MOLOGEN AG Announces Top Line Data of Pivotal IMPALA Study in Metastatic Colorectal Cancer
05 August 2019 - 7:42PM
Business Wire
- Primary endpoint not met: median overall survival of 22
months in lefitolimod group compared to 21.9 months in control
group; p=0.2765; hazard ratio HR: 1.12 (95% CI: 0.91 -
1.38)
- No new safety signals detected
- Future focus on combination approaches for both lefitolimod
and the first clinical candidate from the EnanDIM® family
The biopharmaceutical company MOLOGEN AG (ISIN DE000A2LQ900,
SIN A2L Q90) announced today the top line data of its pivotal phase
III IMPALA study. The study compares the TLR9 agonist lefitolimod
(MGN1703) with local standard of care as a maintenance therapy in
patients with metastatic colorectal cancer presenting with an
objective tumor response following first-line induction therapy.
The primary endpoint – overall survival (OS) – was not met showing
a median OS of 22.0 and 21.9 months in the lefitolimod and control
group respectively (p=0.2765; HR=1.12; 95% CI 0.91 - 1.38).
Timepoint related OS and predefined sub-group analyses did also not
indicate a benefit, while regarding Progression Free Survival (PFS)
standard of care was superior to lefitolimod treatment. No new
safety signals were detected; hence the favorable safety and
tolerability profile was confirmed.
MOLOGEN is a pioneer in the field of immunotherapy, especially
in the TLR9 field with the product family of DNA-based TLR9
agonists including its lead compound lefitolimod, as well as its
follow-up molecules EnanDIM®. Given its mode of action and
confirmed favorable safety profile, lefitolimod is being used as
combination partner in anti-cancer and anti-HIV
immunotherapies.
Dr med Stefan M. Manth, CEO of MOLOGEN, noted: “We are
disappointed with these top-line results and will now analyze the
bountiful data coming out of IMPALA in depth. We will then build on
these analyses from IMPALA to further inform the development of
lefitolimod and its successor molecules from the EnanDIM® platform
for cancer and HIV patients. We are grateful to the patients and
investigators for their participation in this important study.”
Dr med Matthias Baumann, CMO of MOLOGEN, stated: “Unfortunately
the positive results in our single agent lefitolimod phase II
IMPACT study did not translate into a successful outcome of our
phase III IMPALA trial despite the fact that all learnings have
been incorporated into the trial design. In contrast to the time
when the IMPALA design was conceived, it now appears that for
successful anti-cancer immunotherapies a combination approach is of
paramount importance. Due to the large body of evidence indicating
the potential of TLR9 agonism in this context we remain committed
to the further development of our candidates.”
The detailed data from this first top line analysis of the
IMPALA trial will be submitted for presentation at an upcoming
international scientific congress.
Strategic focus on combination therapies in indications with
high medical need and significant market potential
In light of these results the strategy of MOLOGEN going forward
will focus on combination approaches for both lefitolimod and the
first clinical candidate from the EnanDIM® family in ongoing and
planned clinical trials. This strategy serves as cornerstone for
ongoing licensing and funding efforts.
Further to the IMPALA single-agent approach, lefitolimod is
currently being evaluated in a phase I/II clinical study in
combination with the checkpoint inhibitor Yervoy® (ipilimumab) in a
broader variety of solid tumors. The study is being conducted at
the renowned MD Anderson Cancer Center, Texas, USA. In addition to
studies in the field of oncology, lefitolimod has also been tested
in HIV patients in a phase Ib/IIa study, the TEACH trial. Based on
the encouraging study results, lefitolimod will be investigated in
a phase IIa combination study, the TITAN trial, in HIV-infected
patients in combination with innovative virus-neutralizing
antibodies developed by the Rockefeller University in New York,
USA. The trial will be conducted in cooperation with the Aarhus
University Hospital in Denmark, which was also the academic partner
of MOLOGEN in the TEACH trial. TITAN is funded by the US biotech
company Gilead Inc. Furthermore, plans for another clinical
combination study in HIV with a prominent US center are at an
advanced stage.
The next generation TLR9 agonistic molecules of the
EnanDIM®-family coming out of the research labs of MOLOGEN offer
additional potential for development in various cancer indications
and HIV. A first clinical candidate from the EnanDIM® platform is
presently in late pre-clinical testing and expected to launch into
clinical development in oncology at the end of 2019.
Checkpoint inhibitors alone are expected to generate sales of
approximately US$ 25 billion by 2022 (acc. to Research and Markets)
in a growing variety of indications. However, the greatest
potential of checkpoint inhibitors is still to be realized, i.e.
with adequate combination partners to target indications
non-amenable to checkpoint inhibitor monotherapy. Estimates from
the market research organization Research and Markets project that
the market for cancer immunotherapies could rise to more than
US$100 billion by 2024.
Background to the IMPALA study
IMPALA (Immunomodulatory MGN1703 in
Patients with Advanced Colorectal
Carcinoma with tumor reduction during induction treatment)
is a pivotal, randomized, international, multicenter, open-label
phase III trial. The study involves more than 540 patients from
eight European countries, including the five major European
pharmaceutical markets. Recruitment was completed in May 2017. The
study includes patients with metastatic colorectal cancer who have
responded to standard first-line treatment. Lefitolimod is
subsequently administered subcutaneously 60 mg twice weekly as
maintenance therapy. The primary endpoint is overall survival and
secondary study endpoints include progression-free survival, safety
and tolerability, as well as Quality of Life (QoL).
The study is conducted in collaboration with three highly
profiled national collaborative study groups: Arbeitsgemeinschaft
Internistische Onkologie (AIO) in Germany, Grupo Español de
Tratamiento de Tumores Digestivos (TTD) in Spain and Groupe
Coopérateur Multidisciplinaire en Oncologie (GERCOR) in France.
For more information on IMPALA please visit
www.clinicaltrials.gov.
MOLOGEN AG
MOLOGEN AG is a German biopharmaceutical Company and a pioneer
in the field of immunotherapy on account of its unique active
agents and technologies. Alongside a focus on immuno-oncology,
MOLOGEN develops immunotherapies for the treatment of HIV and
infectious diseases.
The focus of MOLOGEN’s development is on DNA-based TLR9
agonists, where it has consistently been ahead of the course. This
includes the lead compound, the immunotherapy lefitolimod, and its
next generation molecules EnanDIM®, building the foundation for a
next generation immunotherapy platform in areas of unmet need.
Forthcoming milestones include: the start of the TITAN study in
HIV, the start of the clinical development of EnanDIM® and
additional combination studies in cancer, including one with our
strategic partner Oncologie Inc., which are in an advanced planning
stage.
MOLOGEN AG is a publicly listed Company, headquartered in
Berlin. The shares (ISIN, DE000A2LQ900/SIN: A2L Q90) are listed in
the Prime Standard of the German Stock Exchange.
www.mologen.com
Disclaimer
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affairs on the day of publication.
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Claudia Nickolaus Head of Investor Relations &
Corporate Communications Tel: +49 - 30 - 84 17 88 - 37 Fax: +49 -
30 - 84 17 88 - 50 investor@mologen.com