DGAP-News: 4SC AG / Key word(s): Miscellaneous
4SC's Resminostat Meets Primary Efficacy Endpoint in Phase II Trial in
Hodgkin's Lymphoma (HL)
06.09.2011 / 07:45
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- Resminostat shows substantial clinical benefit in heavily pre-treated
relapsed/refractory HL Patients -
Planegg-Martinsried, Germany, 6 September, 2011 - 4SC AG (Frankfurt, Prime
Standard: VSC), a discovery and development company of targeted small
molecule drugs for autoimmune diseases and cancer, today announced positive
topline data from its Phase II SAPHIRE trial with resminostat, its oral pan
HDAC inhibitor, in patients with relapsed/refractory Hodgkin's Lymphoma
(HL). Resminostat monotherapy exhibited substantial anti-tumour activity,
including complete and partial tumour responses. Analysis of tumour
response assessments revealed that the study achieved its primary endpoint.
Furthermore the study verified the drug to be safe and well tolerated in
this advanced stage patient population.
In June 2011 the SAPHIRE trial completed patient enrolment. 33 patients
have been evaluated for tumour response which, according to the study
protocol, represents the targeted number of patients required for efficacy
analyses. Central assessment of patient tumour data by an independent
expert review board revealed objective tumour responses in 11 patients,
constituting a 33.3% overall response rate (ORR) and thereby successfully
achieving the pre-defined requirements of the primary endpoint of the
study. This ORR of 33.3% together with a clinical benefit recorded in total
for 54.5% of the patients (disease control rate) demonstrates the
substantial anti-tumour activity of resminostat monotherapy in an advanced
and heavily pre-treated Hodgkin's Lymphoma patient population for which
there is currently no established standard therapy available. Prior to
study entry, the patients enrolled received a median of 6 treatments
consisting of various chemo- and radiation therapies including autologous
stem cell transplantation in 57% of the cases.
The clinical activity of resminostat was measured through PET/CT, the
combination of positron-emission tomography (PET) and computer tomography
(CT). Study responders included 1 complete response (CR) and 3 partial
responses (PR) according to Cheson criteria [1]. Furthermore, 7 patients
experienced partial metabolic responses (PMR) according to EORTC criteria
[2]. An additional 7 patients achieved stabilization of their disease.
Thus, in total 18 of 33 patients, representing 54.5% of all patients
evaluated for efficacy, received a clinical benefit from resminostat
treatment. Additional two patients are currently continuing on study
therapy in the optional follow-up phase, and have therefore not been
subject to final response evaluation by the independent review board.
Treatment with resminostat was generally well tolerated with common grade
2-3 adverse events [3] mainly being of gastrointestinal (nausea) or
hematological (anemia, thrombocytopenia) origin. All adverse events were
well manageable by dose modification or symptomatic treatment. Assessment
of pharmacokinetic (PK) parameters confirmed the favorable profile of the
oral administration route and dose dependent resminostat plasma
concentrations.
'We are very encouraged by the results from this trial in a very heavily
pre-treated patient population. With an overall response rate of 33.3% and
with more than half of the patients experiencing a clinical benefit
resminostat could become a novel therapy in Hodgkin's Lymphoma,' said
Ulrich Dauer, Chief Executive Officer of 4SC. 'This excellent efficacy data
in patients with no further established treatment options combined with the
very positive safety profile of resminostat provides us with the
information we need to initiate the next development steps for this
compound. We intend to discuss the path towards registration with the
regulatory agencies in the near future.'
Final data from this trial, including secondary endpoints, will be
presented at an upcoming international scientific conference.
Ends
About the SAPHIRE Trial Design
The SAPHIRE trial included HL patients that had relapsed after high dose
chemotherapy and/or autologous stem cell transplantation (ASCT) or had
become refractory to treatment. The study was designed as an open-label,
single-arm, international trial consisting of two recruitment stages
according to the Simon's Minimax design. Resminostat has been administered
orally at a once daily dose of 600 mg during the 1st recruitment stage and
due to its good tolerability at a higher daily dose of 800 mg in the 2nd
stage. Patients were treated in 14-day cycles of five consecutive days
followed by a nine-day treatment-free period (5+9 schedule). Patients
underwent assessment of their disease status by computed tomography in
combination with positron emission tomography (PET/CT) after Cycle 3 and
Cycle 6 and thereafter every fourth cycle during an optional follow-up
period in which patients could continue treatment until disease
progression. The primary endpoint of the study was defined as the overall
objective response rate (ORR) based on the best objective response during
treatment. Secondary endpoints include time to response (TTR), duration of
response (DOR), progression free survival (PFS), overall survival (OS),
safety and tolerability and the evaluation of drug regulated biomarkers
including the assessment of TARC levels.
