RCS - Hutchmed China Ltd - China NDA Acceptance for ORPATHYS and TAGRISSO

HUTCHMED (China)Announcement

02/01/2025 07:15

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RNS Number : 8076R  Hutchmed (China) Limited  02 January 2025

Press Release

 

HUTCHMED Announces NDA Acceptance in China with Priority Review Status for ORPATHYS(®) and TAGRISSO(®) Combination in Lung Cancer Patients with MET amplification After Progression on First-Line EGFR Inhibitor Therapy

 

Hong Kong, Shanghai & Florham Park, NJ - Thursday, January 2, 2025:
HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM:HCM; HKEX:13) today announces that the New Drug Application
("NDA") for the combination of ORPATHYS(®) (savolitinib) and
TAGRISSO(®) (osimertinib) for the treatment of patients with locally
advanced or metastatic epidermal growth factor receptor ("EGFR")
mutation-positive non-small cell lung cancer ("NSCLC") with MET amplification
after disease progression on first-line EGFR inhibitor therapy has been
accepted and granted priority review by the China National Medical Products
Administration ("NMPA"). ORPATHYS(®) is an oral, potent and highly selective
MET tyrosine kinase inhibitor ("TKI"). TAGRISSO(®) is a third-generation,
irreversible EGFR TKI. This acceptance also triggers a milestone payment from
AstraZeneca.

 

The NDA is supported by data from SACHI, a multi-center, open-label,
randomized, controlled, Phase III trial which evaluated the efficacy and
safety of a combination of ORPATHYS(®) and TAGRISSO(®) compared to
platinum-based doublet-chemotherapy (pemetrexed plus cisplatin or
carboplatin), the standard-of-care treatment option in this setting. The
primary endpoint of the study was progression free survival ("PFS") as
assessed by investigators. Other endpoints include PFS assessed by an
independent review committee, overall survival (OS), objective response rate
(ORR), duration of response (DoR), disease control rate (DCR), time to
response (TTR), and safety. The Independent Data Monitoring Committee ("IDMC")
of SACHI has considered that the study has met the pre-defined primary
endpoint of PFS in a planned interim analysis and as a result, enrollment into
the study has concluded. Results from SACHI will be submitted for presentation
at an upcoming scientific conference (clinicaltrials.gov identifier
NCT05015608 (https://clinicaltrials.gov/ct2/show/NCT05015608) ).

 

"This marks the first regulatory filing for the ORPATHYS(®) and TAGRISSO(®)
combination. The combination has demonstrated clear evidence to address
MET-driven EGFR-inhibitor resistance and offers a continued path for oral
treatment." said Dr Michael Shi, Head of R&D and Chief Medical Officer of
HUTCHMED. "With our biomarker-specific approach, we are hopeful to enhance
treatment continuity and quality of life for NSCLC patients navigating this
challenging journey. We and our partner AstraZeneca have been exploring this
combination globally, through an array of late-stage clinical trials including
the TATTON, SAVANNAH, SAFFRON and ORCHARD studies, and we hope to bring this
all-oral, chemotherapy-free treatment option to patients with MET-driven lung
cancer in the near future."

 

The NMPA granted Breakthrough Therapy designation to the combination of
ORPATHYS(®) and TAGRISSO(®) for this potential indication in December 2024.
The NMPA granted this designation to this combination as a new treatment that
could target a serious condition where clinical evidence demonstrates
substantial advantages over existing therapies.

 

About NSCLC and MET aberrations

Lung cancer is the leading cause of cancer death, accounting for about
one-fifth of all cancer deaths. 1  Lung cancer is broadly split into NSCLC and
small cell lung cancer, with 80-85% classified as NSCLC. 2  The majority of
NSCLC patients (approximately 75%) are diagnosed with advanced disease, and
approximately 10-15% of NSCLC patients in the US and Europe and 30-40% of
patients in Asia have EGFR-mutated ("EGFRm") NSCLC.  3 (, 4 , 5 , 6 )

 

MET is a tyrosine kinase receptor that has an essential role in normal cell
development. 7  MET overexpression and/or amplification can lead to tumor
growth and the metastatic progression of cancer cells, and is one of the
mechanisms of acquired resistance to EGFR TKI for metastatic EGFR-mutated
NSCLC. (7, 8 ) Approximately 2-3% of NSCLC patients have tumors with MET exon
14 skipping alterations, a targetable mutation in the MET gene. 9  MET
aberration is a major mechanism for acquired resistance to both
first/second-generation EGFR TKIs as well as third-generation EGFR TKIs like
osimertinib. Among patients who experience disease progression
post-osimertinib treatment, approximately 15-50% present with MET
aberration. 10 (, 11 , 12 , 13 , 14 ) The prevalence of MET aberration depends
on the sample type, detection method and assay thresholds used. 15 

 

About ORPATHYS(®) and TAGRISSO(®) Combination Development in EGFR mutation-positive NSCLC

