor"
provisions of the US Private Securities Litigation Reform Act of
1995. This press release contains "forward-looking statements,"
including statements about the discovery, development and
commercialization of products. Various risks may cause Xenova's
actual results to differ materially from those expressed or implied
by the forward looking statements, including: adverse results in our
drug discovery and clinical development programs; failure to obtain
patent protection for our discoveries; commercial limitations imposed
by patents owned or controlled by third parties; our dependence upon
strategic alliance partners to develop and commercialize products and
services; difficulties or delays in obtaining regulatory approvals to
market products and services resulting from our development efforts;
the requirement for substantial funding to conduct research and
development and to expand commercialization activities; and product
initiatives by competitors. For a further list and description of
the risks and uncertainties we face, see the reports we have filed
with the Securities and Exchange Commission. We disclaim any
intention or obligation to update or revise any forward-looking
statements, whether as a result of new information, future events or
Xenova Group plc
+44 (0)1753 706600
David A Oxlade, Chief Executive Officer
Daniel Abrams, Group Finance Director
Veronica Cefis Sellar, Head of Corporate Communications
UK - Financial Dynamics
+44 (0)20 7831 3113
US - Trout Group BMC Communications
+1 212 477 9007
Media: Brad Miles, ext 17
Investors: Lee Stern, ext 22
---END OF MESSAGE--