4SC AG / Key word(s): Miscellaneous
19.01.2012 08:23
Dissemination of an Ad hoc announcement according to § 15 WpHG, transmitted
by DGAP - a company of EquityStory AG.
The issuer is solely responsible for the content of this announcement.
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4SC's cancer compound resminostat meets primary endpoint in Phase II trial
in advanced liver cancer (HCC) ahead of schedule
- Clinical Phase II data to be presented at ASCO Gastrointestinal Cancer
Symposium
- Primary study endpoint met ahead of schedule both in mono and combination
therapy, based on advanced data set analysis
- Resminostat/sorafenib combination therapy halts further disease
progression in two thirds of patients (PFSR 66.6%) and achieves median
progression-free survival (PFS) of 4.6 months
- First successful clinical evaluation of resminostat's epigenetic mode of
action (resensitisation) in HCC therapy
- Company plans pivotal study programme
Planegg-Martinsried, Germany, 19 January 2012 - 4SC AG (Frankfurt, Prime
Standard: VSC), a discovery and development company of targeted small
molecule drugs for autoimmune diseases and cancer, today published
encouraging efficacy data from the clinical Phase II SHELTER study with the
cancer drug resminostat as a second-line therapy for patients with advanced
liver cancer (hepatocellular carcinoma, HCC) who had exhibited
radiologically proven tumour progression under first-line therapy with
sorafenib (Nexavar(R)) prior to study entry. This open-label, two-arm,
international study investigated the safety and efficacy of resminostat
both as a monotherapy and in combination with sorafenib for this difficult
to treat patient group, for which no approved treatment option is currently
available. According to the data now presented, which is based on an
advanced data set, the primary study endpoint of halting the further
progression of this particularly aggressive cancer in at least 20% of the
patients treated and for at least 12 weeks has been achieved ahead of
schedule in both therapy arms.
The trial's lead investigator, Prof. Dr. Michael Bitzer of Tübingen
University Hospital, will present the data on 20 January 2012 at 11:45 a.m.
PST (8:45 p.m. CET) as part of the 2012 ASCO Gastrointestinal Cancer
Symposium in San Francisco, CA in a poster, which is available as of now at
www.4sc.de/product-pipeline/publications-posters/resminostat.
The presentation will highlight that resminostat in combination with
sorafenib was able to prevent further progression of the disease for at
least 12 weeks in two-thirds of the currently 15 evaluable patients and
considerably longer - well over a year - in individual cases. Accordingly,
the progression-free survival rate (PFSR) after 12 weeks is currently 66.6%
for the combination therapy group and 33.3% for the monotherapy group of
currently 9 evaluable patients. Furthermore, median progression-free
survival (PFS), which is defined as the period of time for which the
progression of the disease can be halted, is presently 4.6 months (140
days) for the combination therapy group and 1.4 months (42 days) for the
monotherapy group.
In general, resminostat has proven to be safe and well-tolerated. The most
frequent side-effects observed were of a gastrointestinal nature
(diarrhoea, nausea). In the combination arm, in the majority of cases the
side effects were attributed to the treatment with sorafenib. The majority
of serious adverse events (SAEs) were attributed to the patient's
underlying disease; a consistent profile of SAEs which were causally
related to the study medication was not observed.
The data presented now were analysed before database closure and are based
on the analysis of the primary study endpoint 'progression-free survival at
12 weeks' conducted by the local trial centres. Currently, five patients
who have not been evaluated after 12 weeks yet are undergoing study
treatment, while another five patients continue treatment optionally after
experiencing a clinical benefit through the halt of disease progression for
at least 12 weeks of study participation. Patients withdrawing from the
trial for other reasons than disease progression are qualified as 'drop
outs' and therefore replaced. The final results of the SHELTER study, as
determined following database closure and encompassing all patients
enrolled as well as a final, centralised radiological report are expected
to be presented at an international scientific conference in the course of
2012.