The combination of ORPATHYS(®) and TAGRISSO(®) has been studied extensively
in patients with EGFR mutation-positive NSCLC, including the TATTON
(NCT02143466 (https://clinicaltrials.gov/study/NCT02143466) ) and SAVANNAH
(NCT03778229 (https://clinicaltrials.gov/study/NCT03778229) ) studies. The
encouraging results from these studies led to the initiation of three Phase
III trials with this combination: SACHI (NCT05015608
(https://clinicaltrials.gov/study/NCT05015608) ) and SANOVO (NCT05009836
(https://clinicaltrials.gov/study/NCT05009836) ) were initiated in China in
2021, and the global, pivotal Phase III SAFFRON (NCT05261399
(https://clinicaltrials.gov/study/NCT05261399) ) study started enrollment in
2022. In comparison to other treatment options, this combination treatment is
chemotherapy-free, biomarker-specific and orally administered, aiming for a
balanced efficacy, safety and quality-of-life profile for lung cancer
patients.

 

SAVANNAH is a global Phase II study in patients who have progressed following
osimertinib due to MET amplification or overexpression, and recruitment
completed earlier in 2024. The evaluation of savolitinib in combination with
osimertinib was designated as a Fast Track development program by the US Food
and Drug Administration (FDA) in 2023.

 

SAFFRON is a multi-center, randomized, controlled, open-label, global Phase
III trial in patients with EGFR mutation-positive NSCLC with MET
overexpression and/or amplification after disease progression on osimertinib.

 

SACHI is a multi-center, randomized, controlled, open-label, China Phase III
trial in patients with EGFR mutation-positive NSCLC with MET amplification
after disease progression on any EGFR inhibitor therapy, including
third-generation EGFR-TKIs such as osimertinib.

 

SANOVO is a multi-center, randomized, controlled, blinded, China Phase III
trial in treatment-naïve patients with EGFR mutation-positive NSCLC with
MET-positive tumors.

 

About ORPATHYS(®) Approval in China

ORPATHYS(®) was granted conditional approval in China for the treatment of
patients with locally advanced or metastatic NSCLC with MET exon 14 skipping
alterations who have progressed following prior systemic therapy or are unable
to receive chemotherapy. ORPATHYS(®) is the first selective MET inhibitor
approved in China. It has been included
(https://www.hutch-med.com/orpathys-nrdl-inclusion/) in the National
Reimbursement Drug List of China (NRDL) since March 2023. A supplementary NDA
is under review which, if approved, could expand this indication to include
treatment‑naïve adult patients in China. More than a third of the world's
lung cancer patients are in China and, among those with NSCLC globally,
approximately 2-3% have tumors with MET exon 14 skipping alterations.

 

About ORPATHYS(®) (savolitinib)

ORPATHYS(®) is an oral, potent and highly selective MET TKI that has
demonstrated clinical activity in advanced solid tumors. It blocks atypical
activation of the MET receptor tyrosine kinase pathway that occurs because of
mutations (such as exon 14 skipping alterations or other point mutations),
gene amplification or protein overexpression.

 

ORPATHYS(®) is marketed in China and is currently under clinical development
for multiple tumor types, including lung, kidney and gastric cancers, as a
single treatment and in combination with other medicines.

 

In 2011, AstraZeneca and HUTCHMED entered a global licensing and collaboration
agreement to jointly develop and commercialize ORPATHYS(®). Joint development
of ORPATHYS(®) in China is led by HUTCHMED, while AstraZeneca leads
development outside of China. HUTCHMED is responsible for the marketing
authorization, manufacturing and supply of ORPATHYS(®) in China. AstraZeneca
is responsible for the commercialization of ORPATHYS(®) in China and
worldwide. Sales of ORPATHYS(®) are recognized by AstraZeneca.

 

About TAGRISSO(®)

TAGRISSO(®) (osimertinib) is a third-generation, irreversible EGFR-TKI with
proven clinical activity in NSCLC, including against central nervous system
(CNS) metastases. TAGRISSO(®) (40mg and 80mg once-daily oral tablets) has
been used to treat nearly 800,000 patients across its indications worldwide
and AstraZeneca continues to explore TAGRISSO(®) as a treatment for patients
across multiple stages of EGFRm NSCLC.

 

There is an extensive body of evidence supporting the use of TAGRISSO(®) as
standard of care in EGFRm NSCLC. TAGRISSO(®) improved patient outcomes in
early-stage disease in the ADAURA Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-demonstrated-strong-overall-survival-benefit-in-the-adaura-phase-iii-trial.html)
, locally advanced disease in the LAURA Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-improved-pfs-in-stage-iii-lung-cancer.html)
, late-stage disease in the FLAURA Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2019/tagrisso-significantly-improves-overall-survival-in-the-phase-iii-flaura-trial-for-1st-line-egfr-mutated-non-small-cell-lung-cancer-09082019.html)
, and with chemotherapy in the FLAURA2 Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-plus-chemotherapy-extended-median-progression-free-survival-by-nearly-9-months-in-egfr-mutated-advanced-lung-cancer-in-flaura2-phase-iii-trial.html)
.

