RCS - Hutchmed China Ltd - HUTCHMED Initiates Registrational Phase III Trial

HUTCHMED (China)Announcement

14/05/2024 07:00

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RNS Number : 2037O  Hutchmed (China) Limited  14 May 2024

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 (https://www.hutch-med.com/) ") (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 (https://clinicaltrials.gov/study/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
(https://clinicaltrials.gov/study/NCT04272957) ). The first-in-human
dose-escalation stage data was presented at the European Hematology
Association Congress ("EHA") in June 2023. 1  (#_edn1) 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  (#_edn2) (, 3  (#_edn3) , 4  (#_edn4) )

 

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  (#_edn5) . 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  (#_edn6)   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 (https://www.hutch-med.com/) or follow us on LinkedIn
(https://www.linkedin.com/company/hutchmed/) .

 

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                                                    +852 2121 8200 / ir@hutch-med.com (mailto:ir@hutch-med.com)

 Media Enquiries
 Ben Atwell / Alex Shaw, FTI Consulting                                +44 20 3727 1030 / +44 7771 913 902 (Mobile) /
                                                                       +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com
                                                                       (mailto:HUTCHMED@fticonsulting.com)
 Zhou Yi, Brunswick                                                    +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com
                                                                       (mailto:HUTCHMED@brunswickgroup.com)

 Nominated Advisor
 Atholl Tweedie / Freddy Crossley / Daphne Zhang, Panmure Gordon       +44 (20) 7886 2500

 

 1  (#_ednref1)   Hu L et al. P539: A Phase 1 Study of HMPL-306, a Dual
Inhibitor of Mutant Isocitrate Dehydrogenase (IDH) 1 and 2, in Patients with
Relapsed/Refractory Myeloid Hematological Malignancies Harboring IDH1 and/or 2
Mutations. Hemasphere. 2023;7(Suppl):e86312d3. Published 2023 Aug 8.
doi:10.1097/01.HS9.0000969064.86312.d3
(https://doi.org/10.1097%2F01.HS9.0000969064.86312.d3) .

 2  (#_ednref2)   S Choe S et al. Blood 2019;134(Supplement_1):545.
doi:10.1182/blood-2019-122671 (https://doi.org/10.1182/blood-2019-122671) .

 3  (#_ednref3)   Harding JJ et al. Isoform Switching as a Mechanism of
Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition. Cancer
Discov. 2018;8(12):1540-1547. doi:10.1158/2159-8290.CD-18-0877
(https://doi.org/10.1158/2159-8290.cd-18-0877) .

 4  (#_ednref4)   Delahousse J et al. Circulating oncometabolite
D-2-hydroxyglutarate enantiomer is a surrogate marker of isocitrate
dehydrogenase-mutated intrahepatic cholangiocarcinomas. Eur J Cancer.
2018;90:83-91. doi:10.1016/j.ejca.2017.11.024
(https://doi.org/10.1016/j.ejca.2017.11.024) .

 5  (#_ednref5)   Source: National Cancer Institute -
seer.cancer.gov/statfacts/html/amyl.html
(https://seer.cancer.gov/statfacts/html/amyl.html) .

 6  (#_ednref6)   Lin J et al. IDH1 and IDH2 mutation analysis in Chinese
patients with acute myeloid leukemia and myelodysplastic syndrome. Ann
Hematol. 2012;91(4):519-525. doi:10.1007/s00277-011-1352-7
(https://doi.org/10.1007/s00277-011-1352-7) .

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