Fruquintinib has received positive opinion from the European Medicines Agency (EMA) CHMP for colorectal cancer

Chi-Med announces that Takeda has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) in support of fruquintinib for the treatment of treatment-treated metastatic colorectal cancer

— If approved in the EU, fruquintinib will be the first innovative targeted therapy approved for the treatment of metastatic colorectal cancer in more than a decade, regardless of a patient's biomarker status —

— Positive opinion based on the results of the FRESCO-2 Phase III clinical study —

HONG KONG, SHANGHAI AND FLORHAM PARK, N.J., April 26, 2024 /PRNewswire/ --

HUTCHMED (China) Limited

HUTCHMED (Nasdaq/AIM: HCM, HKEX: 13) today announced that its partner Takeda has received recommended approval from the European Medicines Agency's ("EMA") Committee for Medicinal Products for Human Use ("CHMP") for fruquintinib for the treatment of adult patients with treatment-treated metastatic colorectal cancer.

The European Commission (EC) will take into account the positive CHMP input when deciding on the marketing authorization of fruquintinib for the treatment of metastatic colorectal cancer throughout the European Union, 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 the treatment of previously treated metastatic colorectal cancer. [1],[2] Takeda has an exclusive worldwide license to further develop, commercialize and manufacture fruquintinib outside of Chinese mainland, Hong Kong and Macau.

Chief Medical Officer, Oncology, Takeda Awny Farajallah Doctor of Medicine

"Through our collaboration with Chi-Med, we have made great strides in expanding the accessibility of fruquintinib to applicable patients. With the positive CHMP for fruquintinib, we are one step closer to providing patients in the EU with an oral and non-chemotherapeutic option that promises significant survival benefits. We look forward to a formal decision from the European Commission in the near future. "

Dr. Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED

"Chi-Med has a proven track record of developing innovative oncology medicines for patients in need. Currently, there are limited treatment options available to patients with metastatic colorectal cancer in the EU, resulting in poor treatment outcomes. "We are pleased that our partner Takeda is making progress in redefining the treatment landscape and addressing the significant unmet needs of patients with metastatic colorectal cancer in Europe." Over the past five years, this innovative oncology drug has had a profound impact on patients in China. Since our partnership with Takeda, we have seen the scope of this impact further expanded, with approval and marketing in the U.S. and now awaiting approval by the European Commission, and we expect the drug to have a positive impact on patients in Europe as well." "

The positive opinion of the CHMP is based on the results of the FRESCO-2 international multicenter Phase III study, which also supported the submission of the Marketing Authorization Application (MAA). The MA was confirmed and accepted by the EMA 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), colorectal cancer is the third most common cancer worldwide. It was estimated to have killed more than 935,000 people in 2020. In Europe, colorectal cancer is the second most common cancer, with about 520,000 new cases and 245,000 deaths in 2020. [3] In the United States, an estimated 153,000 new cases of colorectal cancer and 53,000 deaths will occur in 2024. [4] Colorectal cancer is the most common cancer in Japan, with an estimated 148,000 new cases and 60,000 deaths in 2020. [3] Although early-stage colorectal cancer can be surgically removed, there is still a significant unmet medical need for metastatic colorectal cancer with poor treatment outcomes and limited treatment options. While some patients with metastatic colorectal cancer may benefit from personalized treatment strategies based on molecular signatures, the majority do not harbor mutations that could be targeted for treatment. [5],[6],[7],[8],[9]

concerning FRESH ‑ 2 III

Phase of the study

The FRESCO-2 study is an international, multi-center clinical trial conducted in the U.S., Europe, Japan and Australia to investigate fruquintinib plus best supportive care versus placebo plus best supportive care in patients with previously treated metastatic colorectal cancer (NCT04322539). The FRESCO-2 study met all primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS), as well as consistent benefit in patients receiving fruquintinib, regardless of prior therapy. Fruquintinib demonstrated a manageable safety profile in the FRESCO-2 study, consistent with those reported in previously published fruquintinib clinical trials. Adverse reactions leading to treatment discontinuation occurred in 20% of patients receiving fruquintinib in combination with best supportive care, compared with 21% of patients receiving placebo plus best supportive care. The results of the study were presented at the European Society for Medical Oncology (ESMO) Congress in September 2022 and subsequently presented in The Lancet in June 2023. [10],[11]

About FruquintinibFruquintinib is a selective oral VEGFR-1, -2 and -3 inhibitor. VEGFR inhibitors play a crucial role in inhibiting angiogenesis in tumors. Fruquintinib is designed to have higher kinase selectivity and is designed to reduce off-target kinase activity, resulting in higher drug exposure, sustained target coverage, and greater flexibility when potentially used as combination therapy. To date, fruquintinib has demonstrated a manageable safety profile and is being studied in combination with other anti-tumor therapies.

