Istanbul, Turkey (ots/PRNewswire)
- PharmaMar, the
biopharmaceutical company specialising in cancer therapy, announces
today that it is to present new data from two of its clinical
compounds, Kahalalide F and Aplidin(R), at the 31st European Society
for Medical Oncology Congress (ESMO) being held in Istanbul, Turkey
from 29 September to 3 October 2006.
Data will also be presented on PharmaMar's lead cancer compound,
Yondelis(R), which demonstrate its potential in combination with
carboplatin and expand its potential range of use.
The results of three Phase II trials to evaluate the anti-tumour
activity of Kahalalide F will be presented. In all these trials
Kahalalide F was administered to patients in a weekly one hour
intravenous infusion at a dose of 650 microg/m2. The summary of the
data is as follows:
The Phase II clinical trial of Kahalalide F as a second line
therapy in patients with advanced non-small cell lung cancer (NSCLC)
was a multi-centre, non-randomised study in 31 patients. One partial
response was observed and stable disease was reported in eight
patients, with the majority of the clinical benefit being seen in
patients with squamous cell carcinoma.
The Phase II study of Kahalalide F as a first line therapy in
patients with hepatocarcinoma (HC) was a non-randomised study in 22
patients with metastatic or irresectable HC. Stable disease was
reported in ten patients (seven lasting more than three months and
four lasting more than six months). A 50% decrease in the tumour
marker alpha-fetoprotein, AFP (considered to be an indicator of
improvement) was observed in two patients.
The Phase II study of Kahalalide F in patients with advanced
malignant melanoma (AMM) enrolled 24 patients. Stable disease lasting
more than three months was reported in five patients.
In all these trials Kahalalide F was very well tolerated with
no serious adverse events reported, showing an excellent tolerability
This exploratory Phase II trial of Aplidin(R) in patients with
advanced renal or colorectal cancer was a multi-centre, open-label,
randomised clinical and pharmacokinetic study of Aplidin(R), either
alone or in combination with L-carnitine, in patients with advanced
renal or colorectal cancer in objective progression. 81 patients were
enrolled into two arms of the study, Arm A being administered
Aplidin(R) at a dose of 5 mg/m2 and Arm B at a dose of 7 mg/m2 plus
Anti-tumour activity was observed in patients with previously
treated renal cancer (partial response 5.4% and 48.7% with stable
disease). Stable disease lasting more than 12 weeks was seen in 32.4%
of renal patients. In the colorectal patients, stable disease lasting
more than 12 weeks was observed in 24.3% of patients. No difference
in efficacy was observed between the two arms of the study.
The safety profile was similar to that seen in Aplidin(R) at the
Phase I stage. The concomitant administration of L-carnitine allowed
the administration of the higher 7 mg/m2 dose of Aplidin(R) but
resulted in more severe incidence of side effects, as compared to the
5 mg/m2 dose. These data support the continuation of the clinical
development of Aplidin(R) at a dose of 5 mg/m2 in renal cancer.
The results of a combination Phase I study of carboplatin and
YONDELIS(R) (trabectedin) conducted in the UK and Spain in a total of
44 heavily pretreated ovarian patients will be presented. The data
show that the combination was well tolerated and that the most common
side effects observed were neutropenia and thrombocytopenia.
Preliminary data on this study were presented at the ESMO congress in
Anti-tumour activity in ovarian cancer after failing other
therapies was observed. Three partial responses (PR, 20%) and stable
disease in 3 patients (SD, 20%) lasting longer than 3 months were
observed, indicating that further study of the combination at the
recommended dose is warranted.
This study shows that the combination of YONDELIS(R) and
carboplatin is feasible and active at doses near the maximum for both
agents. This combination expands the potential use of YONDELIS in a
variety of tumour types in which platinum compounds are the main
The results of a Phase II trial of YONDELIS(R) administered as a
3-hour intravenous infusion in sarcoma patients also will be
presented. A total of 75 patients with Soft Tissue Sarcomas (STS),
Osteosarcomas (OS), Rhabdomyosarcomas (RMS) or the Ewing's Family
tumours (EFT) were enrolled and treated in several European
countries, having progressed through standard therapy. Preliminary
results were presented at ASCO in 2003.
The final results in STS demonstrated that YONDELIS(R) as a 3-hour
infusion is a well-tolerated and active agent in this STS population.
The data suggests the anti-tumour effect falls within the same range
as the 24-hour continuous infusion, a regimen known to be active in
STS (pivotal study STS-201 currently under registration). In
addition, the longest response was observed in a patient with a
myxoid liposarcoma, which has recently been shown to be sensitive to
this agent. In EFT and RMS, some anti-tumour activity was observed,
meriting further investigation.
