Chugai Presents Results from Phase III Study of Satralizumab in NMOSD at ECTRIMS 2018

– Satralizumab added to baseline therapy significantly reduced risk of
relapse –

TOKYO–(BUSINESS WIRE)–#NMOSDChugai
Pharmaceutical Co., Ltd.
(TOKYO:4519) announced that results from
the phase III study of satralizumab (development code: SA237), SAkuraSky
Study (NCT02028884), were presented at the Congress of European
Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
2018 held in Berlin, Germany from October 10 to 12. Satralizumab is a
humanized investigational recycling anti-IL-6 receptor monoclonal
antibody for the treatment of neuromyelitis optica spectrum disorder
(NMOSD), which currently has no approved treatments.

“These positive pivotal results for satralizumab, showing a significant
reduction in relapses in patients, are a significant positive step in
the potential treatment of NMOSD,” said Dr. Takashi Yamamura, Director,
Department of Immunology, National Institute of Neuroscience, National
Center of Neurology and Psychiatry, Tokyo. “Many people with NMOSD are
suffering from frequent relapses and often persistent motor dysfunction
and loss of sensation, and end up relying on wheelchairs or going blind.
The medical community hopes that this potential new medicine may
alleviate the condition and improve the everyday lives of people who
currently have no approved treatment options.”

The phase III study results for SAkuraSky study showed:

  • Satralizumab on top of immunosuppressive therapy significantly reduced
    the risk of relapse by 62% (hazard ratio = 0.38 [95% confidence
    interval: 0.16-0.88], p=0.0184 [stratified log-rank test]) in patients
    with NMOSD including anti-aquaporin-4 (AQP4) antibody positive (AQP4
    Ab positive) and negative (AQP4 Ab negative) patients, achieving the
    primary endpoint of time to first protocol-defined relapse (PDR) in
    the double-blind period. The proportion of relapse free at weeks 48
    and 96 was 88.9% and 77.6% with satralizumab and 66.0% and 58.7% with
    placebo, respectively.
  • In a prespecified subgroup analysis, satralizumab showed a 79% risk
    reduction (N=55, hazard ratio=0.21 [95% confidence interval:
    0.06-0.75]) of PDR compared to placebo in the NMOSD AQP4 Ab positive
    subgroup. The proportion of relapse free at weeks 48 and 96 was 91.5%
    and 91.5% with satralizumab and 59.9% and 53.3% with placebo,
    respectively. For the NMOSD AQP4 Ab negative subgroup, satralizumab
    showed a 34% risk reduction (N= 28, hazard ratio= 0.66 [95% confidence
    interval: 0.20-2.23]) of PDR compared to placebo, and the proportion
    of relapse free at weeks 48 and 96 was 84.4% and 56.3% with
    satralizumab, and 75.5% and 67.1% with placebo, respectively.
  • Throughout the mean treatment duration of approximately 2 years,
    satralizumab showed a favorable safety profile. The proportion of
    patients experiencing serious adverse events, including serious
    infections, was similar in patients treated with satralizumab or
    placebo. No death or anaphylactic reactions were observed.

“The positive phase III results for satralizumab suggests that IL-6
inhibition should be an effective therapeutic approach for NMOSD,” said
Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project &
Lifecycle Management Unit. “NMOSD is a disease with significant unmet
medical needs. Although progression of the disease may lead to blindness
and motor dysfunction, there are no approved drugs available. We
continue our efforts so that we can hopefully bring this treatment
option to people living with this devastating disease.”

SAkuraSky Study

Summary:

A phase III multicenter, randomized, double-blind,
placebo-controlled study to evaluate the efficacy and safety of
satralizumab added to baseline therapy in patients with NMOSD

 
   

Primary Endpoint

Time to first protocol-defined relapse adjudicated by an independent
review committee in the double-blind period

 

Main Secondary Endpoints

Change in Visual Analogue Scale (VAS) score for pain
Change in Functional Assessment of Chronic Illness Therapy (FACIT)
Fatigue score

Study Design:

  • 83 male and female patients aged from 13 to 73 years were randomized.
  • Patients were randomized to either of the following two treatment
    groups in a 1:1 ratio. Satralizumab (120 mg) or placebo added to
    baseline therapy (azathioprine, mycophenolate mofetil and/or
    corticosteroids). Both treatments were subcutaneously administered at
    Week 0, 2, and 4. The subsequent treatment was continued at 4-week
    intervals.
  • The double-blind period ended when the total number of
    protocol-defined relapse reached 26. After completion of the
    double-blind period, patients in both groups were able to continue
    treatment with satralizumab in an open-label extension period.
  • Patients with neuromyelitis optica (as defined by diagnostic criteria
    in 2006) and those with NMOSD (as defined by diagnostic criteria in
    2007) with anti- AQP4 antibodies, were enrolled.

About Neuromyelitis Optica Spectrum Disorder (NMOSD)
Neuromyelitis
optica spectrum disorder (NMOSD) is a rare, lifelong, and debilitating
autoimmune disease of the central nervous system (CNS) characterized by
inflammatory lesions in the optic nerves and spinal cord. Patients with
NMOSD frequently experience a relapsing disease course with repeated
attacks leading to accumulating neurological damage and disability.
Symptoms may include visual impairment, motor disability, and loss of
quality of life. In some cases, attacks of NMOSD result in death.

NMOSD pathogenesis is thought to involve AQP4-IgG autoantibody entry
into the CNS, however approximately one-third of patients with NMOSD are
AQP4-IgG seronegative. The inflammatory cytokine IL-6 is now emerging as
an important factor in NMOSD pathogenesis.

Diagnostic criteria introduced in 2006 for neuromyelitis optica were
characterized by inflammation of the optic nerve (optic neuritis) and
the spinal cord (myelitis). These were revised in 2007 with the
definition of NMOSD, proposed for diseases with either optic neuritis or
myelitis. In 2015, the definition of NMOSD further revised to include a
broader spectrum of disease. The diagnostic term NMOSD is now widely
used.

References

  • Jarius S, Ruprecht K, Wildemann B et al. Contrasting disease patterns
    in seropositive and seronegative neuromyelitis optica: A multicentre
    study of 175 patients. J Neuroinflammation 2012;9:14.
  • Lennon VA, Wingerchuk DM, Kryzer TJ et al. A serum autoantibody marker
    of neuromyelitis optica: distinction from multiple sclerosis. Lancet
    2004;364:2106-12.
  • Marignier R, Bernard-Valnet R, Giraudon P et al. Aquaporin-4
    antibody-negative neuromyelitis optica: Distinct assay
    sensitivity-dependent entity. Neurology 2013;80:2194-200.
  • Takahashi T, Fujihara K, Nakashima I et al. Anti-aquaporin-4 antibody
    is involved in the pathogenesis of NMO: a study on antibody titre.
    Brain 2007;130:1235-43.
  • Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised diagnostic
    criteria for neuromyelitis optica. Neurology 2006;66:1485-9.
  • Wingerchuk DM, Lennon VA, Lucchinetti CF, et al. The spectrum of
    neuromyelitis optica. Lancet Neurol 2007;6:805 15.
  • Wingerchuk DM, Banwell B, Bennett JL et al. International consensus
    diagnostic criteria for neuromyelitis optica spectrum disorders.
    Neurology 2015;85:177-89.

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 2017 of
Chugai totalled 534.2 billion yen and the operating income was 103.2
billion yen (IFRS Core basis).
Additional information is available
on the internet at https://www.chugai-pharm.co.jp/english.

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