REG - Hutchmed China Ltd - Japan Approval for FRUZAQLA

HUTCHMED (China)Announcement

24/09/2024 08:00

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RNS Number : 3979F  Hutchmed (China) Limited  24 September 2024

HUTCHMED Announces Japan Approval for FRUZAQLA(®) (fruquintinib) Received by Takeda

 

- Approval based on results from global Phase III FRESCO-2 trial in patients
with previously treated metastatic colorectal cancer -

 

- Fruquintinib already approved in several regions including the United
States, Europe and China -

 

Hong Kong, Shanghai & Florham Park, NJ - Tuesday, September 24, 2024:
HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM:HCM; HKEX:13) today announces that its partner Takeda
(https://www.takeda.com/) (TSE:4502/NYSE:TAK) has received approval from the
Japanese Ministry of Health, Labour and Welfare ("MHLW") to manufacture and
market FRUZAQLA(®) (fruquintinib) for previously treated metastatic
colorectal cancer ("CRC"). FRUZAQLA(®) is the first novel targeted therapy in
Japan to be approved for metastatic CRC, regardless of biomarker status, in
over a decade. CRC is the most prevalent type of cancer in Japan, with an
estimated 161,000 new cases and 54,000 deaths in 2023, according to the
National Cancer Center's statistics. 1  (#_edn1)

 

FRUZAQLA(®) has been approved for the treatment of advanced or recurrent CRC
that is neither curable nor resectable and that has progressed after
chemotherapy.

 

"Takeda has now obtained approval in Japan for FRUZAQLA(®), demonstrating the
strength of our global data package and the potential of this novel medicine
to provide a much-needed treatment option to patients with metastatic CRC,"
said Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of
HUTCHMED. "Takeda has been a leader in metastatic CRC treatment in Japan for
over a decade and we are confident that it is well placed to bring
FRUZAQLA(®) to patients in Japan."

 

Dr. Takayuki Yoshino, Deputy Director of Hospital, Head, Division for the
Promotion of Drug and Diagnostic Development, and Chief, Department of
Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa,
Japan, added: "The approval of FRUZAQLA(®) in Japan is significant news for
patients with metastatic colorectal cancer, who have long needed additional
effective treatment options. The global FRESCO-2 study demonstrated the impact
that this treatment can have on patients in the clinic. The increasing
availability of screening and effective therapies in Japan has been driving
patient outcomes in colorectal cancer, and we hope the introduction of
FRUZAQLA(®) will offer new hope to those with the condition."

 

The approval by the Japanese MHLW was primarily based on results from the
Phase III FRESCO-2 trial conducted in the US, Europe, Japan and Australia.
Data from FRESCO-2 were published
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00772-9/fulltext)
in The Lancet in June 2023. Takeda has the exclusive worldwide license to
further develop, commercialize, and manufacture fruquintinib outside of
mainland China, Hong Kong and Macau. FRUZAQLA(®) was approved in the US in
November 2023 and in Europe in June 2024.

 

About CRC

 

CRC is a cancer that starts in either the colon or rectum. According to the
International Agency for Research on Cancer/World Health Organization, CRC is
the third most prevalent cancer worldwide, associated with more than 1.9
million new cases and 900,000 deaths in 2022. In Japan, CRC was the most
common cancer, with an estimated 146,000 new cases and 60,000 deaths, in
2022.(2) In Europe, CRC was the second most common cancer in 2022, with
approximately 538,000 new cases and 248,000 deaths. 2  (#_edn2) (, 3  (#_edn3)
) In the US, it is estimated that 153,000 patients will be diagnosed with CRC
and 53,000 deaths from the disease will occur in 2024. 4  (#_edn4) Although
early-stage CRC can be surgically resected, metastatic CRC remains an area of
high unmet need with poor outcomes and limited treatment options. Some
patients with metastatic CRC may benefit from personalized therapeutic
strategies based on molecular characteristics; however, most patients have
tumors that do not harbor actionable mutations. 5  (#_edn5) (,) 6  (#_edn6)
(,) 7  (#_edn7) (,) 8  (#_edn8) (,) 9  (#_edn9)

 

About the Phase III FRESCO-2 Trial

 

FRESCO-2 is a multiregional clinical trial conducted in the US, Europe, Japan
and Australia investigating fruquintinib plus best supportive care ("BSC")
versus placebo plus BSC in patients with previously treated metastatic CRC
(NCT04322539 (https://clinicaltrials.gov/ct2/show/NCT04322539) ). FRESCO-2 met
all of its primary and key secondary endpoints, demonstrating statistically
significant and clinically meaningful improvement in overall survival (OS) and
progression-free survival (PFS), with consistent benefit among patients
treated with fruquintinib, regardless of the prior types of therapies they
received. Fruquintinib demonstrated a manageable safety profile in FRESCO-2,
consistent with previously reported fruquintinib monotherapy studies. Adverse
reactions leading to treatment discontinuation occurred in 20% of patients
treated with fruquintinib plus BSC versus 21% of those treated with placebo
plus BSC. Results from the study were presented
(https://oncologypro.esmo.org/meeting-resources/esmo-congress-2022/fresco-2-a-global-phase-iii-multiregional-clinical-trial-mrct-evaluating-the-efficacy-and-safety-of-fruquintinib-in-patients-with-refractory-met)
at the European Society for Medical Oncology Congress (ESMO) in September 2022
and subsequently published
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00772-9/fulltext)
in The Lancet in June 2023. 10  (#_edn10) (, 11  (#_edn11) )

 

About Takeda and FRUZAQLA(®)

 

Takeda has the exclusive worldwide license to further develop, commercialize,
and manufacture fruquintinib outside of mainland China, Hong Kong and Macau,
and markets under the brand name FRUZAQLA(®). FRUZAQLA(®) received approval
in the US
(https://www.hutch-med.com/us-fda-approval-of-fruzaqla-fruquintinib/) in
November 2023, in the EU
(https://www.hutch-med.com/european-commission-approval-for-fruzaqla-fruquintinib/)
in June 2024, in Switzerland in August 2024 and in Canada, Japan and the
United Kingdom in September 2024. The US approval was based on data from two
large, randomized, controlled Phase III trials, the multi-regional FRESCO-2
trial and the FRESCO trial conducted in China, showing consistent benefit
among a total of 734 patients treated with fruquintinib. Safety profiles were
consistent across trials. Regulatory applications are progressing in many
other jurisdictions.

 

About Fruquintinib Approval in China

 

Fruquintinib is approved for marketing in mainland China, Hong Kong and Macau,
where it is co‑marketed by HUTCHMED and Eli Lilly and Company under the
brand name ELUNATE(®). It was included in the China National Reimbursement
Drug List (NRDL) in January 2020. The approvals were based on data from the
FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416
patients with metastatic colorectal cancer in China, which were published
(https://jamanetwork.com/journals/jama/fullarticle/2685988) in The Journal of
the American Medical Association, JAMA. Since its launch in China, over
100,000 patients with colorectal cancer have been treated with fruquintinib.

 

About Fruquintinib

 

Fruquintinib is a selective oral inhibitor of all three VEGF receptors
(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 drug exposure that
achieves sustained target inhibition and flexibility for potential use as part
of a combination therapy. Fruquintinib has demonstrated a manageable safety
profile and is being investigated in combinations with other anti‑cancer
therapies.

 

JAPAN IMPORTANT SAFETY INFORMATION

 

Please consult the FRUZAQLA (fruquintinib) Japan package insert (J-PI) before
prescribing.

 

WARNING: FRUZAQLA should be administered only to patients for whom the use of
FRUZAQLA is considered appropriate under the supervision of a physician with
sufficient knowledge of and experience in cancer chemotherapy at a medical
institution where adequate emergency care can be provided. Prior to treatment
initiation, the efficacy and risks should be fully explained to the patient
and/or his/her family and informed consent should be obtained; Severe
gastrointestinal hemorrhage, including fatal cases, has been reported.
Patients should be carefully monitored, and if any abnormalities are observed,
administration of FRUZAQLA should be withheld and appropriate measures should
be taken. If severe hemorrhage occurs, FRUZAQLA should not be re-administered;
Gastrointestinal perforation has been reported with some fatal cases. Patients
should be carefully monitored, and if any abnormalities are observed,
administration of FRUZAQLA should be withheld and appropriate measures should
be taken. If gastrointestinal perforation occurs, FRUZAQLA should not be
re-administered.

 

CONTRAINDICATIONS: Patients with a history of hypersensitivity to any of the
ingredients of FRUZAQLA.

 

IMPORTANT PRECAUTIONS: Hypertension, including hypertensive crisis, may occur.
Blood pressure should be measured prior to the initiation of FRUZAQLA
treatment and periodically during this treatment; Proteinuria may occur.
Urinary protein should be monitored prior to the initiation of FRUZAQLA
treatment and periodically during this treatment; If a surgical procedure is
to be performed, patients are recommended to withhold FRUZAQLA before the
surgery because wound healing may be delayed. Treatment resumption after the
surgical procedure should be determined depending on the patient's condition
upon confirmation of adequate wound healing.

 

PRECAUTIONS CONCERNING PATIENTS WITH SPECIFIC BACKGROUNDS: Patients with
hyper-ten-sion: Hypertension may worsen; Patients with bleeding diathesis or
abnormal coagulation system: Hemorrhagic events may occur; Patients with
hemorrhage such as gastrointestinal hemorrhage: Hemorrhage may be enhanced;
Patients with a complication of intra-abdominal inflammation in the
gastrointestinal tract, etc.: Gastrointestinal perforation may occur; Patients
with current or a history of thromboembolism: Transient ischaemic attack,
thrombotic microangiopathy, pulmonary embolism, portal vein thrombosis, deep
vein thrombosis, etc. may occur; Patients with severe hepatic impairment
(Child-Pugh Class C): Since FRUZAQLA is metabolized mainly in the liver, blood
concentrations may be increased. There have been no clinical studies conducted
in patients with severe hepatic impairment; Patients with Reproductive
Potential: Women of childbearing potential should be advised to use adequate
contraception during treatment with FRUZAQLA and for 2 weeks after the last
dose; Pregnant Women: FRUZAQLA can be administered to women who are or may be
pregnant only if the expected therapeutic benefits outweigh the possible risks
associated with this treatment. In a rat embryo-fetal toxicity study, fetal
abnormalities and teratogenic effects consisting of fetal external, visceral,
and skeletal malformations and visceral and skeletal variations were observed
at exposure levels approximately 0.05 times the exposure level (AUC) of
FRUZAQLA at the maximum clinical dose (5 mg/day); Breast-feeding Women: It is
advisable not to breastfeed. FRUZAQLA may pass into breast milk, and infants
may experience serious adverse reactions if they are ingested through breast
milk; Pediatric Use: There have been no clinical studies conducted in
pediatric patients.

 

ADVERSE REACTIONS:

 

Any of the adverse reactions listed below may occur. Patients should be
closely monitored, and if any such abnormalities are observed, appropriate
measures should be taken, including treatment discontinuation. Clinically
Significant Adverse Reactions are follows.

 

Hypertension: Hypertension or hypertensive crisis may occur. If an increase in
blood pressure is observed, appropriate treatment such as antihypertensive
drug administration should be given as necessary, and if necessary, the dose
of fruquintinib should be reduced, or fruquintinib administration should be
interrupted. If severe or persistent hypertension, or hypertension that cannot
be controlled by routine antihypertensive therapy occurs or if a hypertensive
crisis occurs, fruquintinib administration should be discontinued; Skin
disorder: Skin disorder including palmar-plantar erythrodysesthesia syndrome
and rash may occur; Hemorrhage: Hemorrhage including epistaxis, hematuria,
gastrointestinal hemorrhage and hemoptysis may occur. Fatal outcomes have been
reported; Gastrointestinal perforation: Fatal outcomes have been reported;
Arterial thromboembolic events: Arterial thromboembolic events including
transient ischemic attack and thrombotic microangiopathy may occur; Venous
thromboembolism events: Venous thromboembolism such as pulmonary embolism,
portal vein thrombosis, and deep vein thrombosis may occur; Posterior
reversible encephalopathy syndrome: If headaches, convulsions, lethargy,
confusion, changes in mental function, blindness or other visual disturbances,
or neurological impairment are observed, fruquintinib administration should be
discontinued, and appropriate measures should be taken, including blood
pressure control; Arterial dissection: Arterial dissection including aortic
dissection may occur.

 

For US Prescribing Information:

https://www.fruzaqla.com/sites/default/files/resources/fruzaqla-prescribing-information.pdf
(https://www.fruzaqla.com/sites/default/files/resources/fruzaqla-prescribing-information.pdf)

 

For European Union Summary of Product Characteristics:

https://www.ema.europa.eu/en/medicines/human/EPAR/fruzaqla
(https://www.ema.europa.eu/en/medicines/human/EPAR/fruzaqla)

 

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 such patients with
CRC 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 approval of fruquintinib
for the treatment of patients with CRC or other indications in other
jurisdictions such as Japan, its potential to gain approvals from regulatory
authorities, the safety profile of fruquintinib, HUTCHMED and/or Takeda's
ability to fund, implement and complete its further clinical development and
commercialization plans for fruquintinib, the timing of these events, each
party's ability to satisfy the terms and conditions under the license
agreement; actions of regulatory agencies, which may affect the initiation,
timing and progress of clinical trials or the regulatory pathway for
fruquintinib; and Takeda's ability to successfully develop and commercialize
fruquintinib. In addition, as certain studies rely on the use of other drug
products 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

 

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 10  (#_ednref10) Dasari NA, et al. LBA25 - FRESCO‑2: A global Phase III
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