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
HUTCHMED announces that its New Drug Application (NDA) for the combination of ORPATHYS® and TAGRISSO® has been accepted with priority review status by China's NMPA. The treatment targets patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer with MET amplification after disease progression on first-line EGFR inhibitor therapy.
The NDA is supported by data from the Phase III SACHI trial, which evaluated the combination therapy against standard platinum-based doublet-chemotherapy. The study met its primary endpoint of progression-free survival in a planned interim analysis. The acceptance triggers a milestone payment from AstraZeneca.
The NMPA granted Breakthrough Therapy designation to this combination in December 2024, recognizing it as a potential new treatment showing substantial advantages over existing therapies.
HUTCHMED annuncia che la sua Domanda per un Nuovo Farmaco (NDA) per la combinazione di ORPATHYS® e TAGRISSO® è stata accettata con status di revisione prioritaria dalla NMPA della Cina. Il trattamento è destinato a pazienti con cancro ai polmoni non a piccole cellule, con mutazione EGFR positiva e amplificazione MET in fase localmente avanzata o metastatica, dopo progressione della malattia con terapia di inibitori EGFR di prima linea.
La NDA è supportata dai dati della fase III dello studio SACHI, che ha valutato la terapia combinata rispetto alla chemioterapia standard a base di platino. Lo studio ha raggiunto il suo obiettivo primario di sopravvivenza libera da progressione in un'analisi intermedia pianificata. L'accettazione attiva un pagamento di milestone da AstraZeneca.
Nel dicembre 2024, la NMPA ha concesso la designazione di Terapia Innovativa a questa combinazione, riconoscendola come un potenziale nuovo trattamento che mostra vantaggi sostanziali rispetto alle terapie esistenti.
HUTCHMED anuncia que su Solicitud de Nueva Droga (NDA) para la combinación de ORPATHYS® y TAGRISSO® ha sido aceptada con estado de revisión prioritaria por la NMPA de China. El tratamiento está dirigido a pacientes con cáncer de pulmón de células no pequeñas, positivo para mutación EGFR y amplificación de MET, que se encuentran en fase localmente avanzada o metastásica, tras la progresión de la enfermedad con la terapia de inhibidores EGFR de primera línea.
La NDA está respaldada por datos del estudio de Fase III SACHI, que evaluó la terapia combinada en comparación con la quimioterapia estándar basada en platino. El estudio cumplió con su objetivo primario de supervivencia libre de progresión en un análisis intermedio planificado. La aceptación activa un pago por hitos de AstraZeneca.
En diciembre de 2024, la NMPA otorgó la designación de Terapia Innovadora a esta combinación, reconociéndola como un nuevo tratamiento potencial que muestra ventajas sustanciales sobre las terapias existentes.
HUTCHMED는 ORPATHYS®와 TAGRISSO®의 조합에 대한 새로운 약물 신청서(NDA)가 중국 NMPA에서 우선 검토 상태로 수락되었다고 발표했습니다. 이 치료법은 1차 EGFR 억제제 요법으로 질병이 진행된 후 MET 증폭이 있는 국소 진행성 또는 전이성 EGFR 돌연변자 양성 비소세포폐암 환자를 대상으로 합니다.
NDA는 플래티넘 기반 이중화학요법에 대한 조합 요법을 평가한 3상 SACHI 시험의 데이터로 지원됩니다. 이 연구는 계획된 중간 분석에서 무진행 생존이라는 주요 목표를 달성했습니다. 수락은 아스트라제네카로부터의 이정표 지급을 촉발합니다.
NMPA는 2024년 12월 이 조합에 대해 중단 치료 지정(Breakthrough Therapy designation)을 부여하여 기존 치료법에 비해 상당한 이점을 보여주는 잠재적 새로운 치료제로 인정했습니다.
HUTCHMED annonce que sa Demande de Médicament Nouveau (NDA) pour la combinaison de ORPATHYS® et TAGRISSO® a été acceptée avec un statut de révision prioritaire par la NMPA de Chine. Le traitement cible les patients atteints de cancer du poumon non à petites cellules, positif pour la mutation EGFR, avec amplification de MET, dans des stades localement avancés ou métastatiques, après progression de la maladie sous une thérapie d'inhibiteurs EGFR de première ligne.
