HUTCHMED Provides Update on Fruquintinib for Second-Line Gastric Cancer in China
HUTCHMED has voluntarily withdrawn its supplemental New Drug Application (NDA) in China for fruquintinib in combination with paclitaxel for second-line advanced gastric cancer treatment. This decision follows discussions with the National Medical Products Administration of China (NMPA) and an internal review of the data package from the Phase III FRUTIGA study.
While the study showed statistically significant improvements in progression-free survival (PFS) and other endpoints, the overall survival (OS) improvement was not statistically significant. The high proportion of patients receiving subsequent therapies confounded the OS effect, although favorable trends were observed. HUTCHMED remains optimistic about fruquintinib's potential in gastric cancer treatment and will evaluate new paths forward.
HUTCHMED ha ritirato volontariamente la sua domanda supplementare di Nuovo Farmaco (NDA) in Cina per fruquintinib in combinazione con paclitaxel per il trattamento del cancro gastrico avanzato in seconda linea. Questa decisione è stata presa dopo discussioni con l'Amministrazione Nazionale per i Prodotti Medici della Cina (NMPA) e una revisione interna del pacchetto dati dello studio di Fase III FRUTIGA.
Sebbene lo studio abbia mostrato miglioramenti statisticamente significativi nella sopravvivenza libera da progressione (PFS) e in altri endpoint, il miglioramento della sopravvivenza globale (OS) non è risultato statisticamente significativo. L'elevata proporzione di pazienti che ricevono terapie successive ha confuso l'effetto sull'OS, sebbene siano stati osservati trend favorevoli. HUTCHMED rimane ottimista riguardo al potenziale di fruquintinib nel trattamento del cancro gastrico e valuterà nuove strade per il futuro.
HUTCHMED ha retirado voluntariamente su Solicitud Suplementaria de Nuevo Medicamento (NDA) en China para fruquintinib en combinación con paclitaxel para el tratamiento del cáncer gástrico avanzado en segunda línea. Esta decisión sigue a discusiones con la Administración Nacional de Productos Médicos de China (NMPA) y a una revisión interna del paquete de datos del estudio de Fase III FRUTIGA.
Aunque el estudio mostró mejoras estadísticamente significativas en la supervivencia libre de progresión (PFS) y otros criterios de valoración, la mejora en la supervivencia global (OS) no fue estadísticamente significativa. La alta proporción de pacientes que recibieron terapias posteriores confundió el efecto sobre la OS, aunque se observaron tendencias favorables. HUTCHMED sigue siendo optimista sobre el potencial de fruquintinib en el tratamiento del cáncer gástrico y evaluará nuevas formas de avanzar.
HUTCHMED는 중국에서 두 번째 예방선 고급 위암 치료를 위해 paclitaxel과 함께 fruquintinib에 대한 추가 신약 신청(NDA)을 자발적으로 철회했습니다. 이 결정은 중국 국가의약품관리국(NMPA)과의 논의 및 3상 FRUTIGA 연구의 데이터 패키지에 대한 내부 검토 후에 이루어졌습니다.
연구에서 진행 없는 생존 기간(PFS) 및 기타 평가지표에서 통계적으로 유의미한 개선이 나타났지만, 전체 생존 기간(OS)의 개선은 통계적으로 유의미하지 않았습니다. 후속 치료를 받는 환자의 비율이 높아 OS 효과에 혼란을 주었지만, 유리한 경향이 관찰되었습니다. HUTCHMED는 위암 치료에서 fruquintinib의 가능성에 대해 긍정적으로 평가하고 있으며, 새로운 진로를 모색할 것입니다.
HUTCHMED a retiré volontairement sa demande supplémentaire de nouveau médicament (NDA) en Chine pour fruquintinib en combinaison avec le paclitaxel pour le traitement du cancer gastrique avancé en deuxième ligne. Cette décision fait suite à des discussions avec l'Administration nationale des produits médicaux de Chine (NMPA) et à un examen interne du paquet de données de l'étude de Phase III FRUTIGA.