Commenting on the ESMO presentations, Dr Miguel A. Izquierdo,
PharmaMar's Director of Clinical Development, said:
"The Kahalalide F data confirm the excellent tolerability profile
reported in previous studies and establish that this compound class
warrants further clinical evaluation in combination to exploit its
therapeutic index. The promising activity observed with Aplidin(R) in
renal cancer and the fact that it is an inhibitor of the VEGF
pathway, which is known to be relevant in renal cancer, makes the
development of the compound in renal cancer a priority, particularly
in combination with established anti-angiogenic drugs in this type of
cancer. Aplidin remains in full development in solid and haematologic
tumours and in pediatric cancer.
"The latest data on Yondelis confirm its anti-tumour activity in
various sarcomas. They also demonstrate its potential as a
combination therapy with carboplatin and its possible use in a
variety of tumours where carboplatin is part of the standard
Notes to Editors
Kahalalide F is a depsipeptide derived from the sea slug Elysia
rufescens. Kahalalide F alters the function of the lysosomal
membranes inducing cell death by oncosis. Antitumour activity
independent of MDR (Multi Drug Resistance) and p53 status and to
correlate with basal ErbB3 expression.
Kahalalide F is currently in Phase II clinical trials in
hepatocellular carcinoma, non-small cell lung cancer (NSCLC) and
melanoma. It is also being evaluated for the treatment of severe
About Aplidin(R) (plitidepsin)
Aplidin(R) is a synthetic cyclodepsipeptide originally isolated
from the marine tunicate Aplidium albicans. The mechanism of action
of Aplidin(R) appears to involve oxidative mediated stress and is
still under investigation. Aplidin(R) induces rapid apoptosis and
also inhibits the VEGF (Vascular Entdothelial Growth Factor)
autocrine loop, crucial in the vascularisation and growth of tumours.
Human leukaemia and lymphoma tumour cell lines have been found to be
particularly sensitive to Aplidin in models resistant to standard
Phase II evaluation of Aplidin(R) in solid and haematological
malignancies is currently undergoing in Europe, the US and Canada. It
is also in Phase I in children with malignant solid tumours or
Aplidin has Orphan Drug designation from the EC and the FDA
for Acute Lymphoblastic Leukemia (ALL) and Multiple Myeloma (MM).
About Yondelis(R) (trabectedin)
Yondelis was originally isolated from the marine tunicate
Ecteinascidia turbinata. Yondelis has a distinct mechanism of action.
It is a unique antitumoural drug that binds into the minor groove of
the DNA and interacts with DNA repair enzymes and transcription
factors, interfering with cell cycle process. In July 2006,
Yondelis(R) was submitted to the European Medicines Agency (EMEA) for
regulatory approval for the treatment of soft tissue sarcomas (STS).
In addition to STS, Yondelis(R) is being studied in a pivotal Phase
III trial in ovarian cancer and in Phase II in prostate and breast
cancers. It was designated Orphan Drug status for STS and ovarian
cancer by the European Commission (E.C.) and the United States Food &
Drug Administration (U.S. FDA.)
Yondelis(R) is being developed by PharmaMar together with Johnson
& Johnson Pharmaceutical Research & Development, L.L.C. If key
studies are successful and support marketing approval, the agreement
between the parties provides that PharmaMar will market Yondelis(R)
in Europe while J&J companies, Ortho Biotech Products, L.P. and
Janssen-Cilag, will market the product in the U.S. and the rest of
the world respectively.
PharmaMar is the world's leading biopharmaceutical company in
advancing cancer care through the discovery and development of
innovative marine-derived medicines. PharmaMar's clinical portfolio
currently includes: Yondelis(R) (co-developed with J&JPRD) in Phase
III clinical trials; it was designated Orphan Drug status for soft
tissue sarcomas and ovarian cancer by the European Commission (E.C.)
and by the United States Food & Drug Administration (US FDA).
Aplidin(R), in Phase II, designated Orphan Drug for acute
lymphoblastic leukaemia and for multiple myeloma by the E.C. and by
the FDA; Kahalalide F in Phase II, and ES-285, Zalypsis(R) and
PM02734 in Phase I clinical trials.
PharmaMar, based in Madrid, Spain, is a subsidiary of the Zeltia
Group (Spanish stock exchange, ZEL).
For more information, contact:
Media: Lola Casals, PharmaMar Communication (tel.:
Investors: Catherine Moukheibir, Zeltia Capital Markets
Operations (tel.: +34-91-444-4500)
This press release is also available in the News section on
PharmaMar's web site: http://www.pharmamar.com/en/press/
ots Originaltext: PharmaMar
Im Internet recherchierbar: http://www.presseportal.ch
Media: Lola Casals, PharmaMar Communication (tel.: +34-91-846-6000);
Investors: Catherine Moukheibir, Zeltia Capital Markets Operations,