DGAP-News: Press Release: 4SC's Anti-Cancer Drug Resminostat achieves Median Overall Survival of 8.0 Months in Second-Line Advanced Liver Cancer (HCC) Patients
(firmenpresse) - DGAP-News: 4SC AG / Key word(s): Miscellaneous/Miscellaneous
Press Release: 4SC's Anti-Cancer Drug Resminostat achieves Median
Overall Survival of 8.0 Months in Second-Line Advanced Liver Cancer
(HCC) Patients
13.09.2012 / 07:34
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Press Release
4SC's Anti-Cancer Drug Resminostat achieves Median Overall Survival of 8.0
Months in Second-Line Advanced Liver Cancer (HCC) Patients
- Overall survival (OS) data from Phase II SHELTER trial in advanced
liver cancer (HCC)to be presented at 2012 ILCA Conference in Berlin,
Germany, on 16 September 2012
- Median OS of 8.0 months in resminostat/sorafenib combination group is
highest OS value to date in clinical trials in comparable second-line
HCC patient populations
- OS correlates with previously reported median progression-free-survival
of 4.7 months
- Innovative epigenetic mode of action (tumour re-sensitisation),
convincing signals of efficacy and favorable safety profile underline
further development of resminostat as a combination therapy with
sorafenib in first- and second-line advanced HCC
- Pivotal Phase III trial in second-line HCC planned to start by mid 2013
preferably with a partner
Planegg-Martinsried, Germany, 13 September 2012 - 4SC AG (Frankfurt, Prime
Standard: VSC), a discovery and development company of targeted small
molecule drugs for autoimmune diseases and cancer, announced today the
publication of convincing overall survival data from a Phase II study with
its lead anti-cancer drug resminostat applied as a novel combination
therapy approach with sorafenib in second-line advanced liver cancer at the
2012 annual meeting of the International Liver Cancer Association in
Berlin, Germany, on 16 September 2012.
The international, open-label, two-arm SHELTER study enrolled patients with
advanced liver cancer (hepatocellular carcinoma, HCC) who had shown proven
radiological tumor progression under first-line therapy with the cancer
drug sorafenib (Nexavar(R). The study investigated safety and efficacy of
resminostat as a monotherapy and in combination with sorafenib in this
patient group with currently no approved treatment option.
Final median overall survival (OS) of 8.0 months was determined in the
resminostat/sorafenib combination 'intend-to-treat' (ITT) population
(n=26), i.e. all study patients who were treated with the combination of
600 mg resminostat total daily dose (TDD) and 400 mg sorafenib TDD. In the
resminostat monotherapy group (ITT population, n=19), the final median OS
value has been determined as 4.1 months. All presented data are subject to
review upon database lock. In both study arms, resminostat has proven to be
safe and well tolerated. Notably, the overall health condition of the
patients enrolled in the SHELTER study was particularly severe (measured by
the clinical parameters ECOG status, BCLC stage and Child-Pugh class)
compared to other clinical studies with alternative investigational drugs
in second-line HCC patient populations.
To the Company's best knowledge, the 8.0 months median OS in the
resminostat/sorafenib combination group is the highest median OS value
achieved to date in clinical studies investigating the efficacy of new
treatment options for second-line advanced HCC in comparable patient
populations who have shown proven radiological tumour progression on
first-line sorafenib therapy. Moreover based on survival data reported from
the SHARP trial (which led to the approval of sorafenib), the survival
expectation of advanced HCC patients after developing progressive tumour
disease on this treatment is only 5.2 months.
There is a particular high medical need for the development of new
therapies for advanced HCC. To date, sorafenib is the only therapy approved
for the first-line treatment of advanced HCC. However, the median time to
tumour progression under sorafenib treatment has been reported to be 5.5
months (source: SHARP study). For these HCC patients who have shown
progressive disease on sorafenib there is no approved second-line treatment
available.
