— basedFRESCO‑42 globallyIII Positive results from phase clinical studies approved to treat patients with treated metastatic colorectal cancer —

— FRUZAQLA (Fruquintinib) becomes the first innovative targeted therapy approved by the European Union for the treatment of metastatic colorectal cancer in more than a decade, regardless of the patient's biomarker status —

Hong Kong, Shanghai, and Florham Park, New Jersey, June 22, 2024/PRNewswire/ -- Hutchmed (China) Limited (“HUTCHMED” or “HUTCHMED”) (NASDAQ/London Stock Exchange: HCM; HKEx: 13) today announced that its partner Takeda (TSE: 4502/NYSE: TAK) has obtained approval from the European Commission (European Commission) for FRUZAQLA (fruquintinib, fruquintinib) for use as monotherapy Treat existing standard treatments including chemotherapy, anti-vascular endothelial growth factor (“VEGF”) treatment, and anti-epidermal growth factor receptor (EGFR) therapy, and metastasis of disease progression or intolerance after treatment with trifluridine-pirtiacil (trifluridine-pirtiacil) or regorafenib (regorafenib) Patients with colorectal cancer.

Barcelona, SpainVall d'HebronOncology Research Institute (VHIO) DirectorJosep TaberneroPhD“Fruquintinib became the first and only selective inhibitor for all three VEGFR subtypes approved in the EU to treat colorectal cancer, and this decision marks an important milestone in European oncology,” he said. In Europe, treated patients with metastatic colorectal cancer and their clinicians are in dire need of new treatment options. We are delighted to have taken an important step forward in prescribing this new, differentiated medicine to patients.”

President of Takeda's Global Antitumor DivisionTeresa Bitetti“We are delighted that FRUZAQLA has received approval from the European Commission, and we can now provide new treatment options for patients with treated metastatic colorectal cancer, regardless of their biomarker status. “Metastatic colorectal cancer patients in Europe have been waiting for new treatment options for a long time, and we are honored to be able to meet this need through our partnership with Hewang Pharmaceuticals.”

Dr. Su Weiguo, CEO and Chief Scientific Officer of Hutchison Pharmaceuticals“This is an important milestone for Hewang Pharmaceuticals,” he said. This is the first product of our R&D engine to be approved in Europe, and through collaboration with Takeda, we have achieved this goal in such a short period of time. Currently, this innovative anti-tumor drug is improving treatment prospects for this disease in the US and China, and we look forward to bringing its impact to patients in Europe.”

This approval was granted by the European Commission following positive comments from the Commission for Human Medicines (“CHMP”) in April 2024. The CHMP opinion was mainly based on the results of the FRESCO-2 International Multi-Center Phase III study, which also supported the submission of a listing license application (MAA). The marketing license application was confirmed and accepted by the European Medicines Agency (EMA) in June 2023. Data from the FRESCO-2 study were published in “The Lancet (The Lancet)” in June 2023.

About colorectal cancer

Colorectal cancer is cancer that begins in the colon or rectum. According to the International Agency for Research on Cancer (IARC) /World Health Organization (WHO), colorectal cancer is the third most common cancer worldwide, with an estimated 1.9 million new cases and more than 900,000 deaths in 2022. Colorectal cancer is the second most common cancer in Europe, with around 538,000 new cases and 248,000 deaths in 2022.^{[1], [2]} In the US, an estimated 153,000 new cases of colorectal cancer and 53,000 new deaths will occur in 2024.^[3] Colorectal cancer is the most common cancer in Japan, with an estimated 146,000 new cases and 60,000 deaths in 2022.^[2]Although early stage colorectal cancer can be removed through surgery, treatment results for metastatic colorectal cancer are currently poor and treatment options are limited, and there are still many unmet medical needs. Although some patients with metastatic colorectal cancer may benefit from individualized treatment strategies based on molecular characteristics, most patients do not carry mutations that can be targeted for treatment.^{[4], [5], [6], [7], [8]}

