Press Release
HUTCHMED Initiates the RAPHAEL Registrational Phase III Trial
of HMPL-306 for Patients with IDH1- and/or IDH2-Mutated
Relapsed/Refractory Acute Myeloid Leukemia in China
Hong Kong, Shanghai
& Florham Park, NJ - Tuesday,
May 14, 2024: HUTCHMED (China) Limited
("HUTCHMED")
(Nasdaq/AIM:HCM; HKEX:13) today announces that it has initiated a
registrational Phase III clinical trial of HMPL-306 in patients
with mutated isocitrate dehydrogenase ("IDH") 1 or 2
relapsed / refractory acute myeloid leukemia ("AML") in China.
The first patient received their first dose on May 11, 2024.
HMPL-306 is a novel dual-inhibitor of IDH1 and IDH2
enzymes. Mutations of IDH1 and IDH2 have been implicated as drivers
of certain hematological malignancies, gliomas and solid tumors,
particularly among AML patients. Although some IDH inhibitors have
been approved in certain markets for AML, isoform switching between
the cytoplasmic mutant IDH1 and mitochondrial mutant IDH2 often
leads to acquired resistance to single inhibitors of IDH1 or IDH2.
Targeting both IDH1 and IDH2 mutations may provide therapeutic
benefits in cancer patients by overcoming this acquired
resistance.
RAPHAEL is a multicenter, randomized, open-label,
registrational Phase III clinical trial designed to evaluate the
safety and efficacy of HMPL-306 as a monotherapy in patients with
relapsed or refractory AML harboring IDH1 and/or IDH2 mutations.
The primary endpoint of overall survival (OS) and the secondary
endpoints, including event-free survival (EFS) and complete
remission ("CR") rate, will be tested in comparison with current
salvage chemotherapy regimens. The Company is looking to enroll
approximately 320 patients for this registrational study, which is
being led by principal investigator Prof Xiaojun Huang of Peking
University People's Hospital. Additional details may be found at
clinicaltrials.gov, using identifier NCT06387069.
The study follows positive data from a two-stage,
open-label Phase I study evaluating the safety, pharmacokinetics,
pharmacodynamics and efficacy of HMPL-306 in this indication
(NCT04272957).
The first-in-human dose-escalation stage data was presented at the
European Hematology Association Congress ("EHA") in June
2023.[1] Results of the dose expansion
stage of the study in over 50 patients demonstrated promising CR
rates at the recommended Phase II dose are expected to be presented
at the EHA Congress in June 2024.
About IDH and Hematological Malignancies
IDHs are critical metabolic enzymes that help to break
down nutrients and generate energy for cells. When mutated, IDH
creates a molecule that alters the cell's genetic programming and
prevents cells from maturing. IDH1 or IDH2 mutations are common
genetic alterations in various types of blood and solid tumors,
including AML with approximately 14-20% of patients having mutant
IDH genes, myelodysplastic syndrome (MDS), myeloproliferative
neoplasms (MPNs), low-grade glioma and intrahepatic
cholangiocarcinoma. Mutant IDH isoform switching, either from
cytoplasmic mutant IDH1 to mitochondrial mutant IDH2, or vice
versa, is a mechanism of acquired resistance to IDH inhibition in
AML and cholangiocarcinoma.[2],[3],[4]
According to the National Cancer Institute (NCI),
there will be approximately 20,380 new cases of AML in the U.S. in
2023 and the five-year relative survival rate is 31.7%[5]. Currently, the U.S. Food and Drug Administration
(FDA) has approved two drugs for IDH1 mutation and one drug for
IDH2 mutation, but no dual inhibitor targeting both IDH1 and IDH2
mutants has been approved. There were an estimated 19,700 new cases
of AML in China in 2018 and is estimated to reach 24,200 in China
in 2030.[6] In China one IDH1
inhibitor was approved in 2022.
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 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 HMPL-306 for the treatment of patients
with relapsed or refractory AML and the further development of
HMPL-306 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 HMPL-306 for the treatment of patients
with relapsed or refractory AML 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 HMPL-306, HUTCHMED's ability to
fund, implement and complete its further clinical development and
commercialization plans for HMPL-306 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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