Transgene S.A. (Paris:TNG) (Euronext Paris : FR0005175080) announces
today the presentation, during the EASL (European Association for the
Study of Liver) congress in Barcelona, Spain, of follow up interim
data showing both a more rapid response as well as an improved long term
effect on viral load decrease in a combination of TG4040 with PEG-IFN?
(pegylated interferon alpha) and ribavirin (the current
standard of care) in patients chronically infected with genotype 1
hepatitis C virus.
These data were observed in a randomized phase 2 trial that has enrolled
153 patients (the "HCVac" study). HCVac had three treatment arms: one
control arm (Arm A) with the current standard of care alone and two arms
(B and C) with a combination of this standard of care and TG4040
delivered in two different administration schedules, including one
schedule (Arm C) with pre-vaccination by TG4040 (i.e. TG4040 injected
prior to the introduction of PEG-IFN? and ribavirin).
As reported in November 2011 at the AASLD meeting in San Francisco, the
primary endpoint of the HCVac study was met in the pre-vaccination arm C
with 64% (34/53) evaluable patients having achieved a complete early
viral response1 ("cEVR") at week-12 after initiation of
treatment with the standard of care compared to 30% (9/30) in the
control arm A (p=0.003).
The positive effect of TG4040 pre-vaccination was observed as early as
one week after initiation of treatment with the standard of care: the
slope of mean viral load decrease was significantly steeper in Arm C
(1.4 log10 IU/ml) compared to Arms A and B (respectively 0.9 and 1.0
log10 IU/ml) (p=0.04), meaning a faster viral response in Arm C than in
When following the viral response at week-24 after the initiation of
treatment with the standard of care in the patients evaluable for cEVR
(week-12), the responses continue to improve as expected in all arms:
70% in the control Arm A, 67% in the Arm B (initiation of treatment with
the standard of care before introduction of TG4040) and 79% (vs. 64% at
week-12) in the Arm C.
Preliminary End-of-Treatment Response measurement ("ETR", or viral
response measured at the end of 48 weeks of standard of care), is
respectively 64% and 56% in Arm A and B. In arm C, 19 out of 19 patients
analysed so far are undetectable.
"These data are important for TG4040 as they confirm the efficacy
profile of our therapeutic vaccine. As far as we know, they are unheard
of for an immunotherapy in HCV and this is one of the reasons why we
were invited for a late breaker oral presentation in such a prestigious
event" said Philippe Archinard, Chairman and CEO of Transgene. He
added: "The benefit seen at week-12 in the pre-vaccination arm is
further confirmed at week-24 and the preliminary data of ETR in this arm
are also very encouraging".
Data were presented on Saturday April, 21, at the annual meeting of the
European Association for the Study of Liver (EASL) in Barcelona, by Pr.
Heiner Wedemeyer, MD, of the Department of Gastroenterology, Hepatology
and Endocrinology at Hannover Medical School (Germany) and principal
investigator of the HCVac study.
Pr. Wedemeyer said: "The data accumulated so far in the HCVac study
illustrate the importance of immunity in the treatment of chronic
hepatitis C". He added: "The assessment of TG4040 in a
combination with directly acting agents (DAA) should be the next
Transgene's TG4040 vaccine candidate is a recombinant vector based on
the MVA virus carrying and expressing three of the major non-structural
proteins (NS3, NS4 and NS5B) of the hepatitis C virus ("HCV"). The MVA
vector is a highly attenuated strain of vaccinia virus, which has been
tested extensively in humans as a vaccine against smallpox and is known
to strongly stimulate innate and adaptive immune responses to antigens.
About TG4040 clinical development program:
Phase 1 clinical results in 39 treatment naïve genotype 1 HCV patients
showed that the product is safe and well tolerated at all dose levels
tested. Immunological analyses on 15 treatment naïve patients were
encouraging and supported the expected mechanism of action of TG4040
which aims at inducing an effective HCV-specific T cell based immune
response, able to control viral replication. Phase 1 data were published
in the journal Gastroenterology and reported in Nature Reviews
153 patients in the HCVac study were recruited in five countries in
Europe, in the United States and in Israel, and were randomized in one
control arm (Arm A) or one of the two experimental arms (Arms B and C).