About Hodgkin's Lymphoma
Hodgkin's Lymphoma (HL) is a cancer of the lymphatic system, which is part
of the immune system, and leads to the abnormal growth of lymphatic cells
that compromise the immune system's ability to fight infection and may even
spread beyond the lymphatic systems to other organs. Typical symptoms of HL
include the painless swellings of the lymph nodes, spleen or other tissue
and an overall impairment of the hematopoietic system, as well as fever,
weight loss or night sweats. The main causes for the development of HL are
still unknown. Recent research shows that this cancer has its origin from a
degenerated lymphatic cell, the B lymphocyte.
HL is a curable malignant lymphoma in the majority of cases. However, not
all patients can be cured and available therapies for this disease can have
significant long-term toxicity. The incidence of HL in 2008 was 11,777 new
cases in Europe and 8,220 new cases in the US. The age distribution is
bimodal; the first peak occurs between the ages of 15 and 30 years and the
second in the sixth decade.
Therapy options for HL patients depend on the stage of the disease and
number and regions of lymph nodes affected. The first treatment line for
HL, after the initial diagnosis, consists of chemotherapy and/or radiation,
achieving cure rates of up to 80%. Standard of care for patients with
refractory or relapsing disease after initial therapy comprises salvage
chemotherapy followed by high-dose chemotherapy and autologous stem cell
transplantation. Patients relapsing after second line therapy have a 5-year
overall survival rate of only 17% [4]. Since there is no standard of care
in patients with resistant/refractory HL, there is an especially high need
to develop novel therapies for these patients.
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. Resminostat is
currently being investigated in the Phase II SHELTER study as a second-line
treatment for advanced hepatocellular carcinoma and in the Phase I/II SHORE
study as a second-line treatment in colorectal cancer in KRAS-mutant
patients. The SHELTER study is expected to report Phase II results in 2011.
Initial results of the SHORE study are expected in 2012.
The reported Phase II SAPHIRE trial for resminostat as a third-line therapy
in Hodgkin's lymphoma is still ongoing as two patients are continuing on
study therapy in the optional follow-up phase beyond 12 weeks of treatment.
Resminostat is currently partnered in Japan with Yakult Honsha.
Conference Call & Webcast
The senior management team of 4SC will host a conference call and webcast
at 3pm CET (9am EST) today to inform about the topline results of the
SAPHIRE study.
Access to the presentation slides can be obtained at:
http://4sc060911-live.cyber-presentation.de
Participants can access the conference under the following telephone
numbers:
Date: 6 September, 2011
Time: 3pm CET (9am EST)
Dial-in numbers:
0800 10 12 072 (Germany)
0800 358 0886 (UK)
1 877 941 1469 (USA)
+49 (0) 6103 485 3001 (other countries)
Conference-ID: 4470246
Approximately two hours after the live presentation, an audio replay will
be available on the 'investors' section of the homepage www.4sc.com.
About 4SC
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.
References
[1] Revised Response Criteria for Malignant Lymphoma (Cheson et al., JCO,
2007)
[2] EORTC Criteria (Young et al., EJC, 1999)
[3] CTCAE version 4
[4] Long-term outcome of ASCT in relapsed or refractory HL (Sirohi et al.,
Ann.Oncol., 2008)
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 further information, please visit www.4sc.com or contact:
4SC AG
Jochen Orlowski, Investor Relations & Public Relations
jochen.orlowski@4sc.com
Tel.: +49 (0) 89 70 07 63 0
Bettina v. Klitzing-Stückle, Corporate Communications
bettina.von.klitzing@4sc.com
Tel.: +49 (0) 89 70 07 63 0
MC Services (Europe)
Raimund Gabriel
raimund.gabriel@mc-services.eu
Tel.: +49 (0) 89 21 02 28 30
The Trout Group (USA)
Chad Rubin
Crubin@troutgroup.com
Tel.: +1 646 378 2947
End of Corporate News
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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 News DGAP News-Service
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138256 06.09.2011
DGAP-News: 4SC's Resminostat Meets Primary Efficacy Endpoint in Phase II Trial in Hodgkin's Lymphoma (HL)
| Source: EQS Group AG