REG - Hutchmed China Ltd - Update on Fruquintinib for Gastric Cancer in China

HUTCHMED (China)Announcement

30/08/2024 07:00

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RNS Number : 2958C  Hutchmed (China) Limited  30 August 2024

HUTCHMED Provides Update on Fruquintinib for Second-Line Gastric Cancer in China

 

Hong Kong, Shanghai & Florham Park, NJ - Friday, August 30, 2024: HUTCHMED
(China) Limited ("HUTCHMED (https://www.hutch-med.com/) ") (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HKEX: 13) today announces that it has voluntarily withdrawn its supplemental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
(https://www.hutch-med.com/us-fda-approval-of-fruzaqla-fruquintinib/) and
Europe
(https://www.hutch-med.com/european-commission-approval-for-fruzaqla-fruquintinib/)
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
(https://www.hutch-med.com/nda-acceptance-in-china-for-fruquintinib-combination-with-sintilimab-for-the-treatment-of-advanced-endometrial-cancer/)
status in April 2024, and a Phase III trial in China of fruquintinib in
combination with sintilimab in renal cell carcinoma was fully enrolled
(https://www.hutch-med.com/complete-enrollment-of-china-phase-ii-iii-trial-of-fruquintinib-plus-sintilimab-for-renal-cell-carcinoma/)
in December 2023.

 

About the Phase III FRUTIGA Trial

 

FRUTIGA (NCT03223376 (https://clinicaltrials.gov/ct2/show/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
(https://www.hutch-med.com/wp-content/uploads/2024/06/a240603.pdf) 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 gastro-esophageal 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 (https://jamanetwork.com/journals/jama/fullarticle/2685988) 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
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00772-9/fulltext)
, 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 (https://www.hutch-med.com/) or follow us on LinkedIn
(https://www.linkedin.com/company/hutchmed/) .

 

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 (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  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 (https://gco.iarc.fr/) , Stomach Cancer Fact
Sheet
(https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf) .
 Accessed August 14, 2024.

 3  The Global Cancer Observatory (https://gco.iarc.fr/) , China Fact Sheet
(https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf)
. Accessed August 14, 2024.

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