HUTCHMED Announces Positive CHMP Opinion for Fruquintinib in
Previously Treated Metastatic Colorectal Cancer Received by
Takeda
- If approved in the European Union, fruquintinib
will be the first novel targeted therapy for metastatic colorectal
cancer regardless of biomarker status in over a decade -
- Positive opinion based on results from FRESCO‑2
Phase III clinical trial -
Hong Kong, Shanghai
& Florham Park, NJ - Friday, April 26, 2024: HUTCHMED
(China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM;
HKEX:13) today announces that its partner
Takeda (TSE:4502/NYSE:TAK) received notification that the
Committee for Medicinal Products for Human Use ("CHMP") of the
European Medicines Agency ("EMA") has recommended the approval of
fruquintinib for the treatment of adult patients with previously
treated metastatic colorectal cancer ("CRC").
The European Commission (EC) will consider the CHMP
positive opinion when determining the potential marketing
authorization for fruquintinib for metastatic CRC throughout the
European Union ("EU"), Norway, Liechtenstein and Iceland. If
approved, fruquintinib will be the first and only selective
inhibitor of all three vascular endothelial growth factor receptors
("VEGFR") approved in the EU for previously treated metastatic
CRC.[1],[2] Takeda has the exclusive worldwide license to
further develop, commercialize, and manufacture fruquintinib
outside of mainland China, Hong Kong and Macau.
"Through our partnership with HUTCHMED, we have made
strides in expanding access to fruquintinib to eligible patients.
With this positive CHMP opinion for fruquintinib, we are one step
closer to potentially offering patients in the EU an oral,
chemotherapy‑free option that can provide a significant survival
benefit," said Awny Farajallah,
M.D., Chief Medical Officer, Oncology at Takeda. "We look
forward to the European Commission's official decision in the near
future."
"HUTCHMED has a strong track record of developing
innovative oncology medicines for patients in need. People living
with metastatic CRC in the EU currently have limited treatment
options available to them, which can lead to poor outcomes. We are
pleased with our partner Takeda's progress toward redefining the
treatment landscape and helping to address a significant unmet need
for those affected by metastatic CRC in Europe," said Weiguo Su, PhD, Chief Executive Officer and
Chief Scientific Officer of HUTCHMED. "This novel oncology
medicine has had a profound impact for patients in China over the
last five years. Since entering our partnership with Takeda we have
seen this impact extended with its approval and launch in the U.S.
and, pending approval by the European Commission, we look forward
to the medicine having a positive effect for patients in Europe
too."
The CHMP's positive opinion was primarily based on
results from the Phase III multi‑regional FRESCO‑2 trial, which supported the Marketing Authorisation
Application ("MAA"). The MAA was validated
and accepted for review by the EMA 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, CRC is the third most prevalent cancer worldwide,
associated with more than 935,000 deaths in 2020. In Europe, CRC
was the second most common cancer in 2020, with approximately
520,000 new cases and 245,000 deaths.[3] 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.[4] In Japan, CRC was the most common
cancer, with an estimated 148,000 new cases and 60,000 deaths, in
2020.3 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],[6],[7],[8],[9]
About the Phase III FRESCO‑2 Trial
FRESCO‑2 is a multi‑regional 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 mCRC (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 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 at the European Society for Medical Oncology Congress
(ESMO) in September 2022 and subsequently
published in The Lancet in June
2023.[10],[11]
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 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. 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
in The Journal of the American Medical Association, JAMA. Since its launch in China and as
of mid‑2023, more than 80,000 colorectal cancer patients 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 or follow us on
LinkedIn.
U.S. IMPORTANT SAFETY
INFORMATION
WARNINGS AND
PRECAUTIONS
· Hypertension
occurred in 49% of 911 patients with mCRC treated
with FRUZAQLA, including Grade 3-4 events in 19%, and hypertensive
crisis in three patients (0.3%). Do not initiate FRUZAQLA unless
blood pressure is adequately controlled. Monitor blood pressure
weekly for the first month and at least monthly thereafter as
clinically indicated. Initiate or adjust anti-hypertensive therapy
as appropriate. Withhold, reduce dose, or permanently discontinue
FRUZAQLA based on severity of hypertension.
· Hemorrhagic
Events including serious, fatal
events can occur with FRUZAQLA. In 911 patients with mCRC treated
with FRUZAQLA, 6% of patients experienced gastrointestinal
hemorrhage, including 1% with a Grade ≥3 event and 2 patients
with fatal hemorrhages. Permanently discontinue FRUZAQLA in
patients with severe or life-threatening hemorrhage. Monitor the
International Normalized Ratio (INR) levels in patients receiving
anticoagulants.
· Infections.
FRUZAQLA can increase the risk of infections,
including fatal infections. In 911 patients with mCRC treated with
FRUZAQLA, the most common infections were urinary tract infections
(6.8%), upper respiratory tract infections (3.2%) and pneumonia
(2.5%); fatal infections included pneumonia (0.4%), sepsis (0.2%),
bacterial infection (0.1%), lower respiratory tract infection
(0.1%), and septic shock (0.1%). Withhold FRUZAQLA for Grade 3 or 4
infections, or worsening infection of any grade. Resume FRUZAQLA at
the same dose when the infection has resolved.