Resminostat progression-free survival (PFS) efficacy data of the SHELTER
study have been presented earlier this year at the Annual Meeting of the
American Society of Clinical Oncology (ASCO) on 4 June 2012 in Chicago
(USA). The data for the resminostat/sorafenib combination therapy showed a
progression-free survival rate (PFSR) after 12 weeks of treatment of 70.0%
and a median PFS of 4.7 months - one of the highest PFS figures recorded to
date by any second-line therapy in advanced clinical HCC studies. For the
resminostat monotherapy group, the final PFSR at 12 weeks is 35.3% and the
median PFS is 2.2 months. As previously reported, the primary study
endpoint PFSR at 12 weeks had been achieved ahead of schedule in both the
combination and the monotherapy group.
Professor Dr. Michael Bitzer, lead investigator of the SHELTER trial from
the Medical University Clinic in Tuebingen, Germany, will present the data
at the 6th Annual Conference of the International Liver Cancer Association
(ILCA) in Berlin, Germany (14-16 September 2012, www.ilca-online.org)
during an oral session on Sunday, 16 September 2012, from 10.30 am-12.00 pm
(CEST). The presentation will be available at
http://www.4sc.de/product-pipeline/publications-posters/resminostat when
the session begins at 10.30 am (CEST).
Dr. Ulrich Dauer, Chief Executive Officer of 4SC, commented: 'We are very
pleased with this study outcome. There is an enormous medical need in HCC
especially after several investigational drugs, mostly protein kinase
inhibitors, have recently failed in pivotal trials in this indication.
Resminostat, as a leading HDAC inhibitor in advanced clinical development,
offers a new and exciting therapeutic approach for advanced HCC: the use as
a combination drug with sorafenib both in first-line and second-line HCC.
We expect that the supplementary treatment with resminostat will restore or
significantly improve the efficacy of the administered sorafenib therapy. I
am confident that the impressive overall survival results from the SHELTER
trial will give us further momentum for the preparation of our planned
Phase III registration trial in combination with sorafenib in second-line
HCC which we intend to start, preferably together with a partner, by mid
2013.'
Dr. Bernd Hentsch, Chief Development Officer of 4SC AG, added: 'The median
overall survival value of 8.0 months in the resminostat/sorafenib
combination group represents a strong signal of efficacy and provides a
substantial clinical benefit for second-line HCC patients who otherwise
have no alternative treatment option. Importantly, these data show a
successful translation of the earlier reported median PFS of 4.7 months in
the combination group into an overall survival advantage. Moreover, these
data support the drug's innovative epigenetic mode of action: the
re-sensitising effect of resminostat towards HCC tumour cells which have
previously become tolerant and/or resistant to first-line sorafenib
treatment. The good safety and pharmacokinetic properties of resminostat as
well as the high 'combinability' due to the (re-) sensitising mode of
action offer great potential for resminostat as a combination therapy with
a broad range of chemotherapeutic and targeted therapies in numerous cancer
indications where drug tolerance and resistance is assumed to be modulated
by epigenetic mechanisms.'
Press Release Ends
Details of the Presentation:
Oral Presentation No.: O-030
Title: 'Efficacy, Tolerability and Pharmacokinetics of the Oral Histone
Deacetylase Inhibitor Resminostat in Patients with Advanced Hepatocellular
Carcinoma: Clinical Data from the Phase 2 Shelter Study'
Session title: General Session 5 - Clinical Trials (Oral Communication)
Session date and time: Sunday, 16 September 2012, 10:30 am-12:00 pm (CEST)
Authors/Presenters: M. Bitzer1, E.G. Giannini2, M. Horger3, U.M. Lauer1,
T.M. Ganten4, M.A. Woerns5, J.T. Siveke6, M.M. Dollinger7, G. Gerken8, M.E.
Scheulen8, H. Wege9, V. Zagonel10, U. Cillo11, F. Trevisani12, A.
Santoro13, V. Montesarchio14, A. Mais15, A. Ammendola15, T. Herz15, J.