regardingFRESCO‑42 IIITerm research

The FRESCO‑2 study is an international multicenter clinical trial conducted in the US, Europe, Japan, and Australia to explore fruquintinib combined with optimal supportive treatment versus placebo combined with optimal supportive treatment for the treatment of patients with metastatic colorectal cancer (NCT04322539). The FRESCO‑2 study reached all major endpoints and key secondary endpoints, showed significant statistically and clinically significant improvements in overall survival (OS) and progression-free survival (PFS), and showed consistent benefits among patients treated with fruquintinib regardless of previous treatment. Fruquintinib showed controlled safety in the FRESCO-2 study, consistent with those reported in previously published clinical trials of fruquintinib monotherapy. Among patients receiving fruquintinib combined with optimal supportive treatment, 20% experienced adverse reactions leading to discontinuation of treatment, compared to 21% of patients receiving placebo combined with optimal supportive treatment. The results of the study were presented at the European Society of Medical Oncology (ESMO) annual meeting in September 2022, followed by “The Lancet (The Lancet)” in June 2023.^{[9], [10]} 

About Fruquintinib

Fruquintinib is an oral inhibitor that selectively targets all three VEGFR (VEGFR-1, -2, and -3). VEGFR inhibitors play a critical role in inhibiting tumor angiogenesis. Fruquintinib is designed to have higher kinase selectivity and is designed to reduce off-target kinase activity, thereby achieving higher drug exposure, continued target coverage, and greater flexibility when potentially used as a combination therapy. To date, fruquintinib has shown controlled safety characteristics, and research on its combined use with other anti-tumor treatments is ongoing.

About Takeda andFRUZAQLA

Takeda has exclusive global licenses to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong, and Macau. Fruquintinib was approved in the US in November 2023 and marketed by Takeda under the trade name FRUZAQLA. The US approval was based on data from two large-scale, randomized controlled phase III clinical trials, the international multi-center clinical trial FRESCO-2 study and the FRESCO study conducted in China, which showed consistent benefits among a total of 734 patients treated with fruquintinib. The safety characteristics of the studies were also consistent.

In addition to the application submitted to the EMA, an application was submitted to the Japan Pharmaceuticals and Medical Devices Administration (PMDA) in September 2023.

About fruquintinib approved in China

Fruquintinib has been approved for marketing in China, and sold under the trade name ELUNATE (ELUNATE) in cooperation with Hutchison Pharmaceuticals and Eli Lilly. It was included in China's national medical insurance drug catalogue in January 2020. The FRESCO study, a phase III critical registration study of fruquintinib in 416 patients with metastatic colorectal cancer in China, supported the approval of fruquintinib in China. The results of the study were published in the “Journal of the American Medical Association (JAMA)”. Since fruquintinib was marketed in China, more than 80,000 colorectal cancer patients have been treated with fruquintinib as of mid-2023.

About Hwasong Pharmaceutical

Hutchison Pharmaceuticals (NASDAQ/LSE: HCM; HKEx: 13) is an innovative, commercialized biomedical company dedicated to the discovery, global development and commercialization of targeted drugs and immunotherapy treatments for cancer and immune diseases. The Group's companies have a total of about 5,000 employees, of which the core oncology/immunization business has a team of about 1,800 people. Since its establishment, Hewang Pharmaceutical has been committed to bringing self-discovered anti-tumor drug candidates to patients around the world. The first three drugs have now been marketed in China, and the first of these drugs has also been marketed in the US. For more details, visit ‑med.com or follow our LinkedIn page.

Important safety information in Europe 

Please refer to the FRUZAQLA (fruquintinib) Product Characteristics Summary (SmPC) before prescribing.

User guide:FRUZAQLA should be used first by physicians with experience in anti-tumor treatment. Packaging instructions should be provided to patients.

Contraindications:Hypersensitivity to the active ingredient or any of the excipients.

