Press Release
HUTCHMED Announces Savolitinib sNDA Accepted in China for
Treatment-Naïve or Previously Treated Patients
with Locally Advanced or Metastatic MET Exon 14 NSCLC
- Oral presentation at the European Lung Cancer
Congress 2024 of Phase IIIb data demonstrating median PFS of 13.7
months and median OS not reached in treatment-naïve
patients -
- If approved, would confirm 2021 conditional
approval and expand indication to more patients -
Hong Kong, Shanghai
& Florham Park, NJ - Thursday, March 28, 2024: HUTCHMED
(China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM;
HKEX:13) today announces that the supplemental New Drug Application
("sNDA") for savolitinib, in adult patients with locally advanced
or metastatic non-small cell lung cancer ("NSCLC") with mesenchymal
epithelial transition factor ("MET") exon 14 skipping alteration,
has been accepted for review by the China National Medical Products
Administration (NMPA). If approved, the new label indication for
savolitinib will be expanded to include treatment-naive patients in
China.
Savolitinib was previously granted conditional
approval in China for the treatment of patients with NSCLC with MET
exon 14 skipping alterations who have progressed following prior
systemic therapy or are unable to receive chemotherapy.
Savolitinib was launched and is marketed under the brand name
ORPATHYS® by our partner, AstraZeneca for this patient
population, representing the first selective MET inhibitor approved
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.
Preliminary efficacy and safety data from the
first-line cohort of the confirmatory Phase IIIb clinical trial
(NCT04923945)
were presented during the IASLC World Conference on Lung Cancer
(WCLC) in September 2023. Final data from the confirmatory Phase
IIIb trial were presented at the European Lung Cancer Congress on
March 20, 2024.
The data from this study provide confirmatory evidence
for savolitinib as a targeted treatment option for treatment-naïve
or previously treated patients with MET exon 14 skipping alteration
NSCLC. In treatment-naïve patients, objective response rate ("ORR")
was 62.1% (95% CI: 51.0% to 72.3%), disease control rate ("DCR")
was 92.0% (95% CI: 84.1% to 96.7%) and median duration of response
("DoR") was 12.5 months (95% CI: 8.3 months to 15.2 months), as
assessed by an independent review committee. Median progression
free survival ("PFS") was 13.7 months (95% CI: 8.5 months to 16.6
months) and median overall survival ("OS") was not reached with
median follow-up of 20.8 months. In previously treated patients,
ORR was 39.2% (95% CI: 28.4% to 50.9%), DCR was 92.4% (95% CI:
84.2% to 97.2%) and median DoR was 11.1 months (95% CI: 6.6 months
to not reached), as assessed by an independent review committee.
Median PFS was 11.0 months (95% CI: 8.3 months to 16.6 months) and
median OS was not mature with median follow-up of 12.5 months.
Responses occurred early (time to response 1.4-1.6 months) in both
treatment-naïve and previously treated patients. The safety profile
was tolerable and no new safety signals were observed. The most
common drug-related treatment-emergent adverse events of Grade 3 or
above (5% or more of patients) were abnormal hepatic function
(16.9%), increased alanine aminotransferase (14.5%), increased
aspartate aminotransferase (12.0%), peripheral oedema (6.0%) and
increased gamma-glutamyltransferase (6.0%).
About NSCLC and MET aberrations
Lung cancer is the leading cause of cancer death among
men and women, 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 U.S. and Europe and
30-40% of patients in Asia have 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 TKIs 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] 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 depends on the sample type, detection method and
assay cut-off used.[15]
About Savolitinib (ORPATHYS® in
China)
Savolitinib is an oral, potent and highly selective
MET tyrosine kinase inhibitor 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.
Savolitinib is
marketed in China under the brand name ORPATHYS® for
the treatment of patients with non-small cell lung cancer with MET
exon 14 skipping alterations who have progressed following prior
systemic therapy or are unable to receive chemotherapy. It 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. Starting on March 1, 2023,
ORPATHYS® was included
in the National Reimbursement Drug List (NRDL) for the treatment of
locally advanced or metastatic NSCLC adult patients with MET exon
14-skipping alterations who have progressed after or unable to
tolerate platinum-based chemotherapy.
In 2011, AstraZeneca and HUTCHMED entered a global
licensing and collaboration agreement to jointly develop and
commercialize savolitinib. Joint development of savolitinib in
China is led by HUTCHMED, while AstraZeneca leads development
outside of China. HUTCHMED is responsible for the marketing
authorization, manufacturing and supply of savolitinib in China.
AstraZeneca is responsible for the commercialization of savolitinib
in China and worldwide. Sales of savolitinib are recognized by
AstraZeneca.
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 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, 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. 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
|
+44 20 3727 1030 /
+44 7771 913 902 (Mobile) /
+44 7779 545 055 (Mobile) /
HUTCHMED@fticonsulting.com
|
Zhou Yi, Brunswick
|
+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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[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).