Press Release
HUTCHMED Initiates Registration Stage of the
ESLIM-02 Phase II/III Trial of Sovleplenib for Warm Antibody
Autoimmune Hemolytic Anemia in China
Hong Kong, Shanghai
& Florham Park, NJ - Friday, March 22,
2024: HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM;
HKEX:13) today announces that it has initiated the registration
stage of the Phase II/III clinical trial of sovleplenib in adult
patients with warm antibody autoimmune hemolytic anemia ("wAIHA")
in China.
This follows positive data from the proof-of-concept
Phase II stage of the trial and subsequent consultation with the
China National Medical Products Administration ("NMPA"). If
positive, the data from the trial may be used to support a future
New Drug Application ("NDA") filing. wAIHA is an autoimmune
disorder that can lead to anemia and has limited treatment options.
The first Phase III patient received their initial dose on March
20, 2024.
ESLIM-02 is a randomized, double blind,
placebo-controlled Phase II/III clinical trial. The objective of
the registration stage of the study is to confirm the safety and
efficacy of sovleplenib in adult patients with wAIHA. The primary
endpoint for the study is the proportion of patients who achieve a
durable hemoglobin (Hb) response by Week 24. 21 patients have been
enrolled in the study so far and approximately 90 more patients are
expected to be enrolled to this registration stage. The lead
principal investigators are Dr. Fengkui Zhang of Chinese Academy of
Medical Sciences Blood Diseases Hospital, Dr. Bing Han of Chinese
Academy of Medical Sciences Peking Union Medical College Hospital
and Dr. Liansheng Zhang of Lanzhou University Second Hospital.
Additional details may be found at clinicaltrials.gov, using
identifier NCT05535933.
About Sovleplenib
Sovleplenib is a novel, investigational, selective
small molecule inhibitor for oral administration targeting the
spleen tyrosine kinase, also known as Syk. Syk is a major component
in B-cell receptor and Fc receptor signaling and is an established
target for the treatment of multiple subtypes of B-cell lymphomas
and autoimmune disorders. HUTCHMED currently retains all rights to
sovleplenib worldwide.
In addition to wAIHA, sovleplenib is also being
studied in immune thrombocytopenia ("ITP"). ESLIM-01 (NCT05029635)
is a randomized, double-blinded, placebo-controlled Phase III trial
in China of sovleplenib in patients with primary ITP
that met all its endpoints. ITP is an autoimmune disorder that
can lead to increased risk of bleeding. The NMPA granted
Breakthrough Therapy designation for this indication and
accepted the New Drug Application (NDA) for review with Priority
Review in January 2024. A dose-finding study in the U.S. is in
planning (NCT06291415).
About wAIHA and Syk
AIHA is an autoimmune disorder characterized by the
destruction of red blood cells ("RBCs") due to the production of
antibodies against RBC. The incidence of AIHA is estimated to be
0.8-3.0/100,000 adults per year with an estimated prevalence of 17
per 100,000 adults and a death rate of 8%-11%.[1],[2] wAIHA is the
most common form of the autoimmune hemolytic diseases,[3] accounting for about 75-80% of all adult AIHA
cases.[4]
The accelerated clearance of antibody-coated RBCs by
immunoglobulin Fc receptor ("FcR") bearing macrophages is thought
to be the pathogenic mechanism in wAIHA.[5]
Activation of the FcR is associated with a signaling subunit, FcRγ,
whose phosphorylation subsequent to receptor binding results in the
recruitment and activation of Syk.[6]
Activated Syk mediates downstream signaling of the activated FcRs
in phagocytic cells, resulting in phagocytosis of RBCs.[7] In addition, activation of Syk through the B-cell
receptor mediates activation and differentiation of B-lymphocytes
into antibody secreting plasma cells.[8]
Therefore, inhibition of Syk may have potential effects in the
treatment of wAIHA through inhibition of phagocytosis and reduction
of antibody production.
