ABLYNX INITIATES A SINGLE AND MULTIPLE DOSE PHASE I STUDY OF CAPLACIZUMAB IN HEALTHY JAPANESE SUBJECTS
(Thomson Reuters ONE) -
* To assess the safety and tolerability of single and multiple doses of
caplacizumab in Japanese healthy volunteers
* To compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of
caplacizumab in Japanese and Caucasian subjects
* To evaluate the immunogenicity of caplacizumab in Japanese subjects
GHENT, Belgium, 26 June 2017 - Ablynx [Euronext Brussels: ABLX; OTC: ABYLY]
today announced that the first Japanese healthy volunteers have been dosed in
the Phase I single centre, randomised, double-blind, placebo-controlled study of
caplacizumab, its first-in-class anti-von Willebrand factor (vWF) Nanobody®
being developed for the treatment of acquired thrombotic thrombocytopenic
purpura (aTTP).
The goal of this Phase I study is to assess the safety, tolerability, PK and PD
profiles and immunogenicity of caplacizumab in healthy Japanese subjects, before
initiating studies in Japanese patients with aTTP. The study consists of single
ascending dose and multiple dose parts with blinded safety reviews prior to
proceeding to a higher dose or multiple dosing (NCT03172208). In total, 60
healthy Japanese and Caucasian subjects will be enrolled into the trial.
Dr Robert K. Zeldin, Chief Medical Officer at Ablynx, commented:
"The start of this Phase I study is an important step in making caplacizumab
available to Japanese patients suffering from aTTP. The study results are
expected to provide insights on the safety and dosing of caplacizumab in
Japanese subjects and enable bridging of data between Japanese and Caucasian
populations. We are looking forward to reporting the results of this study
before the end of 2017. This year, we will also report the top line results from
our Phase III HERCULES study in 145 patients with acquired TTP."
About caplacizumab
Caplacizumab is a bivalent anti-vWF Nanobody that received Orphan Drug
Designation in Europe and the United States in 2009. Caplacizumab blocks the
interaction of ultra-large vWF multimers (ULvWF) with platelets and, therefore,
has an immediate effect on platelet aggregation and the ensuing formation and
accumulation of the microclots that cause the severe thrombocytopenia, tissue
ischemia and organ dysfunction in aTTP. This immediate effect of caplacizumab
has the potential to protect the patient from the manifestations of the disease
while the underlying disease process resolves.
The efficacy and safety of caplacizumab in conjunction with the standard of care
of plasma exchange (PEX) and immunosuppression, were evaluated in the Phase II
TITAN study in 75 patients with aTTP. Caplacizumab was well-tolerated and the
primary endpoint was met (p=0.005), with caplacizumab treatment resulting in a
39% reduction in time to platelet count normalisation as compared to placebo
(i.e., a faster reversion of thrombocytopenia with consequent reduced use of
PEX)[1]. Moreover, during treatment, caplacizumab reduced recurrences of aTTP by
71% compared to placebo[2]. Post-hoc analyses of the Phase II TITAN study data
were performed to assess the impact of caplacizumab on a composite endpoint of
major thromboembolic complications and aTTP-related mortality, as well as on
refractoriness to standard treatment. The results demonstrate that a clinically
meaningful lower proportion of subjects treated with caplacizumab experienced
one or more major thromboembolic events, or died, as compared to placebo (11.4%
versus 43.2%)(2). In addition, fewer caplacizumab-treated patients, compared to
those who received placebo, were refractory to treatment (5.7% versus
21.6%)[3]. There were two deaths in the placebo group and both of those patients
were refractory to treatment; no deaths were reported in the caplacizumab group.
The randomised, double-blind, placebo-controlled Phase III HERCULES study
(NCT02553317) will evaluate the efficacy and safety of caplacizumab in patients
with aTTP when administered in addition to the standard-of-care. The primary
endpoint is time to platelet count normalisation, a measure of prevention of
further microvascular thrombosis. Key secondary endpoints include a composite
endpoint consisting of TTP-related mortality, recurrence of TTP and major
thromboembolic events during study drug treatment, as well as the prevention of
recurrence of TTP during the study period, refractoriness to treatment, and the
effect on biomarkers of organ damage. Results from this Phase III study are
expected in the second half of 2017 and these results are expected to support a
BLA filing in the United States in 2018. A Marketing Authorisation Application
(MAA) has already been submitted to the European Medicines Agency (EMA) for
approval of caplacizumab in aTTP[4]. If approved by regulatory authorities,
caplacizumab will be the first therapeutic specifically indicated for the
treatment of aTTP.