Special groups: Renal insufficiency:Patients with mild, moderate or severe renal insufficiency do not need dose adjustment;Hepatic insufficiency:Patients with mild or moderate hepatic insufficiency do not need dose adjustments. FRUZAQLA is not recommended for patients with severe hepatic insufficiency because there are no FRUZAQLA studies on this population;Elderly people:Patients over the age of 65 do not need to adjust the dose;Group of children:FRUZAQLA has no relevant usage data for metastatic colorectal cancer indications in children;Women of childbearing age/Female contraception:Women of childbearing age should be advised to use effective contraception during treatment and for at least 2 weeks after the last dose of FRUZAQLA;pregnancy:There are no clinical data on FRUZAQLA for pregnant women. Depending on its mechanism of action, FRUZAQLA may cause harm to the fetus. Animal studies have shown reproductive toxicity, including fetal malformations. FRUZAQLA should not be used during pregnancy unless the woman's clinical situation requires FRUZAQLA treatment. If FRUZAQLA is used during pregnancy or if the patient becomes pregnant during treatment, the patient must be informed of the potential harm to the fetus;Breastfeeding:It has not been determined whether FRUZAQLA is safe to use while breastfeeding. It is currently unclear whether FRUZAQLA or its metabolites are excreted through human milk. There are no animal data on FRUZAQLA excretion through animal milk. The risks faced by breastfed newborns/infants cannot be ruled out. Stop breastfeeding during treatment and within 2 weeks after the last dose;Fertility:There is no data on FRUZAQLA's impact on human fertility. Animal studies have shown that FRUZAQLA may impair male and female fertility.

Warnings and Precautions

• High blood pressure: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 medicated with antihypertensive drugs and the dose of FRUZAQLA adjusted if necessary. FRUZAQLA should be permanently discontinued for patients with high blood pressure or hypertensive crisis that cannot be controlled by antihypertensive therapy.
• Bleeding events:Bleeding events, including gastrointestinal bleeding, have been reported in patients treated with FRUZAQLA. Serious or even life-threatening bleeding events have been reported in patients treated with FRUZAQLA.
  Patients at risk of bleeding (including those receiving anticoagulants or other concomitant medications that increase the risk of bleeding) should be monitored for hematological and coagulation characteristics in accordance with standard medical practices. FRUZAQLA should be permanently discontinued in the event of severe bleeding requiring immediate medical intervention.
• Gastrointestinal perforation:Gastrointestinal perforations, including fatal events, have been reported in patients treated with FRUZAQLA.
  Symptoms of gastrointestinal perforation should be monitored regularly during FRUZAQLA treatment.
  Patients with gastrointestinal perforations should permanently discontinue FRUZAQLA.
• proteinuria: Proteinuria has been reported in patients treated with FRUZAQLA.
  Proteinuria should be monitored according to standard medical practices before starting FRUZAQLA and throughout treatment. If the urine test strip detects proteinuria greater than 2 g in 24 hours, it may be necessary to interrupt the dose, adjust the dose, or discontinue the drug. Patients with nephrotic syndrome should permanently discontinue FRUZAQLA.
• palmoplantar erythematous sensation syndrome (PPES):Palmoplantar erythematous sensation syndrome is the most commonly reported adverse skin reaction.
  If skin reactions above grade 2 are detected, dose interruption, dose adjustment, or discontinuation may be necessary.
• reversible posterior encephalopathy syndrome (PRES): In clinical studies, a case (0.1%) of patients treated with FRUZAQLA was reported to have reversible posterior encephalopathy syndrome. It is a rare neurological disorder that can present with or without high blood pressure, headache, seizures, drowsiness, confusion or altered mental function, blindness, and other visual or neurological disorders. Reversible posterior encephalopathy syndrome requires brain imaging, preferably magnetic resonance imaging (MRI). For patients with reversible posterior encephalopathy syndrome, it is recommended that FRUZAQLA be discontinued and given supportive medical management to control high blood pressure and other symptoms.
• Delayed wound healing: In clinical studies, one case (0.1%) of patients treated with FRUZAQLA was reported to have delayed wound healing.
  Patients are advised not to take FRUZAQLA for at least 2 weeks prior to major surgery. Do not use FRUZAQLA for at least 2 weeks after major surgery until there is evidence that the wound has fully healed according to clinical indications.
• Arterial and venous thromboembolic events: Patients with a history of thromboembolic events (including deep vein thrombosis and pulmonary embolism) or a history of stroke and/or transient ischemic attack within the past 6 months are advised to avoid starting FRUZAQLA treatment. FRUZAQLA should be discontinued immediately in patients suspected of having arterial thromboembolism.