Asche15, S. Henning15, B. Hauns15, B. Hentsch15, Shelter Study Group
1Medical University Clinic, Eberhard-Karls-University, Tuebingen, Germany,
2University Hospital, Genoa, Italy; 3Diagnostic Radiology,
Eberhard-Karls-University, Tuebingen, Germany; 4Department of Internal
Medicine, University of Heidelberg, Heidelberg, Germany; 5Medical
University Clinic, Mainz, Germany; 6Second Department of Internal Medicine,
Technical University, Munich, Germany; 7Department of Internal Medicine,
Martin Luther University, Halle, Germany; 8Department of Gastroenterology
and Hepatology, University of Duisburg-Essen, Essen, Germany; 9University
Hospital Hamburg-Eppendorf, Hamburg, Germany; 10Medical Oncology 1,
Istituto Oncologico Veneto - IRCCS, Padova, Italy; 11Hepatobiliary Surgery
and Liver Transplant Unit, Azienda Universitàdi Padova, Padova, Italy;
12University of Bologna, Bologna, Italy; 13Department of Oncology,
Humanitas Cancer Center, Rozzano, Italy; 14UO Oncologia Ospedale Cotugno
Napoli, Napoli, Italy; 154SC AG, Planegg-Martinsried, Germany
About the SHELTER Trial
The two-arm, international Phase II SHELTER study evaluates resminostat as
a second-line treatment of patients with advanced liver cancer (HCC), alone
or in combination with sorafenib (Nexavar(R)), the current standard of care
in the first-line treatment of advanced HCC, to see if it can prolong
progression-free survival (PFS) and overall survival (OS) in patients who
developed progressive disease under first-line treatment with sorafenib. In
the first study arm, patients are being treated with the recommended dose
of the combination therapy (600 mg resminostat and 400 mg sorafenib total
daily dose (TDD)) which was determined through an initial dose-escalation
part of the study. In the second study arm, patients receive resminostat as
monotherapy, administered orally, once daily, over five consecutive days,
followed by a nine day treatment-free period (5+9 dosing schedule). In the
combination arm, resminostat is administered in the same 5+9 dosing
schedule, while sorafenib is administered twice daily (BID) throughout the
cycle. In both study arms, this 14-day-cycle is repeated until there is
evidence of progressive disease or until the patient leaves the study for
other reasons. The first two radiological tumour assessments are performed
after six and 12 weeks; after that, tumour assessments are performed every
eight weeks. Patients who experience a clinical benefit, e.g. a
stabilization of their progressive disease or even a regression of the
tumour, may continue the study treatment. It was the primary study
objective to halt the further progression of this particularly aggressive
cancer disease in at least 20% of the patients treated and for at least 12
weeks in both therapy arms. The primary endpoint of the study is to
determine the progression free survival rate (PFSR) after these initial 12
weeks of treatment. Secondary endpoints include the analysis of
time-to-progression (TTP), progression-free survival time (PFS), overall
survival (OS), drug safetyand tolerability, pharmacokinetics and the
investigation of biomarkers.
About Liver Cancer (Hepatocellular Carcinoma, HCC)
Hepatocellular carcinoma (HCC) is the most frequent form of liver cancer.
Liver cancer is the fifth most common cancer worldwide and, with
approximately 700,000 deaths annually, the third most deadly. The incidence
of HCC is particularly high in Pacific-Asia and Southern Europe. The
aetiology of the disease varies between different areas. In Asia, hepatitis
B virus (HBV) infection is the major risk factor for HCC, whereas in the
Western world, hepatitis C virus (HCV) infection and alcohol abuse are the
most frequent cause for liver cirrhosis, and subsequently, HCC. Even though
over the past 10 years advancements in diagnosis and treatment of HCC have
lead to certain improvements in the prognosis for HCC patients, the
treatment options for patients with advanced HCC are still very poor. With
sorafenib (Nexavar(R)), there is currently only one compound approved for
this patient group. With a five-year survival rate of less than 10%,
advanced HCC has one of the lowest overall survival rates of all cancer
diseases worldwide. Thus, particularly for these patients with advanced
HCC, there is still a high unmet medical need for novel, systemic therapy
options, especially for patients refractory or intolerant to sorafenib.