A three-year follow-up study (NCT02878603) of patients who have participated in
the HERCULES study is also in progress and will further evaluate the long-term
safety and efficacy of caplacizumab and repeated use of caplacizumab, as well as
characterizing the long-term impact of aTTP.
About aTTP
aTTP is a rare, acute, life-threatening, blood clotting disorder. It has a
sudden onset caused by impaired activity of the ADAMTS13 enzyme, leaving ULvWF
molecules uncleaved (vWF is an important protein involved in the blood clotting
process). These ULvWF molecules spontaneously bind to blood platelets, resulting
in severe thrombocytopenia (very low platelet count) and micro-clot formation in
small blood vessels throughout the body[5], leading to thrombotic complications
and widespread organ damage[6].
Despite the current standard-of-care treatment of PEX and immunosuppression,
episodes of aTTP are still associated with a mortality rate of up to 20%, with
most deaths occurring within 30 days of diagnosis[7]. Furthermore, patients are
at risk of acute thromboembolic complications (e.g. stroke, myocardial
infarction) and of recurrence of disease. Some patients are refractory to
therapy(3), which is associated with a poor prognosis for survival of an acute
episode of aTTP. Long term, patients are at increased risk of hypertension,
major depression, and premature death[8].
About Ablynx
Ablynx is a biopharmaceutical company engaged in the development of Nanobodies,
proprietary therapeutic proteins based on single-domain antibody fragments,
which combine the advantages of conventional antibody drugs with some of the
features of small-molecule drugs. Ablynx is dedicated to creating new medicines
which will make a real difference to society. Today, the Company has more than
45 proprietary and partnered programmes in development in various therapeutic
areas including inflammation, haematology, immuno-oncology, oncology and
respiratory disease. The Company has collaborations with multiple pharmaceutical
companies including AbbVie; Boehringer Ingelheim; Eddingpharm; Merck & Co.,
Inc., Kenilworth, New Jersey, USA; Merck KGaA; Novartis; Novo Nordisk and Taisho
Pharmaceuticals. The Company is headquartered in Ghent, Belgium. More
information can be found on www.ablynx.com.
For more information, please contact
Ablynx:
Dr Edwin Moses
CEO
t: +32 (0)9 262 00 07
m: +32 (0)473 39 50 68
e: edwin.moses(at)ablynx.com
Lies Vanneste
Director Investor Relations
t: +32 (0)9 262 01 37
m: +32 (0)498 05 35 79
e: lies.vanneste(at)ablynx.com
Follow us on Twitter (at)AblynxABLX
Ablynx media/analyst relations
FTI Consulting:
Julia Phillips, Brett Pollard, Mo Noonan
t: +44 20 3727 1000
e: ablynx(at)fticonsulting.com
--------------------------------------------------------------------------------
[1] Press release June 2014; Manuscript in the NEJM, Feb 2016; Manuscript in the
JTH, Apr 2017
[2] Peyvandi et al., notes to editor NEJM 2016
[3] Defined as: 'failure of platelet response after 7 days despite daily plasma
exchange treatment'
[4] Press release February 2017
[5] Veyradier, NEJM 2016: "von Willebrand Factor - A new target for TTP
treatment?"
[6] Scully et al., Br J Hem 2012; Sarode et al., J Clin Apher 2014; Chaturvedi
et al., Am J Hem 2013
[7] Benhamou, Y. et al., Haematologica 2012
[8] Deford et al., Blood 2013
pdf version of the press release:
http://hugin.info/137912/R/2115371/804942.pdf
This announcement is distributed by Nasdaq Corporate Solutions on behalf of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely responsible for the content, accuracy and originality of the information contained therein.
Source: Ablynx via GlobeNewswire
Unternehmensinformation / Kurzprofil:
Datum: 26.06.2017 - 07:00 Uhr
Sprache: Deutsch
News-ID 549666
Anzahl Zeichen: 9888
contact information:
Town:
Ghent/Zwijnaarde
Kategorie:
Business News
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