 

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. Since inception,
HUTCHMED has focused on bringing drug candidates from in-house discovery to
patients around the world, with its first three medicines marketed in China,
the first of which is also approved in the US, Europe and Japan. 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, includ-ing its expectations regarding
the thera-peutic potential of savolitinib, the further clinical develop-ment
for savolitinib, its expectations as to whether any studies on savolitinib
would meet their primary or secondary endpoints, and its expectations as to
the timing of the completion and the release of results from such studies.
Forward-looking statements involve risks and uncertainties. Such risks and
uncertainties include, among other things, assumptions regarding enrollment
rates and the timing and availability of subjects meeting a study's inclusion
and exclusion criteria; changes to clinical protocols or regulatory
requirements; unexpected adverse events or safety issues; the ability of
savolitinib, including as a combination therapy, to meet the primary or
secondary endpoint of a study, to obtain regulatory approval in different
jurisdictions and to gain commercial acceptance after obtaining regulatory
approval; the potential market of savolitinib for a targeted indication; and
the sufficiency of funding. In addition, as certain studies rely on the use of
other drug products such as osimertinib as combination therapeutics with
savolitinib, such risks and uncertainties include assumptions regarding the
safety, efficacy, supply and continued regulatory approval of these
therapeutics. 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
 FTI Consulting -                                     +44 20 3727 1030 / HUTCHMED@fticonsulting.com
                                                      (mailto:HUTCHMED@fticonsulting.com)
 Ben Atwell / Alex Shaw                               +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)
 Brunswick - Zhou Yi                                  +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com
                                                      (mailto:HUTCHMED@brunswickgroup.com)

 Panmure Liberum                                      Nominated Advisor and Joint Broker
 Atholl Tweedie / Freddy Crossley / Rupert Dearden    +44 20 7886 2500

 HSBC                                                 Joint Broker
 Simon Alexander / Alina Vaskina / Arnav Kapoor       +44 20 7991 8888

 Cavendish                                            Joint Broker
 Geoff Nash / Nigel Birks                             +44 20 7220 0500

 

 1   World Health Organization. International Agency for Research on Cancer.
All cancers fact sheet. Available at:
https://gco.iarc.fr/today/-data/factsheets/cancers/39-All-cancers-fact-sheet.pdf
(https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf)
. Accessed November 2022.

 2   American Cancer Society. What is Lung Cancer? Available at:
https://www.cancer.org/cancer/lung-cancer/about/what-is.html
(https://www.cancer.org/cancer/lung-cancer/about/what-is.html) . Accessed
November 2022.

 3  Knight SB, et al. Progress and prospects of early detection in lung
cancer. Open Biol. 2017;7(9): 170070.

 4  Keedy VL, et al. American Society of Clinical Oncology Provisional
Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for
Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR
Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27.

 5  Zhang Y, et al. The prevalence of EGFR mutation in patients with non-small
cell lung cancer: a systematic review and meta-analysis. Oncotarget.
2016;7(48).

 6  Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and
Histological Samples in 11. Non-Small Cell Lung Cancer: a Polish, Single
Institution Study and Systematic Review of European Incidence. Int J Clin
Exp Pathol. 2013:6;2800-12.

 7  Uchikawa E, et al. Structural basis of the activation of c-MET receptor.
Nat Commun. 2021;12(4074).

 8  Wang Q, et al. MET inhibitors for targeted therapy of EGFR TKI-resistant
lung cancer. Journal of Hematology & Oncology. 2019;63.

 9  Vuong HG, et al. Clinicopathological implications of MET exon 14 mutations
in non-small cell lung cancer - A systematic review and meta-analysis. Lung
Cancer. 2018; 123: 76-82.

 10  Soria JC, et al. Osimertinib in Untreated EGFR-Mutated Advanced
Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125.

 11  Mok TS, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive
Lung Cancer. N Engl J Med. 2017;376(7):629-640.

 12  Hartmaier R, et al. Tumor genomics in patients (pts) with advanced
epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer
(NSCLC) whose disease has progressed on first-line (1L) osimertinib therapy in
the Phase II ORCHARD study. Cancer Res 15 June 2022; 82
(12_Supplement): LB078.

 13  Piotrowska, et al.  MET amplification (amp) as a resistance mechanism to
osimertinib. Journal of Clinical Oncology 2017 35:15_suppl, 9020-9020.

 14  Hartmaier, et al. Detection of MET-mediated EGFR tyrosine kinase
inhibitor (TKI) resistance in advanced non-small cell lung cancer (NSCLC):
biomarker analysis of the TATTON study. Cancer Res (2019) 79 (13_Supplement):
4897.

 15  Coleman N, et al. Beyond epidermal growth factor receptor: MET
amplification as a general resistance driver to targeted therapy in
oncogene-driven non-small-cell lung cancer. ESMO Open. 2019;6(6).

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