· Gastrointestinal
Perforation occurred in patients
treated with FRUZAQLA. In 911 patients with mCRC treated with
FRUZAQLA, 1.3% experienced a Grade ≥3 gastrointestinal perforation,
including one fatal event. Permanently discontinue FRUZAQLA in
patients who develop gastrointestinal perforation or
fistula.
· Hepatotoxicity. FRUZAQLA can
cause liver injury. In 911 patients with mCRC treated with
FRUZAQLA, 48% experienced increased ALT or AST, including
Grade ≥3 events in 5%, and fatal events in 0.2% of patients.
Monitor liver function tests (ALT, AST, and bilirubin) before
initiation and periodically throughout treatment with FRUZAQLA.
Temporarily hold and then reduce or permanently discontinue
FRUZAQLA depending on the severity and persistence of
hepatotoxicity as manifested by elevated liver function
tests.
· Proteinuria.
FRUZAQLA can cause proteinuria.
In 911 patients with mCRC treated with FRUZAQLA,
36% experienced proteinuria and 2.5% of patients experienced Grade
≥3 events. Monitor for proteinuria before initiation and
periodically throughout treatment with FRUZAQLA. For proteinuria
≥2g/24 hours, withhold FRUZAQLA until improvement to
≤Grade 1 proteinuria and resume FRUZAQLA at a reduced dose.
Discontinue FRUZAQLA in patients who develop nephrotic
syndrome.
· Palmar-Plantar
Erythrodysesthesia (PPE) occurred in
35% of 911 patients treated with FRUZAQLA, including 8% with
Grade 3 events. Based on severity of PPE, withhold FRUZAQLA
and then resume at the same or reduced dose.
· Posterior Reversible
Encephalopathy Syndrome (PRES), a
syndrome of subcortical vasogenic edema diagnosed by characteristic
finding on MRI, occurred in one of 911 patients treated with
FRUZAQLA. Perform an evaluation for PRES in any patient presenting
with seizures, headache, visual disturbances, confusion, or altered
mental function. Discontinue FRUZAQLA in patients who develop
PRES.
· Impaired Wound
Healing. In 911 patients with mCRC
treated with FRUZAQLA, 1 patient experienced a Grade 2
event of wound dehiscence. Do not administer FRUZAQLA for at least
2 weeks prior to major surgery. Do not administer FRUZAQLA for
at least 2 weeks after major surgery and until adequate wound
healing. The safety of resumption of FRUZAQLA after resolution of
wound healing complications has not been established.
· Arterial Thromboembolic
Events. In 911 patients with mCRC
treated with FRUZAQLA, 0.8% of patients experienced an arterial
thromboembolic event. Initiation of FRUZAQLA in patients with a
recent history of thromboembolic events should be carefully
considered. In patients who develop arterial thromboembolism,
discontinue FRUZAQLA.
· Allergic Reactions to
FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset
Yellow FCF). FRUZAQLA 1 mg
capsules contain FD&C Yellow No. 5 (tartrazine), which may
cause allergic-type reactions (including bronchial asthma) in
certain susceptible persons. FRUZAQLA 1 mg contains FD&C
Yellow No. 6 (sunset yellow FCF), which may cause allergic
reactions.
· Embryo-Fetal
Toxicity. Based on findings in
animal studies and its mechanism of action, FRUZAQLA can cause
fetal harm when administered to pregnant women. Advise pregnant
women of the potential risk to a fetus. Advise females of
childbearing potential and males with female partners of
childbearing potential to use effective contraception during
treatment with FRUZAQLA and for 2 weeks after the last
dose.
ADVERSE REACTIONS
The most common adverse reactions
(incidence ≥20%) following treatment with FRUZAQLA included
hypertension, palmar-plantar erythrodysesthesia (hand-foot skin
reactions), proteinuria, dysphonia, abdominal pain, diarrhea, and
asthenia.
DRUG
INTERACTIONS: Avoid concomitant
administration of FRUZAQLA with strong or moderate CYP3A
inducers.
USE IN SPECIFIC
POPULATIONS
·
Lactation: Advise women not to
breastfeed during treatment with FRUZAQLA and for 2 weeks
after the last dose.
To report SUSPECTED ADVERSE
REACTIONS, contact Takeda Pharmaceuticals at 1-844-662-8532 or the
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see FRUZAQLA (fruquintinib)
full Prescribing
Information.
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
review of a MAA for fruquintinib for the treatment of patients with
CRC with the EMA and the timing of such review, 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 MAA approval of fruquintinib for the treatment of patients
with CRC or other indications in the EU or other jurisdictions such
as Japan, its potential to gain 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, 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
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+852 2121 8200 / ir@hutch‑med.com
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Media Enquiries
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Ben Atwell / Alex Shaw,
FTI Consulting
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+44 20 3727 1030 /
+44 7771 913 902 (Mobile) /
+44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com
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Zhou Yi, Brunswick
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+852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com
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Nominated Advisor
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Atholl Tweedie / Freddy
Crossley / Daphne Zhang, Panmure Gordon
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+44 (20) 7886 2500
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