Bien que l'étude ait montré des améliorations statistiquement significatives de la survie sans progression (PFS) et d'autres critères, l'amélioration de la survie globale (OS) n'était pas statistiquement significative. La forte proportion de patients recevant des thérapies ultérieures a compliqué l'effet sur l'OS, bien que des tendances favorables aient été observées. HUTCHMED reste optimiste quant au potentiel de fruquintinib dans le traitement du cancer gastrique et évaluera de nouvelles voies à explorer.
HUTCHMED hat seinen Antrag auf eine ergänzende Zulassung eines neuen Medikaments (NDA) in China für fruquintinib in Kombination mit Paclitaxel zur Behandlung von fortgeschrittenem Magenkrebs in der zweiten Linie freiwillig zurückgezogen. Diese Entscheidung folgte auf Gespräche mit der Nationalen Arzneimittelverwaltung von China (NMPA) und einer internen Überprüfung des Datenpakets der Phase-III FRUTIGA-Studie.
Obwohl die Studie statistisch signifikante Verbesserungen in der progressionsfreien Überlebenszeit (PFS) und anderen Endpunkten zeigte, war die Verbesserung des Gesamtüberlebens (OS) statistisch nicht signifikant. Der hohe Anteil der Patienten, die nachfolgende Therapien erhielten, verwirrte den OS-Effekt, obwohl günstige Trends beobachtet wurden. HUTCHMED bleibt optimistisch hinsichtlich des Potenzials von fruquintinib in der Behandlung von Magenkrebs und wird neue Wege zur Weiterverfolgung prüfen.
- Fruquintinib demonstrated statistically significant improvements in progression-free survival (PFS) and other clinically meaningful endpoints in the Phase III FRUTIGA study
- Fruquintinib plus paclitaxel showed a tolerable safety profile with no new safety signals observed
- Fruquintinib is already approved in China, the US, and Europe for treating metastatic colorectal cancer
- Regulatory applications for fruquintinib in metastatic colorectal cancer are progressing in over a dozen jurisdictions
- An NDA for fruquintinib in combination with sintilimab for endometrial cancer was accepted with priority review status in China in April 2024
- Withdrawal of supplemental NDA for fruquintinib in combination with paclitaxel for second-line advanced gastric cancer in China
- Overall survival (OS) improvement in the Phase III FRUTIGA study was not statistically significant
- Current data package deemed insufficient to support approval for gastric cancer indication in China
Insights
The withdrawal of HUTCHMED's supplemental NDA for fruquintinib in second-line gastric cancer is a significant setback for the company's expansion plans in China. While the FRUTIGA study showed positive results in progression-free survival, the lack of statistical significance in overall survival (OS) has proven to be a critical hurdle.
The confounding factor of subsequent therapies impacting OS data is a common challenge in oncology trials. However, regulatory bodies often prioritize OS as a gold standard endpoint. This decision highlights the stringent requirements of the NMPA, particularly for combination therapies in later-line settings.
Looking ahead, HUTCHMED may need to conduct additional studies or perform more sophisticated analyses to address the NMPA's concerns. The company's commitment to exploring fruquintinib's potential in gastric cancer suggests we may see a redesigned trial or a focus on specific patient subgroups where the drug shows the most promise.
This news is likely to have a negative short-term impact on HUTCHMED's stock price. The gastric cancer market in China represents a significant opportunity and this setback delays potential revenue from this indication. However, investors should note that fruquintinib is already approved for colorectal cancer in major markets, providing a revenue stream.
The company's diverse pipeline, including ongoing trials in endometrial and renal cell carcinoma, offers potential for future growth. The
Key financial metrics to watch include R&D expenses, which may increase if additional studies are required and the performance of fruquintinib in its approved indication to gauge overall commercial potential.
The NMPA's stance on fruquintinib's supplemental NDA underscores the evolving regulatory landscape in China. This decision aligns with a global trend of regulatory bodies demanding robust overall survival data, especially for combination therapies in oncology.
HUTCHMED's proactive withdrawal suggests a strategic approach to avoid a formal rejection. This move allows the company to refine its data package and potentially resubmit with a stronger case. The emphasis on dialogue with the CDE indicates a collaborative regulatory process, which is encouraging for future interactions.