About HUTCHMED
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative,
commercial-stage, biopharmaceutical company. It is committed to the
discovery, global development and commercialization of targeted
therapies and immunotherapies for the treatment of cancer and
immunological diseases. It has approximately 5,000 personnel across
all its companies, at the center of which is a team of about 1,800
in oncology/immunology. Since inception, HUTCHMED has focused on
bringing cancer drug candidates from in-house discovery to patients
around the world, with its first three oncology medicines now
marketed in China, the first of which is also marketed in the U.S.
For more information, please visit: www.hutch‑med.com or follow us on
LinkedIn.
Forward-Looking
Statements
This press release contains forward-looking
statements within the meaning of the "safe harbor" provisions of
the U.S. Private Securities Litigation Reform Act of 1995. These
forward-looking statements reflect HUTCHMED's current expectations
regarding future events, including its expectations regarding the
therapeutic potential of sovleplenib for the treatment of patients
with wAIHA and the further development of sovleplenib in this and
other indications. Forward-looking statements involve risks and
uncertainties. Such risks and uncertainties include, among other
things, assumptions regarding the timing and outcome of clinical
studies and the sufficiency of clinical data to support an NDA
submission of sovleplenib for the treatment of patients with wAIHA
or other indications in China or other jurisdictions, its potential
to gain approvals from regulatory authorities on an expedited basis
or at all, the efficacy and safety profile of sovleplenib,
HUTCHMED's ability to fund, implement and complete its further
clinical development and commercialization plans for sovleplenib
and the timing of these events. Existing and prospective investors
are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date hereof. For further
discussion of these and other risks, see HUTCHMED's filings with
the U.S. Securities and Exchange Commission, The Stock Exchange of
Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to
update or revise the information contained in this press release,
whether as a result of new information, future events or
circumstances or otherwise.
Medical Information
This press release contains information about
products that may not be available in all countries, or may be
available under different trademarks, for different indications, in
different dosages, or in different strengths. Nothing contained
herein should be considered a solicitation, promotion or
advertisement for any prescription drugs including the ones under
development.
CONTACTS
Investor Enquiries
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+852 2121 8200 /
ir@hutch-med.com
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Media Enquiries
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Ben Atwell / Alex Shaw,
FTI Consulting
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+44 20 3727 1030 /
+44 7771 913 902 (Mobile) /
+44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com
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Zhou Yi, Brunswick
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+852 9783 6894 (Mobile) /
HUTCHMED@brunswickgroup.com
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Nominated Advisor
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Atholl Tweedie /
Freddy Crossley / Daphne Zhang,
Panmure Gordon
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+44 (20) 7886 2500
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[1] Eaton WW, Rose NR,
Kalaydjian A, Pedersen MG, Mortensen PB. Epidemiology of autoimmune
diseases in Denmark. J Autoimmun. 2007; 29 (1):1-9. doi:
10.1016/j.jaut.2007.05.002.
[2]
Roumier M, Loustau V, Guillaud C, et al.
Characteristics and outcome of warm autoimmune hemolytic anemia in
adults: new insights based on a single-center experience with 60
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10.1002/ajh.23767.
[3] Cotran Ramzi S,
Kumar Vinay, Fausto Nelson, Nelso Fausto, Robbins Stanley L, Abbas
Abul K. Robbins and Cotran pathologic basis of disease. St. Louis,
Mo: Elsevier Saunders; 2005. p. 637.
[4] Gehrs BC, Friedberg
RC. Autoimmune haemolytic anemia. Am J Hematol.
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[5] Barros MM,
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recent progress in understanding the immunobiology and the
treatment. Transfus Med Rev. 2010; 24(3):195‐210. doi: 10.1016/j.tmrv.2010.03.002.
[6] Braselmann S,
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[7] Barcellini W,
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autoimmune hemolytic anemia. Expert Rev Clin Immunol. 2018;
14(10):857‐872. doi:
10.1080/1744666x.2018.1521722.
[8] Davidzohn N, Biram
A, Stoler‐Barak L, Grenov A, Dassa B,
Shulman Z. SYK degradation restrains plasma cell formation and
promotes zonal transitions in germinal centers. J Exp Med. 2020;
217(3):e20191043. doi: 10.1084/jem.20191043.