HUTCHMED (China) Limited (Nasdaq/AIM:HCM, HKEX:13) (“HUTCHMED”)
today announced that its partner Takeda received approval from the
U.S. Food and Drug Administration (“FDA”) for FRUZAQLA™
(fruquintinib), an oral targeted therapy for adults with metastatic
colorectal cancer (“CRC”) who have been previously treated with
fluoropyrimidine-, oxaliplatin‑, and irinotecan‑based chemotherapy,
an anti‑vascular endothelial growth factor (“VEGF”) therapy, and,
if RAS wild‑type and medically appropriate, an anti-epidermal
growth factor receptor (EGFR) therapy. FRUZAQLA is the first and
only selective inhibitor of all three VEGF receptor kinases
approved in the U.S. for previously treated metastatic CRC
regardless of biomarker status.1,2 This approval was received under
Priority Review more than 20 days ahead of the scheduled
Prescription Drug Users Fee Act (PDUFA) date of November 30, 2023.
“This is a landmark moment for metastatic
colorectal cancer patients in the U.S., who will soon have a
much-needed new treatment option that improves survival rates
without negatively impacting their quality of life,” said
Weiguo Su, PhD, Chief Executive Officer and Chief
Scientific Officer of HUTCHMED. “It is also a landmark
moment for HUTCHMED, as we see our first medicine approved outside
of our home market, where we have been improving patient outcomes
with our novel oncology medicines for the last 5 years. In late
2022 we launched a partnership strategy for globalizing our
innovative drug candidates and we are pleased to see early delivery
of this new approach just a year later. This initial success is
thanks to our partner Takeda, who saw the value in fruquintinib,
shared our vision for taking it global, and worked hard with us to
secure U.S. approval. We look forward to continuing our work with
Takeda in an effort to bring FRUZAQLA to patients across the
globe.”
Takeda has the exclusive worldwide license to
further develop, commercialize, and manufacture fruquintinib
outside of mainland China, Hong Kong and Macau. The FDA approval of
FRUZAQLA triggers a US$35 million milestone payment from Takeda.
HUTCHMED will receive royalties on net sales, and is also eligible
to receive potential payments relating to other regulatory,
development and commercial sales milestones. Fruquintinib is
developed and marketed in China by HUTCHMED following approval in
September 2018, under the brand name ELUNATE™, in partnership with
Eli Lilly and Company.
“For more than a decade there has been limited
innovation for patients with metastatic colorectal cancer, one of
the leading causes of cancer death in the U.S.,” said
Teresa Bitetti, President of the Global Oncology Business
Unit at Takeda. “We are proud that our partnership with
HUTCHMED enabled us to bring forth a new option to this patient
population and we look forward to continuing our work for patients
with this underserved cancer.”
The approval of FRUZAQLA is based on data from
two large Phase III trials: the multi-regional FRESCO-2 trial, data
from which were published in The Lancet, along with the FRESCO
trial conducted in China, data from which were published in JAMA,
The Journal of the American Medical Association. The trials
investigated FRUZAQLA plus best supportive care versus placebo plus
best supportive care in patients with previously treated mCRC. 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 FRUZAQLA. Safety profiles were consistent
across trials.
“Metastatic colorectal cancer patients often
present with inoperable disease. As cancer care providers, we must
evaluate and consider treatment options that will improve overall
survival without compromising quality of life,” said Cathy
Eng, M.D., FACP, at Vanderbilt University Medical Center.
“A selective oral anti-VEGF agent with proven benefit in overall
survival and demonstrated a manageable safety profile would be
advantageous for patients by continuing the treatment paradigm of
anti-VEGF therapy at home.”
In the U.S., approximately 153,000 new cases of
CRC will be diagnosed in 2023, representing 7.8% of all new cancer
cases.3,4 Approximately 70% of patients with CRC will experience
metastatic disease, whether at diagnosis or after treatment.
Metastases are the main cause of CRC-related mortality.5,6
The data from FRESCO and FRESCO-2 also supported
the marketing authorization application (“MAA”) for fruquintinib,
which was validated and accepted for review by the European
Medicines Agency (“EMA”) in June 2023. A submission to the Japan
Pharmaceuticals and Medical Devices Agency (“PMDA”) also took place
in September 2023.
About FRUZAQLA
(fruquintinib)
FRUZAQLA (fruquintinib) is a selective oral
inhibitor of VEGFR -1, -2 and -3. VEGFR inhibitors play a pivotal
role in blocking tumor angiogenesis. FRUZAQLA 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.
FRUZAQLA has demonstrated a manageable safety profile and is being
investigated in combinations with other anti-cancer therapies.
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
https://takeda.info/Fruzaqla-Prescribing-Information.
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 2020.7 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 2023.3 In Europe, CRC
was the second most common cancer in 2020, with approximately
520,000 new cases and 245,000 deaths. In Japan, CRC was the most
common cancer, with an estimated 148,000 new cases and 60,000
deaths in 2020.7 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.8,9,10,11,12
About the Phase III FRESCO-2
Trial
The FRESCO-2 study is a multi-regional clinical
trial conducted in the U.S., Europe, Japan and Australia
investigating FRUZAQLA (fruquintinib) plus best supportive care vs
placebo plus best supportive care in patients with previously
treated metastatic CRC (NCT04322539). The study met its primary and
key secondary endpoints, demonstrating that treatment with FRUZAQLA
resulted in statistically significant and clinically meaningful
improvement in overall survival (OS) and progression-free survival
(PFS). The safety profile of FRUZAQLA in FRESCO-2 was consistent
with previously reported FRUZAQLA studies. Results from the study
were presented at the European Society for Medical Oncology (ESMO)
Congress in September 2022 and subsequently published in
The Lancet.13,14
The Phase III FRESCO and FRESCO-2 trials
supported the MAA from the EMA for fruquintinib, which was
validated and accepted for review in June 2023. A submission to the
PMDA also took place in September 2023.
