Xenova Group PLC
14 May 2001
FOR IMMEDIATE RELEASE
Xenova Group plc Reports Positive Data from 2 Phase IIa Clinical Studies of
P-glycoprotein inhibitor XR9576
Slough, UK, 14 May, 2001 - Xenova Group plc (Nasdaq NM: XNVA; London Stock
Exchange: XEN) today presented results from two Phase IIa pharmacokinetic
studies of the drug development candidate XR9576 at the annual meeting of the
American Society of Clinical Oncology in San Francisco, Cal. on Saturday 12
May, 2001. Up to 90 per cent of cancer patients may develop resistance to
current anti-cancer drugs and P-glycoprotein related multi-drug resistance is
the most common form of this phenomenon. XR9576 is a potent small-molecule
inhibitor of the P-glycoprotein pump and is the product of Xenova's in-house
research and development. It is being developed to restore the sensitivity of
multi-drug resistant cancer cells to specific anti-cancer drugs.
In an open label Phase IIa study, the pharmacokinetic and pharmacodynamic
interactions of a 150mg fixed single dose of XR9576, 175mg/m(2) of the
cytotoxic drug paclitaxel and the combination of the two were evaluated in
twelve patients with recurring ovarian cancer. XR9576 was given as a 30 minute
infusion and paclitaxel as a 3 hour infusion, starting one and a half hours
after the end of the XR9576 infusion. Patients received up to a total of five
cycles of XR9576 and paclitaxel at three weekly intervals in combination with
The study showed that the combination treatment was well tolerated and that
the combination of XR9576, paclitaxel and carboplatin gave responses in five
out of the twelve patients, as assessed by independent review of CT scans and
that seven out of the twelve patients received symptomatic benefit. Two of
these patients obtained a complete remission of six and ten months post
treatment respectively. Two patients obtained a partial remission and three
had disease stabilization. The study was conducted in conjunction with the
Royal Surrey County Hospital, Guildford, UK.
The results of a further open label Phase IIa study for XR9576, conducted in
conjunction with the National Cancer Institute, Washington, DC, were also
presented at the same meeting. The twenty five patient study was established
to determine the safety of XR9576 when given in combination with the cytotoxic
drug vinorelbine and to determine the extent, if any, of a pharmacokinetic
interaction. The study concluded that a vinorelbine dose of 20mg/m(2) can be
safely administered in combination with a single 150mg dose of XR9576 and that
a single dose of XR9576 did not significantly affect the pharmacokinetics of
vinorelbine. The study additionally showed that a single 150mg dose of XR9576
inhibits P-glycoprotein-mediated rhodamine efflux from circulating CD56+ cells
for at least 48 hours and that this dose also inhibited the clearance of
99mTc-Sestamibi (an imaging agent pumped by P-gp) by the liver and some
tumours. This demonstrated the presence of P-glycoprotein expression in these
tumours, and allowed the visualization of a number of metastases. The study
concluded that XR9576 is a potent P-glycoprotein antagonist, without
significant side effects, and with less pharmacokinetic interference than
other antagonists used previously.
Dr Tito Fojo of the National Cancer Institute, and Principal Investigator for
the vinorelbine trial, commented:
'The ideal multi-drug resistance modulator should allow cytotoxic drugs to be
administered at or as close as possible to their normal dose. XR9576 itself is
non-toxic and leaves cytotoxic drug levels largely unaffected. Assays have
indicated that a single dose of XR9576 is sufficient to block the action of
the P-gp pump for in excess of 24 hours and imaging studies have also
indicated that XR9576 can effectively block the P-gp mediated efflux from
tumours. Additionally, it is encouraging to see a number of positive
responses amongst patients taking part in this study.'
The studies form part of a series of three Phase IIa pharmacokinetic studies
which have been successfully carried out by Xenova and in which XR9576 has
been given in combination with the cytotoxics paclitaxel, vinorelbine and
The study series has confirmed that at the dose levels studied, no clinically
significant pharmacokinetic interaction was observed and that the
administration of XR9576 with paclitaxel, vinorelbine and doxorubicin was well
tolerated. The cytotoxics can be used in combination with XR9576 at or close
to their normal clinical dose. The positive responses noted in several of the
patients in the studies have provided anecdotal evidence of efficacy.
Xenova has been in discussions with the FDA in the US and with a number of
regulatory agencies in Europe with respect to the further development of this
compound and the establishment of pivotal Phase III registration studies in
these countries. Licensing discussions in relation to XR9576 are underway
with a number of potential marketing partners.
Xenova Group plc Financial Dynamics
Tel: +44 (0) 1753 706600 Tel: +44(0) 207 831 3113
David Oxlade: Chief Executive Officer David Yates/Fiona Noblet
Hilary Reid Evans: Corporate Communications
Notes to Editors
Following the merger with Cantab, Xenova Group plc's product pipeline focuses
principally on the therapeutic areas of cancer, infectious diseases and
addiction. The Group has a well-established track record in the
identification, development and partnering of innovative products and
technologies. Currently, major products under development include:
XR9576 (Phase IIa clinical trials complete) - a P-gp pump inhibitor which is
designed to combat multi-drug resistance in cancer.
TA-HPV (Phase II clinical trials) - an immunotherapeutic vaccine, designed to
prevent the recurrence of cervical cancer.
TA-CIN (Phase I clinical trials) - a recombinant fusion protein, designed as a
treatment for women with cervical dysplasia.
DISC-GMCSF (Phase I clinical trials) - an immunotherapeutic vaccine designed
as a treatment for a broad range of solid tumours.
XR11576 - (Pre-clinical development) - a dual topoisomerase I and II
inhibitor, designed as an orally administrable cytotoxic.
TA-HSV (Phase II clinical trials) - a vaccine designed for the treatment of
recurrent genital herpes, partnered with GlaxoSmithKline.
DISC-PRO ((Phase I clinical trials complete) - a prophylactic vaccine designed
for the prevention of genital and oro-labial herpes.
TA-CD (Phase IIa clinical trials complete) - a vaccine for the treatment of
TA-NIC (Pre-clinical development) - a vaccine designed as a treatment for
The Group has partnerships with a number of major pharmaceutical companies
including Glaxo SmithKline, Lilly, Pfizer and Celltech.
For further information about Xenova and its products please visit the Xenova
website at www.xenova.co.uk