Drug Interactions

Other drug pairs FRUZAQLA Pharmacokinetic effects of

CYP3Ainducer

Co-administer FRUZAQLA with rifampicin (a potent CYP3A inducer) 600 mg once daily to AUC FRUZAQLA_inf65% reduction, C_Max Decreased by 12%. Co-administration of FRUZAQLA with strong and moderate CYP3A inducers should be avoided.

CYP3Ainhibitors

FRUZAQLA was administered in combination with itraconazole (a potent CYP3A inhibitor) at 200 mg twice daily without regard to the area under the plasma drug concentration-time curve (AUC) and C_MaxIt has a clinically significant impact. There is no need to adjust the dose of FRUZAQLA when co-administered with CYP3A inhibitors.

acid-suppressing drugs

FRUZAQLA was co-administered with rabeprazole (a proton pump inhibitor) 40 mg once daily, and there was no clinically significant effect on the AUC of FRUZAQLA. There is no need to adjust the dose of FRUZAQLA when co-administered with antacid drugs.

FRUZAQLA Pharmacokinetic effects on other drugs

as P-glycoproteins (P-gp) Substrates for pharmaceutical products

The combination of a single dose of 150 mg dabigatran (a p-GP receptor) and a single dose of 5 mg FRUZAQLA reduced the AUC of dabigatran by 9%. There is no need to adjust the dose of the p-gp substrate when co-administered with FRUZAQLA inhibitors.

As a breast drug resistant protein (BCRP) Substrates for pharmaceutical products

Co-administration of a single 10 mg dose of rosuvastatin (a BCRP substrate) with a single 5 mg dose of FRUZAQLA reduced the AUC of rosuvastatin by 19%. There is no need to adjust the dose of the BCRP substrate when co-administered with FRUZAQLA inhibitors.

Adverse Reactions: FRUZAQLA Most common adverse reactionsYes:

Forward-looking statements

This announcement contains1995US Private Securities Litigation Reform Act“safe harbor“Forward-looking statements as defined in these terms. These forward-looking statements reflect Chi-Med's current expectations for future events, including expectations of the therapeutic potential of fruquintinib for colorectal cancer patients, and further clinical research plans for fruquintinib for this and other indications. Forward-looking statements involve risk and uncertainty. Such risks and uncertainties include the following assumptions: data sufficiency to support marketing licensing applications for fruquintinib approval in other regions (e.g., Japan) for colorectal cancer or other indications; the safety of furoquintinib; the safety of furoquintinib; the ability of Chu Huang to fund and implement and complete further clinical development plans and commercialization of furoquintinib; the timing of such events; the ability of each party to meet the terms and conditions of the licensing agreement; the actions of regulators may influence the initiation, timing and progress of clinical trials and the registration path of furoquintinib Ability to develop, produce and commercialize fruquintinib, etc. Furthermore, since some studies relied on the use of other pharmaceutical products in combination with fruquintinib, such risks and uncertainties include assumptions about the safety, efficacy, availability, and ongoing regulatory approval of these treatments. Current and potential investors should not unduly rely on these forward-looking statements, which are only valid as of the date of this announcement. For further discussion of these and other risks, please consult Hutchison Pharmaceuticals to the U.S. Securities and Exchange Commission,AIMand documents submitted by The Stock Exchange of Hong Kong Limited. Regardless of the emergence of new information, future events or circumstances, or other factors, Huhuang Pharmaceutical is not obligated to update or amend the information contained in this notice.

medical information

The products mentioned in this notice may not be marketed in all countries, or may be sold under different trademarks, or used for different conditions, or in different dosages, or have different effects. No information contained in this article should be construed as an application, promotion, or advertisement for any prescription drug, including those under development.

INSIDER INFORMATION

This announcement contains (EU) section596/2014Regulation No. 1 (This regulation forms “”2018Part of the EU reservation law as defined by the European Union (Withdrawal) Act) Section7Inside information as stipulated in section.