RCS - Hutchmed China Ltd - Breakthrough Therapy Designation in China

HUTCHMED (China)Announcement

12/12/2024 07:00

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RNS Number : 8395P  Hutchmed (China) Limited  12 December 2024

Press Release

 

HUTCHMED Announces Breakthrough Therapy Designation in China for ORPATHYS(®) and TAGRISSO(®) Combination in Certain Lung Cancer Patients After Disease Progression on EGFR Inhibitor Therapy

 

Hong Kong, Shanghai & Florham Park, NJ - Thursday, December 12, 2024:
HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM:HCM; HKEX:13) today announces that the Center for Drug Evaluation
of China's National Medical Products Administration ("NMPA") has granted
Breakthrough Therapy Designation ("BTD") to 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 EGFR inhibitor therapy.
ORPATHYS(®) is an oral, potent and highly selective MET tyrosine kinase
inhibitor ("TKI"). TAGRISSO(®) is a third-generation, irreversible EGFR TKI.

 

This treatment combination is being evaluated in China in the ongoing
multi-center, open-label, randomized, controlled, Phase III SACHI trial. The
study is investigating 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 patients with locally advanced or metastatic NSCLC with MET
amplification after failure of EGFR inhibitor therapy. The primary endpoint of
the study is 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
(NCT05015608 (https://clinicaltrials.gov/ct2/show/NCT05015608) ).

 

NMPA grants BTD to new drugs that treat life-threatening diseases or serious
conditions for which there are no effective treatment options, and where
clinical evidence demonstrates significant advantages over existing therapies.
Drug candidates with BTD may be considered for conditional approval and
priority review when submitting an NDA. This indicates that the development
and review of the therapy for this disease indication may be expedited, to
address patients' unmet needs more quickly.

 

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) and SAVANNAH (NCT03778229) studies. The encouraging results from
these studies led to the initiation of three Phase III trials with this
combination: SACHI (NCT05015608) and SANOVO (NCT05009836) were initiated in
China in 2021, and the global, pivotal Phase III SAFFRON (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. 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 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 US 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 US 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 / Rupert Dearden, Panmure Liberum      +44 (20) 7886 2500

 

 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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