About Resminostat
Resminostat (4SC-201), 4SC's lead oncology compound, is an oral
pan-histone-deacetylase (HDAC) inhibitor with an innovative epigenetic
mechanism of action that potentially enables the compound to be deployed as
a novel, targeted tumour therapy for a broad spectrum of oncological
indications, both as a monotherapy and in combination with other cancer
drugs. HDAC inhibitors have been shown to modify the DNA structure of
tumour cells to cause their differentiation and programmed cell death
(apoptosis) and are therefore considered to offer a mechanism of action
that has the particular potential to halt tumour progression and induce
tumour regression. Additionally, resminostat is also assumed to induce what
is known as tumour cell '(re-)sensitisation' to other anti-cancer
compounds. This process can suppress or reverse certain tolerance
mechanisms which tumour cells often develop against such cancer drugs.
Supplementary treatment with resminostat can be expected to restore or
significantly improve the efficacy of a previously administered cancer
therapy which was no longer effective; furthermore, combining resminostat
and common cancer drugs right from the very beginning can also be expected
to effectively enhance the success of such a treatment.
Resminostat is currently being investigated in a broad clinical Phase II
programme in the three indications liver cancer (hepatocellular carcinoma,
HCC), Hodgkin's Lymphoma (HL), and colorectal cancer (CRC). In the Phase II
SAPHIRE trial in patients with advanced Hodgkin's Lymphoma, resminostat in
monotherapy has demonstrated substantial anti-tumour activity, with an
overall response rate of 35.3% and a clinical benefit in 55.9% of the
patients in a heavily pre-treated patient population together with very
good safety and tolerability. In the Phase I/II SHORE study, which
evaluates resminostat in combination with the chemotherapeutic FOLFIRI
regimen as a second-line treatment of KRAS-mutant CRC patients, initial
results are expected in 2012. Furthermore, in the Phase II SHELTER study
resminostat is being evaluated as monotherapy and in combination with
sorafenib as a second-line treatment in advanced HCC after proven
radiological disease progression under first-line sorafenib therapy.
According to the data presented at the ASCO annual meeting on 4 June 2012,
resminostat/sorafenib combination therapy showed a progression-free
survival rate (PFSR) after 12 weeks of 70.0% and a median PFS of 4.7
months. The primary study endpoint has been achieved ahead of schedule in
both the combination and the monotherapy group.
4SC is currently in discussions with regulatory agencies and potential
partners in order to prepare a pivotal clinicalstudy programme for
resminostat in combination with sorafenib as a second-line treatment for
patients with advanced HCC who show tumour progression on first-line
treatment with sorafenib.
About 4SC
The Group managed by 4SC AG (ISIN DE0005753818) discovers and develops
targeted, small-molecule drugs for treating diseases with high unmet
medical needs in various autoimmune and cancer indications. These drugs are
intended to provide innovative treatment options that are more tolerable
and efficacious than existing therapies, and provide a better quality of
life. The Company's balanced pipeline comprises promising products that are
in various stages of clinical development. 4SC's aim is to generate future
growth and enhance its enterprise value by entering into partnerships with
leading pharmaceutical companies. Founded in 1997, 4SC had 90 employees at
30 June 2012. 4SC AG has been listed on the Prime Standard of the Frankfurt
Stock Exchange since December 2005.
Legal Note
This document may contain projections or estimates relating to plans and
objectives relating to our future operations, products, or services; future
financial results; or assumptions underlying or relating to any such
statements; each of which constitutes a forward-looking statement subject
to risks and uncertainties, many of which are beyond our control. Actual
results could differ materially, depending on a number of factors.
For more information please visit www.4sc.com or contact:
4SC AG
Jochen Orlowski, Corporate Communications&Investor Relations
jochen.orlowski(at)4sc.com, Tel.: +49 (0) 89 70 07 63 66
MC Services
Mareike Mohr, Raimund Gabriel
mareike.mohr(at)mc-services.eu, Tel.: +49 (0) 89 21 02 28 30
The Trout Group
Chad Rubin
Crubin(at)troutgroup.com, Tel.: +1 646 378 2947
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Company: 4SC AG
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E-mail: public(at)4sc.com
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