RCS - Hutchmed China Ltd - HUTCHMED to Receive Milestone Payment from Takeda

HUTCHMED (China)Announcement

13/12/2024 07:00

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RNS Number : 8797P  Hutchmed (China) Limited  13 December 2024

Press Release

 

HUTCHMED to Receive Milestone Payment from Takeda following First European Reimbursement for FRUZAQLA(®) (fruquintinib)

 

- US$10 million milestone payment to HUTCHMED follows first national
reimbursement in Europe -

 

- Follows June 2024 European approval of FRUZAQLA(®) (fruquintinib), the
first novel oral targeted therapy in the EU for metastatic colorectal cancer
regardless of biomarker status in over a decade -

 

Hong Kong, Shanghai & Florham Park, NJ - Friday, December 13, 2024:
HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM:HCM; HKEX:13) today announces that it will receive a US$10 million
milestone payment by its partner Takeda (https://www.takeda.com/)
(TSE:4502/NYSE:TAK). Takeda received a national reimbursement recommendation
for FRUZAQLA(®) (fruquintinib) for patients with previously treated
 metastatic colorectal cancer ("CRC") in Spain in December 2024, the first
national reimbursement recommendation in Europe. CRC is the second most common
cause of cancer-related deaths in Europe.

 

FRUZAQLA(®) was approved by the European Commission ("EC") of the European
Union ("EU") in June 2024. Takeda has the exclusive worldwide license to
further develop, commercialize and manufacture fruquintinib outside of
mainland China, Hong Kong and Macau.

 

"We are delighted for both our partner, Takeda, and patients in Spain who will
now be able to receive reimbursement for this innovative treatment. This is an
important step forward in improving patient access across Europe more
broadly," said Dr Weiguo Su, Chief Executive Officer and Chief Scientific
Officer of HUTCHMED. "It also underscores our ongoing collaboration with
Takeda and reinforces our shared commitment to addressing the needs of
patients with metastatic colorectal cancer."

 

The approvals by the EC were primarily based on results from the Phase III
multiregional FRESCO-2 trial. 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. FRUZAQLA(®) was approved 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, in Canada, Japan
(https://www.hutch-med.com/japan-approval-for-fruzaqla-fruquintinib/) and the
United Kingdom in September 2024 and in Argentina, Australia and Singapore in
October 2024. Regulatory applications are progressing in many other
jurisdictions.

 

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 (, 2 ) 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. 3 
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 (,) 5 (,) 6 (,) 7 (,) 8 

 

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.

 

About Fruquintinib Approvals

 

Global regulatory submissions are based on data from two large, randomized,
controlled Phase III trials, the global, 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. Results from the FRESCO-2 trial were published
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00772-9/fulltext)
in The Lancet in June 2023,  9  while results from the FRESCO trial were
published (https://jamanetwork.com/journals/jama/fullarticle/2685988) in The
Journal of the American Medical Association, JAMA. 10 

 

In mainland China, Hong Kong and Macau, fruquintinib 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.
Since its launch in China, over 100,000 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
approved in the US, Europe and Japan. 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;
Pediatric population: There is no relevant use of FRUZAQLA in the pediatric
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 fetal harm. Animal studies have shown reproductive toxicity,
including fetal 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
fetus; 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.

 

·  Hemorrhagic events: Hemorrhagic 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.

 

Hematologic 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 erythrodysesthesia syndrome (PPES): PPES is the most
frequently reported dermato-logical 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
                          erythrodysesthesia 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)        hemorrhage, gastrointestinal perforation, pancreatic enzymes increased, oral
                          pain, rash, and mucosal inflammation

 

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 Japan Prescribing Information:

https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/400256_42910H0M1028_1_01
(https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/400256_42910H0M1028_1_01)

 

For EU Prescribing Information:

https://www.ema.europa.eu/en/documents/product-information/fruzaqla-epar-product-information_en.pdf
(https://www.ema.europa.eu/en/documents/product-information/fruzaqla-epar-product-information_en.pdf)

 

Forward‑Looking Statements

 

This press release 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 jurisdictions
such as Europe, 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, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED
undertakes no obligation to update or revise the information contained in this
press release, whether as a result of new information, future events or
circumstances or otherwise.

 

Medical Information

 

This press release 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.

 

 

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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