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 oncology drugs now approved and marketed in China. 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 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
approval of a NDA for fruquintinib for the treatment of CRC with
the EMA and the PMDA and the timing of such approvals, the
therapeutic potential of fruquintinib for the treatment of 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 timing and outcome of
clinical studies and the sufficiency of clinical data to support
NDA approval of fruquintinib for the treatment of patients with CRC
or other indications in the E.U., Japan or other jurisdictions, its
potential to gain approvals from regulatory authorities on an
expedited basis or at all; the efficacy and 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; Takeda’s ability to
successfully develop, manufacture and commercialize fruquintinib;
and the impact of COVID-19 on general economic, regulatory and
political conditions. In addition, as certain studies rely on the
use of other drug products such as paclitaxel as combination
therapeutics with fruquintinib, such risks and uncertainties
include assumptions regarding the safety, efficacy, supply and
continued regulatory approval of these therapeutics. Such
forward-looking statements include, without limitation, statements
regarding the plan to develop, manufacture and commercialize
fruquintinib under the license agreement; potential payments under
the license agreement, including any milestone or royalty payments;
potential benefits of the license agreement; and HUTCHMED’s
strategy, goals and anticipated milestones, business plans and
focus. 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 / +1 973 306 4490 /
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 / Daphne Zhang,
Panmure Gordon |
+44 (20) 7886 2500 |
References
- Xu X, et al. Efficacy and safety of
regorafenib and fruquintinib as third-line treatment for colorectal
cancer: a narrative review. Transl Cancer Res 2022;11(1):276-287.
doi: 10.21037/tcr-20-3539.
- Sun Q, et al. (2014) Discovery of
fruquintinib, a potent and highly selective small molecule
inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy,
Cancer Biol Ther. 2014 15:12, 1635-1645. doi:
10.4161/15384047.2014.964087.
- Siegel RL, et al. Colorectal cancer
statistics, 2023 [published online ahead of print, 2023 Mar 1]. CA
Cancer J Clin. 2023; 73(3):233-254. doi:10.3322/caac.21772.
- National Cancer Institute.
Available at: https://seer.cancer.gov/statfacts/html/colorect.html
(accessed May 2023).
- Atreya CE, Yaeger R, Chu E.
Systemic therapy for metastatic colorectal cancer: from current
standards to future molecular targeted approaches. Am Soc Clin
Oncol Educ Book. 2017;37:246-256. doi:10.1200/EDBK_175679.
- Vatandoust S, et al. Colorectal
cancer: Metastases to a single organ. World J Gastroenterol.
2015;21(41):11767-76. doi:10.3748/wjg.v21.i41.11767.
- Sung H, et al. Global Cancer
Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality
Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin.
2021;71(3):209-249. doi:10.3322/caac.21660.
- Bando H, et al. Therapeutic
landscape and future direction of metastatic colorectal cancer. Nat
Rev Gastroenterol Hepatol 2023; 20(5)306-322.
doi:10.1038/s41575-022-00736-1.
- D'Haene N, et al. Clinical
application of targeted next-generation sequencing for colorectal
cancer patients: a multicentric Belgian experience. Oncotarget.
2018;9(29):20761-20768. Published 2018 Apr 17.
doi:10.18632/oncotarget.25099.
- Venderbosch, et al. Mismatch repair
status and braf mutation status in metastatic colorectal cancer
patients: A pooled analysis of the Cairo, Cairo2, coin, and Focus
Studies. Clinical Cancer Res.,2014; 20(20):5322–5330.
doi:10.1158/1078-0432.ccr-14-0332.
- Koopman, M., et al. Deficient
mismatch repair system in patients with sporadic advanced
colorectal cancer. Br J Cancer. 209;100(2), 266–273.
doi:10.1038/sj.bjc.6604867.
- Ahcene Djaballah S, et al. HER2 in
Colorectal Cancer: The Long and Winding Road From Negative
Predictive Factor to Positive Actionable Target. Am Soc Clin Oncol
Educ Book. 2022;42:1-14. doi:10.1200/EDBK_351354.
- Dasari NA, et al. LBA25 – FRESCO-2:
A global phase 3 multiregional clinical trial (MRCT) evaluating the
efficacy and safety of fruquintinib in patients with refractory
metastatic colorectal cancer. Ann Oncol. 2022 Sep;33(suppl_7):
S1391-S1392. doi:10.1016/j.annonc.2022.08.021.
- Dasari NA, et al. Fruquintinib
versus placebo in patients with refractory metastatic colorectal
cancer (FRESCO-2): an international, multicentre, randomised,
double-blind, phase 3 study [published online ahead of print, 2023
Jun 15]. Lancet. 2023. doi: 10.1016/S0140-6736(23)00772-9.
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