Details of the efficacy data now presented based on the identification of
the primary study endpoint 'progression-free survival at 12 weeks':
Combination therapy (Resminostat 600 mg, Sorafenib 400 mg)
Patients enrolled ('intention-to-treat', ITT): 26
of which drop-outs*: 7
Currently evaluable patients after 12 weeks (EP)*: 15
of which with stable disease (SD), i.e. 'progression-free survival' (PFS):
10
of which with progressive disease (PD): 5
Progression-free survival rate after 12 weeks PFSR (=PFS/EP): 10/15= 66,6%
Monotherapy (Resminostat 600 mg)
Patients enrolled ('intention-to-treat', ITT): 12
of which drop-outs*: 2
Currently evaluable patients after 12 weeks (EP)*: 9
of which with stable disease (SD), i.e. 'progression-free survival' (PFS):
3
of which with progressive disease (PD): 6
Progression-free survival rate after 12 weeks PFSR (=PFS/EP): 10/15= 33,3%
*Patients who withdrew from the study before their tumour status was
determined radiologically after 12 weeks - and for whom an evaluation of
tumour progression or stabilisation was therefore not possible - have not
been included in the evaluable patient population (EP). Of the nine
patients listed as drop-outs most left the study for personal reasons (i.e.
withdrawal of consent), all of them without an observed tumour progression.
Early withdrawal because of side effects was a rare occurrence and only
partly attributable to the study medication.
Adhoc Ends
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Information and Explaination of the Issuer to this News:
Conference Call and Webcast
4SC will host a conference call and webcast on 19 January 2012 at 3pm CET
(9am EST) to inform about the data of the SHELTER study. Access to the
presentation slides can be obtained at:
http://4sc190112-live.cyber-presentation.de. Participants can access the
conference (conference ID: 4507526) under the following telephone numbers:
0800 10 12 072 (Germany)
0800 358 0886 (UK)
+1-877-941-1469 (USA)
+49 6103 485 3001 (other countries)
Details of the Presentation:
Presentation No / Abstract No: C26 / 262
Title: Investigation of the HDAC inhibitor resminostat in patients with
sorafenib-resistant hepatocellular carcinoma (HCC): Clinical data from the
phase I/II SHELTER study
Session date, time and location: Friday, 20 January 2012, 11.45 am
Californian time (PST), General Poster Session B: Cancers of the Pancreas,
Small Bowel, and Hepatobiliary Tract, Moscone West Building, 2012
Gastrointestinal Cancer Symposium, San Francisco, California
Presenters: M. Bitzer, M. Horger, T. Ganten, J. Siveke, M.A. Woerns, M.M.
Dollinger, V. Zagonel, U. Cillo, G. Gerken, M.E. Scheulen, H. Wege, E.
Giannini, V. Montesarchio, F. Trevisani, A. Mais, R. Jankowsky, B. Hauns,
B. Hentsch, U.M. Lauer
Increasing clinical relevance of epigenetically induced tumour cell
resensitisation
The now presented data of the SHELTER study validate in the view of the
company impressively the growing applicability of the new epigenetic
mechanism of action offered by 4SC's lead anti-cancer compound resminostat.
Tumour cell resensitisation, which is mediated by resminostat through the
inhibition of HDAC enzymes, is highly relevant for clinical practice, since
the supplementary administration of resminostat can permit the continued
and effective treatment of patients with a cancer drug to which patient
response is no longer adequate. In particular for patients suffering from
advanced liver cancer and who urgently need new treatment options it would
be a tremendous success to reduce the risk of disease progression. It is
therefore very promising that in the SHELTER study for two-thirds of
patients with advanced HCC, who no longer responded to sorafenib - the only
compound previously approved for this condition - the supplementary
administration of resminostat prevented the further disease progression for
at least 12 weeks and for much longer in individual cases. Resminostat also
showed promising activity as a monotherapy. In order to confirm these
encouraging and, as the company is convinced, clinically highly relevant
data, the company now planning to conduct a pivotal clinical study
programme relevant for registration in this indication and will therefore
intensify talks on this topic with the regulatory agencies and potential
partners.
Resminostat, 4SC's lead oncology compound, is an oral
pan-histone-deacetylase (HDAC) inhibitor with an innovative epigenetic
mechanism of action that enables this 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. By
causing structural changes to DNA, resminostat triggers a differentiation
in tumour cells, can induce programmed cell death in cancer cells
(apoptosis) and is able to halt tumour growth. Additionally, resminostat
induces what is known as tumour cell 'resensitisation' to the treatment
with other drugs. This resensitisation process can suppress or reverse drug
tolerance mechanisms that tumour cells often develop against other cancer
drugs and are catalysed by HDAC enzymes. Accordingly, supplementary
treatment with an HDAC inhibitor such as resminostat can thus restore - or
significantly improve - the efficacy of an initial cancer therapy. This
mechanism of action, i.e. tolerance breakdown via resensitisation through
HDAC inhibition, has previously been described in research1. The phase II
SHELTER trial is the first clinical study where this mechanism has been
investigated for the especially difficult to treat gastrointestinal
indication of advanced liver cancer (HCC) and documented for the
application of resminostat in combination with sorafenib, a tyrosine-kinase
inhibitor (TKI).