La NDA est soutenue par des données de l'étude de Phase III SACHI, qui a évalué la thérapie combinée par rapport à la chimiothérapie double standard à base de platine. L'étude a atteint son objectif principal de survie sans progression lors d'une analyse intermédiaire planifiée. L'acceptation déclenche un paiement de jalon de la part d'AstraZeneca.
En décembre 2024, la NMPA a accordé la désignation de Thérapie Innovante à cette combinaison, la reconnaissant comme un nouveau traitement potentiel montrant des avantages substantiels par rapport aux thérapies existantes.
HUTCHMED gibt bekannt, dass der Antrag auf Zulassung eines neuen Arzneimittels (NDA) für die Kombination von ORPATHYS® und TAGRISSO® von der NMPA in China mit Prioritätsprüfstatus akzeptiert wurde. Die Behandlung richtet sich an Patienten mit lokal fortgeschrittenem oder metastasiertem EGFR-Mutations-positivem nicht-kleinzelligem Lungenkrebs mit MET-Amplifikation nach Krankheitsfortschritt unter ersterlinie EGFR-Inhibitor-Therapie.
Der NDA wird durch Daten der Phase-III-Studie SACHI unterstützt, die die Kombinationstherapie mit der Standard-Platin-basierten Doppeltchemotherapie verglichen hat. Die Studie erreichte ihren primären Endpunkt der progressionsfreien Überlebenszeit in einer geplanten Zwischenanalyse. Die Akzeptanz löst eine Meilensteinzahlung von AstraZeneca aus.
Die NMPA verlieh dieser Kombination im Dezember 2024 die Bezeichnung Durchbruchtherapie und erkannte sie als potenzielle neue Behandlung mit erheblichen Vorteilen gegenüber bestehenden Therapien an.
- NDA acceptance with priority review status in China
- Phase III SACHI trial met primary endpoint
- Milestone payment triggered from AstraZeneca
- Breakthrough Therapy designation received in December 2024
- None.
Insights
The NDA acceptance with priority review for ORPATHYS® and TAGRISSO® combination represents a significant milestone in targeted lung cancer therapy. The SACHI trial's positive interim analysis, meeting its primary PFS endpoint, validates the combination's efficacy against MET-driven resistance in EGFR-mutated NSCLC.
For simplification: When lung cancer patients receive initial EGFR-targeted therapy but their cancer develops resistance through MET amplification, this new oral combination could provide a more effective, chemotherapy-free alternative to current treatments.
The breakthrough therapy designation and priority review status significantly accelerate the potential market entry, typically reducing the review timeline by several months. This positions HUTCHMED to potentially capture a substantial share of China's EGFR-mutated NSCLC market, estimated to affect 30-40% of Asian NSCLC patients.
This regulatory milestone substantially strengthens HUTCHMED's market position in China's oncology sector. The ORPATHYS®-TAGRISSO® combination addresses a critical unmet need in NSCLC treatment, representing a significant commercial opportunity. The collaboration with AstraZeneca, a global pharmaceutical leader, provides strategic advantages in market penetration and distribution.
In simple terms: This approval process could lead to faster market access for a new cancer treatment, potentially increasing HUTCHMED's revenue through both drug sales and partnership payments. The global development program suggests potential expansion beyond China, multiplying revenue opportunities.
The priority review status typically correlates with accelerated market entry, which could translate to earlier revenue generation. Given the high incidence of EGFR mutations in Asian populations, this positions HUTCHMED to potentially capture a substantial market share in its primary market.
HONG KONG and SHANGHAI and FLORHAM PARK, N.J., Jan. 02, 2025 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (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).
“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
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
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 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
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, locally advanced disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial.
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 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 savolitinib, the further clinical development 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 |
| Media Enquiries | |
| FTI Consulting – | +44 20 3727 1030 / 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 |
| 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 |
| _____________________________________ | |
| REFERENCES | |
| 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. Accessed November 2022. |
| 2 | American Cancer Society. What is Lung Cancer? Available at: 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). |
FAQ
What is the status of HUTCHMED's (HCM) ORPATHYS and TAGRISSO combination NDA in China?
What were the results of HUTCHMED's (HCM) Phase III SACHI trial?
When did HUTCHMED (HCM) receive Breakthrough Therapy designation for ORPATHYS and TAGRISSO?
What is the target patient population for HUTCHMED's (HCM) ORPATHYS-TAGRISSO combination?
What financial benefit does the NDA acceptance bring to HUTCHMED (HCM)?
