mardi 7 juillet 2020

Chugai’s Bispecific Antibody Emicizumab Meets Primary Endpoint in Phase lll Study

Par Rédaction , dans Communiqués , le 20 novembre 2017

Monday, November 20th 2017 at 8:29am UTC

– emicizumab prophylaxis shown to reduce bleeding in patients without
inhibitors –

Pharmaceutical Co., Ltd.
(TOKYO:4519) announced today that the
primary endpoint has been met for the global phase lll HAVEN 3
(NCT02847637) study evaluating emicizumab (ACE910) subcutaneous
injection, once a week and once every two weeks, in patients with
hemophilia A (12 years of age or older) without inhibitors to factor
Vlll. A statistically significant reduction in the number of bleeds was
confirmed in patients treated with emicizumab prophylaxis compared to
those receiving no prophylactic treatment. The study also met a
secondary endpoint that once-weekly emicizumab prophylaxis was superior
to factor VIII prophylaxis, as demonstrated by a statistically
significant and clinically meaningful reduction in treated bleeds in an
intra-patient comparison of patients receiving emicizumab prophylaxis
compared to their prior factor VIII prophylaxis. The most common adverse
events with emicizumab were injection site reactions, consistent with
prior studies. No thrombotic events occurred in this study. Further
details will be presented at a future medical meeting.

“Prophylactic factor VIII replacement therapy is a standard treatment
for hemophilia A patients without inhibitors. However, some patients and
their caregivers have difficulties with the frequent intravenous
injections in their daily life,” said Chugai’s Senior Vice President,
Head of Project & Lifecycle Management Unit, Dr. Yasushi Ito. “As a
subcutaneous injection, emicizumab can be administered more easily.
Today’s results, which are consistent with data reported from patients
with inhibitors earlier this year, showed that emicizumab may have the
potential to become an efficacious treatment option for hemophilia A
patients without inhibitors. We expect emicizumab to provide benefits to
a wide range of patients with hemophilia A.”

Emicizumab is an investigational bispecific monoclonal antibody, which
was developed using Chugai’s proprietary antibody engineering
technologies. The drug is designed to bind factor lXa and factor X. In
doing so, emicizumab provides the cofactor function of factor Vlll in
people with hemophilia A, who either lack or have impaired coagulation
function of factor Vlll1,2). In November this year, the drug
(US product name: HEMLIBRA®; Genentech) was approved by the
U.S. Food and Drug Administration “for routine prophylaxis to prevent or
reduce the frequency of bleeding episodes in adult and pediatric
patients with hemophilia A (congenital factor VIII deficiency) with
factor VIII inhibitors”. An EU marketing authorization application was
submitted in June 2017 and is being reviewed under Accelerated
Assessment by the European Medicines Agency. In Japan, emicizumab
obtained an orphan drug designation in August 2016 from the Ministry of
Health, Labour and Welfare for the prevention and reduction of bleeding
episodes in patients with congenital FVIIl deficiency (hemophilia A) who
developed inhibitors to FVIII, followed by an application for regulatory
approval filed in July 2017.

About HAVEN 3 study (NCT02847637)

HAVEN 3 study is a randomized, multicentre, open-label phase lll study
evaluating the efficacy, safety and pharmacokinetics of emicizumab
prophylaxis subcutaneous injection once a week and once every two weeks.
The study enrolled 152 patients with hemophilia A, 12 years of age or
older without inhibitors to factor Vlll, who were previously treated
with episodic or prophylactic factor Vlll therapy. The primary endpoint
of the study is the number of bleeds over time with emicizumab
prophylaxis (Arm A and Arm B) versus no prophylaxis (Arm C). Secondary
endpoints include joint bleed rate, target joint bleed rate,
health-related quality of life (HRQoL)/ health status, intra-patient
comparison to bleed rate on their prior prophylaxis regimen with factor
Vlll therapy (Arm D) and safety.


[Study Design]

Patients previously treated with episodic factor Vlll therapy were
randomized in a 2:2:1 fashion to either Arm A, B or C.

Arm A

        Received emicizumab prophylaxis at 3mg/kg by once-weekly
subcutaneous injection for 4 weeks, followed by 1.5 mg/kg
once-weekly subcutaneous injection

Arm B

      Received emicizumab prophylaxis at 3mg/kg by once-weekly
subcutaneous injection for 4 weeks, followed by 3 mg/kg once every
two weeks subcutaneous injection

Arm C

        No prophylaxis control arm

Patients previously treated with factor Vlll prophylactic were
enrolled in:

Arm D

        Received emicizumab prophylaxis at 3mg/kg by once-weekly
subcutaneous injection for 4 weeks, followed by 1.5 mg/kg
once-weekly subcutaneous injection

Episodic treatment of breakthrough bleeds with factor VIII therapy was
allowed per protocol.

About emicizumab clinical development status

In addition to the HAVEN 1, HAVEN 2 and HAVEN 3 studies, a global phase
lll HAVEN 4 study (NCT03020160) is currently underway by Chugai, Roche
and Genentech to evaluate emicizumab prophylaxis once every four weeks
by subcutaneous injection in hemophilia A patients with or without
factor VIII inhibitors.

About Chugai

Chugai Pharmaceutical is one of Japan’s leading research-based
pharmaceutical companies with strengths in biotechnology products.
Chugai, based in Tokyo, specializes in prescription pharmaceuticals and
is listed on the 1st section of the Tokyo Stock Exchange. As an
important member of the Roche Group, Chugai is actively involved in R&D
activities in Japan and abroad. Specifically, Chugai is working to
develop innovative products which may satisfy the unmet medical needs,
mainly focusing on the oncology area.
In Japan, Chugai’s research
facilities in Gotemba and Kamakura are collaborating to develop new
pharmaceuticals, and laboratories in Ukima are conducting research for
technology development for industrial production. Overseas, Chugai
Pharmabody Research
based in Singapore is engaged in research
focusing on the generation of novel antibody drugs by utilizing Chugai’s
proprietary innovative antibody engineering technologies. Chugai
Pharma USA
and Chugai
Pharma Europe
are engaged in clinical development activities in the
United States and Europe.
The consolidated revenue in 2016 of
Chugai totaled 491.8 billion yen and the operating income was 80.6
billion yen (IFRS Core basis).
Additional information is available
on the internet at



1)   Kitazawa, et al. Nature Medicine 2012; 18(10): 1570
2) Sampei, et al. PLoS ONE 2013; 8: e57479


For Media
Chugai Pharmaceutical Co.,
Media Relations Group, Corporate Communications Dept.,
Tel: +81-3-3273-0881
US media

Chugai Pharma USA Inc.
Paul Mignone
European media

Chugai Pharma France SAS
Nathalie Leroy
Taiwanese media

Chugai Pharma Taiwan Ltd.
Susan Chou,
Osamu Kagawa
Tel: +886-2-2715-2000

Chugai Pharmaceutical Co., Ltd.
Relations Group, Corporate Communications Dept.,
Toshiya Sasai

Source: Chugai Pharmaceutical Co., Ltd.

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