For the industry, this case highlights the importance of early alignment with regulators on endpoints and data interpretation, particularly in complex oncology trials where subsequent therapies can confound survival data. Companies developing cancer therapies for the Chinese market should take note and plan their clinical programs accordingly.
HONG KONG and SHANGHAI and FLORHAM PARK, N.J., Aug. 30, 2024 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it has voluntarily withdrawn its supplemental New Drug Application (“NDA”) in China for fruquintinib in combination with paclitaxel for the treatment of second-line advanced gastric or gastroesophageal junction adenocarcinoma and will evaluate a new route forward. Following an additional internal review of the current data package, in light of recent discussions with the National Medical Products Administration of China (“NMPA”), HUTCHMED has determined that the submission is unlikely to support an approval in China at this time.
This supplemental NDA for fruquintinib was based on data from the Phase III FRUTIGA study, which was declared positive due to a statistically significant improvements in many clinically meaningful endpoints, including progression-free survival (“PFS”), which served as one of two primary endpoints. However, while an improvement was also observed in the second primary endpoint of median overall survival (“OS”), it was not statistically significant. Extensive subsequent analyses conducted indicate that, although the high and imbalanced proportion of patients receiving subsequent antitumor therapies confounded the OS effect, fruquintinib plus paclitaxel demonstrated meaningful clinical benefit and favorable OS trends through a variety of models. Furthermore, no new safety signals were observed, and fruquintinib plus paclitaxel showed a tolerable safety profile. However, it became clear from dialogue with the Centre for Drug Evaluation (CDE) of the NMPA and its external committee members that the current understanding and interpretation of the OS results could not serve as the basis of the supplemental NDA approval, and that further work needs to be undertaken.
Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, commented, “Whilst disappointed by this outcome, we remain optimistic about the utility of fruquintinib in the treatment of gastric cancer. The data set from FRUTIGA demonstrates that fruquintinib plus paclitaxel could offer a promising new treatment option to certain patients in future, and we are driven to investigate this possibility thoroughly. We look forward to evaluating a path forward and would like to thank both the patients and principal investigators who took part in this study for contributing to a better understanding of this devastating disease.”
Dr Rui-Hua Xu, Professor at the Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, added, “Gastric cancer is the fifth most common cancer worldwide and patients in China are currently underserved by available treatment options. Although the current data package would not support approval on this occasion, the Phase III study demonstrated clear benefits of this fruquintinib combination across many clinically meaningful endpoints and the team are committed to evaluating all options. Promising subgroup analyses are helping us to better understand how we can effectively combat this disease, and we remain hopeful that this study forms part of an important journey to a much-needed new therapy.”
Fruquintinib is approved in China, the US and Europe for the treatment of previously-treated patients with metastatic colorectal cancer (“CRC”), and regulatory applications for this indication are progressing as expected in over a dozen jurisdictions. It works as an anti-cancer therapy by blocking tumor angiogenesis, a proliferation of blood vessels that is critical for cancer growth. It is a selective oral inhibitor of vascular endothelial growth factor receptors (“VEGFRs”) 1, 2 and 3, and this pathway plays a key role in the pathogenesis of many solid tumors including gastric cancer.
An NDA in China for fruquintinib in combination with sintilimab in endometrial cancer was accepted with priority review status in April 2024, and a Phase III trial in China of fruquintinib in combination with sintilimab in renal cell carcinoma was fully enrolled in December 2023.
About the Phase III FRUTIGA Trial
FRUTIGA (NCT03223376) was a 1:1 randomized, double-blind, Phase III study conducted across 35 sites in China. It evaluated fruquintinib in combination with paclitaxel chemotherapy, compared with paclitaxel monotherapy, for second-line treatment in 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma. The study was declared positive due to a statistically significant improvement in progression-free survival (“PFS”), one of two dual primary endpoints. Median PFS for patients who received fruquintinib plus paclitaxel was 5.6 months, compared to 2.7 months for those who received paclitaxel monotherapy (stratified hazard ratio [“HR”] = 0.569; p < 0.0001). An improvement was also observed in the dual primary endpoint of median overall survival (OS), (9.6 months vs. 8.4 months) but this was not statistically significant. Fruquintinib plus paclitaxel demonstrated statistically significant improvements in multiple other endpoints including objective response rate (ORR), disease control rate (DCR) and duration of response (DoR). It was well tolerated, with a safety profile consistent with expectations and previously reported studies.1
Results were published in Nature Medicine and presented at the ASCO 2024 Annual Meeting, concluding that fruquintinib plus paclitaxel could be a promising second-line treatment option for patients with advanced gastric or gastroesophageal adenocarcinoma, who have failed fluoropyrimidine- or platinum-containing chemotherapy.