The principle of tumour cell resensitisation is highly relevant for
clinical practice, since the supplementary administration of resminostat
permits the continued treatment of patients with a cancer drug to which
patient response is no longer adequate. This can delay or avoid a change to
different cancer drugs - a procedure that is time-consuming and potentially
incriminating for the patient.
1 See Sharma et al., A chromatin-mediated reversible drug-tolerant state in
cancer cell subpopulations, Cell 2010;141(1):69-80.
About the SHELTER Trial Design
The two-arm, proof-of-concept, international Phase II SHELTER study
evaluates resminostat as a second-line treatment alone or in combination
with sorafenib (Nexavar(R)), the current standard of care in advanced HCC,
to see if it can prolong progression free survival (PFS) in patients who
prior to study entry developed progressive disease under first-line
treatment with sorafenib. In the first study arm, according to the study
protocol, at least 12 evaluable patients are being treated with the
recommended dose of the combination therapy (600 mg resminostat (OD) and
400 mg sorafenib (BID)) which was determined through an initial
dose-escalation part of the study. In the second study arm, at least 12
evaluable patients discontinue sorafenib treatment prior to inclusion and
then 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 daily
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 stagings are
performed after 6 and 12 weeks; after that, tumour stagings are performed
every eight weeks. Patients who experience a clinical benefit, e.g. a
stabilization of their progressive disease or tumour regression, may
continue the study treatment. It is the 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 12 weeks of treatment. Secondary endpoints include the
analysis of time-to-progression (TTP), progression free survival time
(PFS), overall survival (OS), drug safety and 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 condition. With a 5-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) is an oral pan-histone-deacetylase (HDAC) inhibitor.
HDAC inhibitors 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 also induces what is known as tumour cell 'resensitisation'.
This process can suppress or reverse tolerance mechanisms that tumour cells
often develop against other cancer drugs. Accordingly, supplementary
treatment with resminostat can thus restore - or significantly improve -
the efficacy of an initial cancer therapy. Resminostat is currently being
investigated in the Phase II SHELTER study as a second-line treatment for
advanced hepatocellular carcinoma (HCC) and in the Phase I/II SHORE study
as a second-line treatment in colorectal cancer (CRC) in KRAS-mutant
patients. Initial results of the SHORE study are expected in 2012. Moreover
resminostat is under evaluation in patients with advanced Hodgkin's
Lymphoma. In a first Phase II trial (SAPHIRE) in this indication
resminostat as a monotherapy has demonstrated, with an overall response
rate of 35.3% and a clinical benefit in 55.9% of the patients, substantial
anti-tumour activity in a heavily pre-treated patient population together
with very good safety and tolerability.
About 4SC AG
4SC (ISIN DE0005753818) discovers and develops targeted small-molecule
drugs for the treatment of diseases with a high unmet medical need in
various autoimmune and cancer indications. These drugs are intended to
provide patients with 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 currently has 94
employees and 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, Investor Relations & Public Relations
jochen.orlowski(at)4sc.com, Tel.: +49 (0) 89 70 07 63 66
Bettina v. Klitzing-Stückle, Corporate Communications
bettina.von.klitzing(at)4sc.com, Tel.: +49 (0) 89 70 07 63 0
MC Services
Raimund Gabriel
raimund.gabriel(at)mc-services.eu , Tel.: +49 (0) 89 21 02 28 30
Mareike Mohr
mareike.mohr(at)mc-services.eu, Tel.: +49 (0) 89 21 02 28 40
The Trout Group (USA)
Chad Rubin
Crubin(at)troutgroup.com, Tel.: +1 646 378 2947
19.01.2012 DGAP's Distribution Services include Regulatory Announcements,
Financial/Corporate News and Press Releases.
Media archive at www.dgap-medientreff.de and www.dgap.de
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Language: English
Company: 4SC AG
Am Klopferspitz 19a
82152 Martinsried
Germany
Phone: +49 (0)89 7007 63-0
Fax: +49 (0)89 7007 63-29
E-mail: public@4sc.com
Internet: www.4sc.de
ISIN: DE0005753818
WKN: 575381
Listed: Regulierter Markt in Frankfurt (Prime Standard); Freiverkehr
in Berlin, Düsseldorf, München, Stuttgart
End of Announcement DGAP News-Service
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DGAP-Adhoc: 4SC AG: 4SC's cancer compound resminostat meets primary endpoint in Phase II trial in advanced liver cancer (HCC) ahead of schedule
| Source: EQS Group AG