TIDMHCM
RNS Number : 9238S
Hutchmed (China) Limited
09 November 2023
HUTCHMED Announces that Takeda Receives U.S. FDA Approval of
FRUZAQLA(TM) (fruquintinib) for Previously Treated Metastatic
Colorectal Cancer
- FRUZAQLA is the first targeted therapy approved in the U.S.
for metastatic colorectal cancer regardless of biomarker status or
prior types of therapies in more than a decade -
- U.S. approval of FRUZAQLA triggers first milestone payment
from Takeda of US$35 million and royalties on net sales -
Hong Kong, Shanghai & Florham Park, NJ - Thursday, November
9, 2023: 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(TM) (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(TM), 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
1. 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.
2. 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.
3. 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.
4. National Cancer Institute. Available at:
https://seer.cancer.gov/statfacts/html/colorect.html (accessed May
2023).
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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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