About Gastric Cancer
Gastric cancer is a cancer that starts in the stomach. It is the fifth most common cancer worldwide in 2022. It was estimated to have caused approximately 660,000 deaths worldwide.2 In China, it was estimated that over 359,000 people were diagnosed with gastric cancer, and approximately 260,000 people died from gastric cancer.3
About Fruquintinib
Fruquintinib is a selective oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for the potential use as part of combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti-cancer therapies.
About Fruquintinib Approval for metastatic CRC in China
Fruquintinib is approved for marketing in China, where it is co-marketed by HUTCHMED and Lilly under the brand name ELUNATE®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. The approval was based on data from the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, which were published in The Journal of the American Medical Association, JAMA. Since its launch, fruquintinib has benefited over 100,000 patients in China.
About Takeda and Fruquintinib Approval for metastatic CRC outside China
Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau. For the treatment of metastatic CRC, fruquintinib received approval in the US in November 2023 and in Europe in June 2024, where it is marketed by Takeda under the brand name FRUZAQLA®. The approvals were based on data from two large, randomized, controlled Phase III trials: the multi-regional FRESCO-2 trial, data from which were published in The Lancet, and the FRESCO trial conducted in China. The trials investigated fruquintinib plus best supportive care versus placebo plus best supportive care in patients with previously treated metastatic CRC. Both FRESCO and FRESCO-2 met their primary and key secondary efficacy endpoints and showed consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Other regulatory applications for this indication are progressing as expected in Japan and in many other jurisdictions.
About HUTCHMED
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and 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 it 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 US and Europe. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.
Forward-Looking Statements
This announcement 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, including its expectations regarding the therapeutic potential of fruquintinib for the treatment of patients with advanced gastric cancer and the further clinical development of fruquintinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of clinical data to support NDA approval of fruquintinib for the treatment of patients with advanced gastric cancer in China, the US, Europe, Japan, Australia or other jurisdictions, its potential to gain expeditious approvals from regulatory authorities, the safety profile of fruquintinib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib. In addition, as certain studies rely on the use of other drug products such as paclitaxel, tislelizumab and sintilimab as combination therapeutics with fruquintinib, 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, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise.
Medical Information
This announcement 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.
Inside Information
This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).
CONTACTS
| Investor Enquiries | +852 2121 8200 / 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 |
| Zhou Yi, Brunswick | +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com |
| Nominated Advisor | |
| Atholl Tweedie / Freddy Crossley / Rupert Dearden, Panmure Liberum | +44 (20) 7886 2500 |
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| 1 | Wang F, et al. Fruquintinib plus paclitaxel versus placebo plus paclitaxel as second-line therapy for advanced gastric or gastro-esophageal junction adenocarcinoma (FRUTIGA): a randomized, multicenter, double-blind, placebo-controlled, phase 3 study [published online ahead of print, 2024 Jun 1]. Nat Med. 2024. DOI: 10.1038/s41591-024-02989-6. |
| 2 | The Global Cancer Observatory, Stomach Cancer Fact Sheet. Accessed August 14, 2024. |
| 3 | The Global Cancer Observatory, China Fact Sheet. Accessed August 14, 2024. |
FAQ
Why did HUTCHMED withdraw the supplemental NDA for fruquintinib in gastric cancer?
What were the results of the Phase III FRUTIGA study for fruquintinib (HCM)?
Is fruquintinib (HCM) approved for any indications?
What other indications is HUTCHMED pursuing for fruquintinib (HCM)?