In the Arm B, the TG4040 dosage was administered 6 times and the
standard of care was given 4 weeks prior to the initiation of TG4040. In
the Arm C, the TG4040 dosage was administered 13 times and the standard
of care was introduced 12 weeks after the initiation of treatment with
TG4040. The HCVac study is investigating the efficacy and safety of two
different schedules of administration of TG4040 administered in
subcutaneous injections at the dose of 107 pfu in combination
with Peg-IFN and RBV.
The three cases of severe haematological adverse events, one aplastic
anemia and two cases of thrombocytopenia, reported in October 2011, all
recovered within 1 to 4 months. A fourth case corresponding to a
thrombocytopenia was recorded recently. Of interest, the three cases of
thrombocytopenia share all a same class 2 Human Leukocyte Antigen
("HLA") allele. This association is statistically significant and, as
these HLA types could be excluded a priori in a new clinical
trial, this will be taken into account in future developments of the
therapeutic vaccine, should it be combined with standard of care
including PEG-IFN?. These adverse events should also have no impact in
future developments without PEG-IFN?.
About chronic hepatitis C:
Hepatitis C currently represents a major public health concern. The
population chronically infected with HCV in the world is estimated at
170 to 200 million and hepatitis-C-related deaths at approximately
470,000 annually. Peak of prevalence of HCV-related diseases is expected
to occur in 2025-2030 in developed countries.
HCV infection leads to liver diseases such as fibrosis, cirrhosis and
liver carcinoma, which are the prime indications for liver transplants.
The commonly used treatment regimen for patients infected with the HCV
genotype 1 (a combination of Pegylated Interferon ? and Ribavirin) is
lengthy, often poorly tolerated and effective in only approximately 50%
of patients completing therapy. In addition, a substantial number of
patients never receive therapy. Therefore, there is a strong medical
need for new alternative approaches, including combination therapies.
Transgene, a member of the Institut Mérieux Group, is a publicly traded
French biopharmaceutical company dedicated to the development of
therapeutic vaccines and immunotherapeutic products in oncology and
infectious diseases and has four compounds in phase 2 clinical
development: TG4010 and JX594/TG6006 having already completed initial
phase 2 trials, TG4001 and TG4040. Transgene has concluded strategic
agreements for the development of two of its immunotherapy products: an
option agreement with Novartis for the development of TG4010 to treat
various cancers and an in-licensing agreement with US-based Jennerex,
Inc. to develop and market JX594/TG6006, an oncolytic virus. Transgene
has bio-manufacturing capacities for viral-based products. Additional
information about Transgene is available at transgene.fr.
This press release contains certain forward-looking statements.
Although the company believes its expectations are based on reasonable
assumptions, these forward-looking statements are subject to numerous
risks and uncertainties, which could cause actual results to differ
materially from those anticipated. In particular, the Company's ability
to commercialize its first product depends on the continuing success of
clinical studies, ongoing financing for further product developments and
marketing launch, a positive response from the medical community
regarding the product's costs and effectiveness. For a discussion of
risks and uncertainties which could cause the company's actual results,
financial condition, performance or achievements to differ from those
contained in the forward-looking statements, please refer to the Risk
Factors ("Facteurs de Risque") section of the Document de Reference
prospectus, which is available on the AMF website (http://www.amf-france.org)
or on Transgene's website (www.transgene.fr).
This press release and the information contained herein do not
constitute an offer to sell or a solicitation of an offer to buy or
subscribe to shares in Transgene in any country.
1 Limit of detection for the HCV RNA quantification test:
Philippe Archinard, CEO
Phone: +33 (0)3 88 27
Stéphane Boissel, Executive Vice President & CFO
+33 (0)3 88 27 91 02
Elisabetta Castelli, Director IR
+33 (0)1 44 08 55 05
+49 89 210 228 30
Phone: +44 207 148 5998