Geneva, Switzerland (ots/PRNewswire)
- PharmaMar presented data
from six studies, four of which were from pharmacogenomics research
projects at the EORTC-NCI-AACR International Conference on
Molecular Targets and Cancer Therapeutics, held in Geneva,
Switzerland, from 28 September to 1 October 2004.
Pharmacogenomics is the science that examines the inherited
variations in genes which dictate drug response and explores the way
these variations can be used to predict how a patient will respond to
a given drug.
PharmaMar launched its pharmacogenomics research programme two
years ago on the basis of data generated from its clinical trials of
Yondelis, Aplidin and Kahalalide F. Whereas all three of these drugs
have been shown in clinical trials to be active in pre-treated cancer
patients, as with all drugs, not all patients benefit from such
treatment. This research programme examines polymorphisms(i), gene
expression levels and gene mutations to predict the impact of a given
treatment on different groups of cancer patients and provides a tool
to develop customised chemotherapy models for individual patients.
The pharmacogenomics results presented at the EORTC-NCI-AACR
Conference reported on two studies of Yondelis, one of Aplidin and
one of Kahalalide F.
An in vitro study completed in collaboration with the Spanish
National Cancer Centre (CNIO) identified a set of genes whose
expression is correlated with sensitivity and resistance to Yondelis.
The data provides a rationale to explore at the clinical level
whether this correlation can contribute to the identification of
those patients who might benefit from Yondelis therapy.
A second, multi-centre retrospective pharmacogenomics study (UZ
Gasthuisberg (Belgium), Memorial Sloan-Kettering Cancer Centre (US)
and Hospital Universitari Germans Trias i Pujol (Spain)), aimed to
correlate some DNA polymorphisms and mRNA expression levels of some
DNA repair related genes, in paraffin embedded tumor samples, with
the clinical outcome of 53 sarcoma patients included in the study
after Yondelis therapy.
The goal of such studies was the characterisation of patients
prone to respond to Yondelis, which is a step towards the development
of customised therapeutic approaches. The results conclude that low
expression of BRCA1 mRNA is associated with better Progression Free
Survival (PFS) and statistically significant longer survival of
sarcoma patients after treatment with Yondelis and that high mRNA
expression levels of XPD or ERCC1 genes do not have a negative impact
on the clinical outcome of those patients. Also, polymorphisms
Lys751Lys and Asp312Asp genotypes in XPD gene are associated with
better clinical outcomes. These results warrant additional
prospective studies for patient selection based on molecular markers.
A preclinical study (in collaboration with the Università
Cattolica Sacro Cuore of Rome and the Istituto di Ricerche
Farmacologiche Mario Negri of Milan) on the effect of YondelisTM in
combination with Irinotecan - the topoisomerase I inhibitor - in
vitro and in vivo in xenograft models, showed that the combination of
the two drugs produced a greater anti-tumoural effect than that
achieved when each drug is given as a single agent. This result
suggests that this combination should be further studied in clinical
trials for the treatment of patients with rhabdomyosarcoma.
A fourth poster reporting on the results of a clinical trial of
Yondelis performed in San Antonio, Texas, compared the tolerability
of Yondelis when administered as a 1-hour weekly infusion with the
results of a prior study of a 3-hour infusion. The study demonstrated
that the 1-hour weekly infusion was similarly tolerated to the 3-hour
schedule and concluded that the 1-hour weekly infusion of Yondelis is
convenient, active and well tolerated. Clinical activity has been
seen in selected soft tissue sarcoma subtypes.
A study on the gene expression profiling of leukaemic blasts and
the correlation with their sensitivity to Aplidin showed that genes
in Acute Myeloblastic Leukaemia(ii) samples resistant to Aplidin are
involved mainly in NF-kB activation. In contrast, Acute Lymphoblastic
Leukaemia(iii) samples sensitive to Aplidin presented higher
expression of DNA damage response genes. The data presented supports
the idea of a differential profile applicable to leukaemic cells
sensitive to Aplidin and offers a framework for validation studies in
phase II trials. This study was completed in collaboration with CNIO
of Spain and the VU University Medical Centre of The Netherlands.
Kahalalide F (KF)
The study (conducted in collaboration with VU University Medical
Centre, Amsterdam) concluded that ErbB3 and Akt are major
determinants of the cytotoxic activity of KF in vitro. These results
should be considered in upcoming phase II clinical trials of KF.
Dr José Jimeno, VP of Scientific Development and
Pharmacogenomics Programmes at PharmaMar, said:
"Our commitment to fuse classical clinical development with a
programme of rational and ethical pharmacogenomics studies is key to
the growth strategy of Pharmamar. We believe this can only lead to
better use of our marine anticancer drugs and therefore much higher
i) Polymorphism - the occurrence of more than one form of
individual in a single species with an interbreeding population.
ii) Acute Myeloblastic Leukaemia - a form of leukaemia, which is
characterised by the proliferation of immature white blood cells
(granulocytes) in the bloodstream. Occurs primarily in adults and in
infants under 1 year of age. Complications include abnormal bleeding
and susceptibility to infections.
iii) Acute Lymphoblastic Leukaemia - the most common form of
childhood cancer. It affects lymphocytes, a type of white blood
cells. Leukaemic cells accumulate in the bone marrow, replace normal
blood cells and spread to other organs including liver, spleen, lymph
nodes, central nervous system, kidneys and gonads.
PharmaMar is a biopharmaceutical company, advancing cancer care
through the discovery and development of innovative marine-derived
medicines. PharmaMar's clinical portfolio currently includes
YondelisTM in phase II clinical trials (co-developed with Johnson &
Johnson Pharmaceutical Research & Development), designated Orphan
Drug for STS by the EMEA in 2001 and Orphan Drug for ovarian cancer
in 2003; Aplidin(R), in phase II, designated Orphan Drug for acute
lymphoblastic leukaemia by the EMEA in 2003 and by the FDA in 2004;
Kahalalide F in phase II and ES-285 in phase I clinical trials.
PharmaMar, based in Madrid, Spain, is a subsidiary of the Zeltia
Group (Spanish stock exchange: ZEL.MC; Bloomberg: ZEL SM; Reuters:
ZEL.MC). PharmaMar can be found on the Web at
 EORTC-NCI-AACR: European Organisation for Research and
Treatment of Cancer-National Cancer Institute-American Association
for Cancer Research
ots Originaltext: PharmaMar
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For more information, please contact: Lola Casals, PharmaMar, Tel:
+34-91-846-6000 David Yates & James Strong, Financial Dynamics, Tel: