REG - Hutchmed China Ltd - European Commission Approval for FRUZAQLA

HUTCHMED (China)Announcement

24/06/2024 07:00

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RNS Number : 4632T  Hutchmed (China) Limited  24 June 2024

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

 

- Approval for previously treated metastatic colorectal cancer based on
results from positive, global, Phase III FRESCO-2 Trial -

 

- FRUZAQLA(®) (fruquintinib) is the first novel targeted therapy in the EU
for metastatic colorectal cancer regardless of biomarker status in over a
decade -

 

Hong Kong, Shanghai & Florham Park, NJ - Friday, June 21, 2024: HUTCHMED
(China) Limited ("HUTCHMED (https://www.hutch-med.com/) ") (Nasdaq/AIM:HCM;
HKEX:13) today announces that its partner Takeda
(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.takeda.com%2Finvestors%2F&esheet=52286207&newsitemid=20200915005224&lan=en-US&anchor=TSE%3A4502%2FNYSE%3ATAK&index=2&md5=b7076f2bbb02ad331cdf76657f8aa07f)
(TSE:4502/NYSE:TAK) has received notification from the European Commission
("EC") that it has approved FRUZAQLA(®) (fruquintinib) as a monotherapy
indicated for the treatment of adult patients with metastatic colorectal
cancer ("CRC") who have been previously treated with available standard
therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based
chemotherapies, anti-VEGF agents, and anti-EGFR agents, and who have
progressed on or are intolerant to treatment with either
trifluridine-tipiracil or regorafenib.

 

"With fruquintinib being the first and only selective inhibitor of all three
VEGFRs to be approved in the EU for colorectal cancer, this decision
represents a significant milestone in European oncology," added Josep
Tabernero, MD, PhD, director of Vall d´Hebron Institute of Oncology (VHIO).
"There is a clear need in Europe for patients and their clinicians to be able
to access a new treatment option for previously treated metastatic colorectal
cancer, and we are excited that this important step has been taken so that we
can begin prescribing this new and differentiated medicine."

 

"We are delighted to have achieved EC approval for FRUZAQLA(®) and that we
can now offer a new therapeutic option for patients with previously treated
metastatic colorectal cancer, regardless of their biomarker status," said
Teresa Bitetti, President of the Global Oncology Business Unit at Takeda.
"Patients in Europe with metastatic colorectal cancer have long needed
additional treatment options, and we are grateful to be able to meet that need
thanks to our partnership with HUTCHMED."

 

"This is a significant milestone for HUTCHMED, as it is the first product from
our research and discovery engine to be approved in Europe, achieved through
our partnership with Takeda to make this possible in such a short period of
time," added Weiguo Su, PhD, Chief Executive Officer and Chief Scientific
Officer of HUTCHMED. "This novel oncology medicine is currently improving the
treatment outlook in the U.S. and China, and we look forward to seeing its
impact for patients across Europe."

 

The EC's approval has been granted following a positive opinion
(https://www.hutch-med.com/positive-chmp-opinion-for-fruquintinib-in-mcrc/)
from the Committee for Medicinal Products for Human Use ("CHMP") in April
2024. The CHMP's opinion was primarily based on results from the Phase III
multiregional FRESCO-2 trial, which supported the Marketing Authorisation
Application ("MAA") that was validated and accepted for review
(https://www.hutch-med.com/fruquintinib-ema-validation/) in June 2023. 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.

 

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 Europe, CRC was the second
most common cancer in 2022, with approximately 538,000 new cases and 248,000
deaths. 1  (#_edn1) (, 2  (#_edn2) ) In the U.S., it is estimated that 153,000
patients will be diagnosed with CRC and 53,000 deaths from the disease will
occur in 2024. 3  (#_edn3) In Japan, CRC was the most common cancer, with an
estimated 146,000 new cases and 60,000 deaths, in 2022.(2) 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. 4  (#_edn4) (,) 5  (#_edn5)
(,) 6  (#_edn6) (,) 7  (#_edn7) (,) 8  (#_edn8)

 

About the Phase III FRESCO-2 Trial

 

FRESCO-2 is a multiregional clinical trial conducted in the U.S., 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. 9  (#_edn9) (, 10  (#_edn10) )

 

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 high drug exposure,
sustained target inhibition, and flexibility for its 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.

 

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.
Fruquintinib received approval in the U.S.
(https://www.hutch-med.com/us-fda-approval-of-fruzaqla-fruquintinib/) in
November 2023, where it is marketed by Takeda under the brand name
FRUZAQLA(®). The U.S. 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.

 

In addition to the submission to the EMA, a submission to the Japan
Pharmaceuticals and Medical Devices Agency (PMDA) took place in September
2023.

 

About Fruquintinib Approval in China

 

Fruquintinib is approved for marketing in China, 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 approval was 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 and as of
mid‑2023, more than 80,000 patients with colorectal cancer have been treated
with fruquintinib.

 

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 U.S. 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/) .

 

E.U. IMPORTANT SAFETY INFORMATION

 

Please consult the FRUZAQLA (fruquintinib) Summary of Product Characteristics
(SmPC) before prescribing.

 

Guidance for use: FRUZAQLA should be initiated by a physician experienced in
the administration of anticancer therapy. Patients should be given the package
leaflet.

 

CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the
excipients.

 

SPECIAL POPULATIONS: Renal impairment: No dose adjustment is required for
patients with mild, moderate, or severe renal impairment; Hepatic impairment:
No dose adjustment is required for patients with mild or moderate hepatic
impairment. FRUZAQLA is not recommended for use in patients with severe
hepatic impairment as FRUZAQLA has not been studied in this population;
Elderly: No dose adjustment is required in patients aged 65 years or above;
Paediatric population: There is no relevant use of FRUZAQLA in the paediatric
population for the indication of metastatic colorectal cancer; Women of
childbearing potential/Contraception in females: Women of childbearing
potential should be advised to use highly effective contraception during
treatment and for at least 2 weeks following the last dose of FRUZAQLA;
Pregnancy: There are no clinical data available on the use of FRUZAQLA in
pregnant women. Based on its mechanism of action, FRUZAQLA has the potential
to cause foetal harm. Animal studies have shown reproductive toxicity,
including foetal malformations. FRUZAQLA should not be used during pregnancy
unless the clinical condition of the woman requires treatment with FRUZAQLA.
If FRUZAQLA is used during pregnancy or if the patient becomes pregnant while
on treatment, the patient must be informed of the potential hazard to the
foetus; Breast-feeding: The safe use of FRUZAQLA during breast-feeding has not
been established. It is not known whether FRUZAQLA or its metabolites are
excreted in human milk. There are no animal data on the excretion of FRUZAQLA
in animal milk. A risk to the breastfeeding newborns/infants cannot be
excluded. Breastfeeding should be discontinued during treatment and for 2
weeks after the last dose; Fertility: There are no data on the effects of
FRUZAQLA on human fertility. Results from animal studies indicate that
FRUZAQLA may impair male and female fertility.

 

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

 

·  Hypertension: Hypertension, including hypertensive crisis, has been
reported in patients treated with FRUZAQLA. Pre-existing hypertension should
be monitored and adequately controlled in accordance with standard medical
practices before starting FRUZAQLA treatment.

 

Hypertension should be medically managed with antihypertensive medicinal
products and adjustment of the FRUZAQLA dose, if necessary. FRUZAQLA should be
permanently discontinued for hypertension that cannot be controlled with
antihypertensive therapy or in patients with hypertensive crisis.

 

·  Haemorrhagic events: Haemorrhagic events have been reported in patients
treated with FRUZAQLA, including gastrointestinal (GI) tract events. Serious
and sometimes fatal bleeding events have been reported in patients after
treatment with FRUZAQLA.

 

Haematologic and coagulation profiles should be monitored in accordance with
standard medical practices in patients at risk for bleeding, including those
treated with anticoagulants or other concomitant medicinal products that
increase the risk of bleeding. In the event of severe bleeding requiring
immediate medical intervention, FRUZAQLA should be permanently discontinued.

 

·  Gastrointestinal perforation: GI perforation events, including fatal
events, have been reported in patients treated with FRUZAQLA.

 

Symptoms of GI perforation should be periodically monitored during treatment
with FRUZAQLA.

 

FRUZAQLA should be permanently discontinued in patients developing GI
perforation.

 

·  Proteinuria: Proteinuria events have occurred in patients treated with
FRUZAQLA.

 

Proteinuria should be monitored before initiation and during treatment with
FRUZAQLA in accordance with standard medical practices. If urine dipstick
proteinuria ≥ 2 g / 24 hours is detected, dose interruptions, adjustments,
or discontinuation may be necessary. FRUZAQLA should be permanently
discontinued in patients developing nephrotic syndrome.

 

·  Palmar-plantar erythrodysaesthesia syndrome (PPES): PPES is the most
frequently reported dermatological adverse reaction.

 

If Grade ≥2 skin reactions are detected, dose interruptions, adjustments, or
discontinuation may be necessary.

 

·  Posterior reversible encephalopathy syndrome (PRES): PRES has been
reported in 1 patient (0.1%) treated with FRUZAQLA in clinical studies. PRES
is a rare neurologic disorder that can present with headache, seizure,
lethargy, confusion, altered mental function, blindness, and other visual or
neurological disturbances, with or without associated hypertension. A
diagnosis of PRES requires confirmation by brain imaging, preferably magnetic
resonance imaging (MRI). In patients developing PRES, discontinuation of
FRUZAQLA, along with control of hypertension and supportive medical management
of other symptoms, are recommended.

 

·  Impaired wound healing: Impaired wound healing has been reported in 1
patient (0.1%) treated with FRUZAQLA in clinical studies.

 

Patients are recommended to withhold FRUZAQLA for at least 2 weeks prior to
surgery. FRUZAQLA should not be resumed for at least 2 weeks after surgery, as
clinically indicated when there is evidence of adequate wound healing.

 

·  Arterial and venous thromboembolic events: It is recommended to avoid
starting treatment with FRUZAQLA in patients with a history of thromboembolic
events (including deep vein thrombosis and pulmonary embolism) within the past
6 months or if they have a history of stroke and/or transient ischemic attack
within the last 12 months. If arterial thrombosis is suspected, FRUZAQLA
should be discontinued immediately.

 

INTERACTIONS

 

Effects of other medicinal products on the pharmacokinetics of FRUZAQLA

 

CYP3A inducers

 

Co-administration of FRUZAQLA with rifampicin (a strong CYP3A inducer) 600 mg
once daily decreased FRUZAQLA AUC(inf) by 65% and decreased C(max) by 12%. The
concomitant use of FRUZAQLA with strong and moderate CYP3A inducers should be
avoided.

 

CYP3A inhibitors

 

Co-administration of FRUZAQLA with itraconazole (a strong CYP3A inhibitor) 200
mg twice daily did not result in clinically meaningful changes in the area
under the concentration-time curve (AUC) and C(max) of FRUZAQLA. No dose
adjustment of FRUZAQLA is needed during concomitant use with CYP3A inhibitors.

 

Gastric acid lowering agents

 

Co-administration of FRUZAQLA with rabeprazole (a proton pump inhibitor) 40 mg
once daily did not result in clinically meaningful changes in the AUC of
FRUZAQLA. No dose adjustment of FRUZAQLA is needed during concomitant use with
gastric acid lowering agents.

 

Effect of FRUZAQLA on the pharmacokinetics of other medicinal products

 

Medicinal products that are substrates of P-glycoprotein (P-gp)

 

Co-administration of a single dose of dabigatran etexilate 150 mg (a P-gp
substrate) with a single dose of FRUZAQLA 5 mg decreased AUC of dabigatran by
9%. No dose adjustment is recommended for P-gp substrates during concomitant
use with FRUZAQLA.

 

Medicinal products that are substrates of breast cancer resistance protein
(BCRP)

 

Co-administration of a single 10 mg dose of rosuvastatin (a BCRP substrate)
with a single 5 mg dose of FRUZAQLA decreased AUC of rosuvastatin by 19%. No
dose adjustment is recommended for BCRP substrates during concomitant use with
FRUZAQLA.

 

UNDESIRABLE EFFECTS: The most commonly reported adverse reactions with
FRUZAQLA are:

 

 Very common              Thrombocytopenia, hypothyroidism, anorexia, hypertension, dysphonia,

                        diarrhoea, stomatitis, aspartate aminotransferase increased, total bilirubin
 (frequency ≥1/10)        increased, alanine aminotransferase increased, palmar-plantar
                          erythrodysaesthesia syndrome, musculoskeletal discomfort, arthralgia,
                          proteinuria, asthenia, and fatigue
 Common                   Pneumonia, upper respiratory tract infection, bacterial infections,

                        leukopenia, neutropenia, hypokalemia, epistaxis, throat pain, gastrointestinal
 (≥1/100 to <1/10)        haemorrhage, gastrointestinal perforation, pancreatic enzymes increased, oral
                          pain, rash, and mucosal inflammation

 

Forward‑Looking Statements

 

This announcement 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 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 U.S. 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 Gordon      +44 (20) 7886 2500

 

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