About Takeda Kazu

FRUZAQLA®

Takeda has an exclusive global license to further develop, commercialize and manufacture fruquintinib outside of Chinese mainland, Hong Kong and Macau. Fruquintinib was approved in the U.S. in November 2023 and is marketed by Takeda under the brand name FRUZAQLA®. The U.S. approval was based on data from two large, randomized controlled Phase III clinical trials, the international multicenter trial of FRESCO-2 and the FRESCO study in China, which demonstrated consistent benefit in a total of 734 patients treated with fruquintinib. The safety profile was also consistent across studies.

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

Fruquintinib was approved in China

Fruquintinib has been approved for marketing in China and is marketed by HUTCHMED and Eli Lilly under the brand name Elunate ®. It was included in the National Reimbursement Drug List of China in January 2020. The approval of fruquintinib in China was supported by a FRESCO study, a Phase III pivotal registration study of fruquintinib in 416 patients with metastatic colorectal cancer in China, whose results were published in the Journal of the American Medical Association (JAMA). As of mid-2023, more than 80,000 colorectal cancer patients have been treated with fruquintinib since its launch in China.

About HUTCHMED HUTCHMED (Nasdaq/AIM: HCM, HKEX: 13) is an innovative, commercial-stage biopharmaceutical company focused on discovering, developing and commercializing targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. The Group's companies employ approximately 5,000 people, including a team of approximately 1,800 in the core Oncology/Immunology business. Since its inception, Chi-Med has been committed to bringing its in-house discovery of oncology drug candidates to patients around the world, with the first three drugs now available in China, including the first in the United States. For more information, please visit: or follow us on LinkedIn.

Important U.S. Safety Information

Warnings and precautions

• Of the 911 patients with metastatic colorectal cancer treated with FRUZAQLA, 49% developed hypertension, of which 19% had grade 3-4 events, and 3 patients (0.3%) developed hypertensive crisis. DO NOT START FRUZAQLA UNLESS YOUR BLOOD PRESSURE IS WELL CONTROLLED. Blood pressure is monitored weekly for the first month and at least monthly thereafter as clinically indicated. Antihypertensive therapy is initiated or titrated as appropriate. Depending on the severity of hypertension, FRUZAQLA is suspended, dose reduced, or permanently discontinued.
• Bleeding events may occur during FRUZAQLA treatment and include severe, fatal events. Of the 911 patients with metastatic colorectal cancer treated with FRUZAQLA, 6% experienced gastrointestinal bleeding, of which 1% had a grade 3 event ≥ and 2 had fatal bleeding. For patients with severe or life-threatening bleeding, permanently discontinue FRUZAQLA. Patients receiving anticoagulant drugs should have their international normalized ratio (INR) levels monitored.
• Infect. FRUZAQLA may increase the risk of infection, including fatal infections. Among the 911 patients with metastatic colorectal cancer treated with FRUZAQLA, the most common infections were urinary tract infections (6.8%), upper respiratory tract infections (3.2%), and pneumonia (2.5%), while fatal infections included pneumonia (0.4%), sepsis (0.2%), bacterial infections (0.1%), lower respiratory tract infections (0.1%), and septic shock (0.1%). In the event of a grade 3 or 4 infection or worsening of any grade of infection, FRUZAQLA needs to be suspended. Once the infection is under control, the original dose of FRUZAQLA is resumed.
• Gastrointestinal perforation may occur in patients treated with FRUZAQLA. Of the 911 patients with metastatic colorectal cancer treated with FRUZAQLA, 1.3% experienced ≥ grade 3 gastrointestinal perforation, including one fatal event. Patients with raw gastrointestinal perforation or fistulas should be permanently discontinued with FRUZAQLA.
• Hepatotoxicity. FRUZAQLA can cause liver damage. Of the 911 patients with metastatic colorectal cancer treated with FRUZAQLA, 48% had elevated alanine aminotransferase ("ALT") or aspartate aminotransferase ("AST"), with 5% experiencing ≥ grade 3 events and 0.2% experiencing fatal events. Liver function (ALT, AST and bilirubin) should be monitored regularly before starting FRUZAQLA and throughout treatment. FRUZAQLA should be suspended, tapered, or permanently discontinued, depending on the severity and persistence of hepatotoxicity as evidenced by elevated liver function tests.
• Proteinuria. FRUZAQLA may cause proteinuria. Of the 911 patients with metastatic colorectal cancer treated with FRUZAQLA, 36% developed proteinuria and 2.5% experienced ≥grade 3 events. Proteinuria should be monitored regularly before starting FRUZAQLA and throughout treatment. If the 24-hour proteinuria is ≥ 2 g, FRUZAQLA should be withheld until improvement has reached grade ≤1 proteinuria and the dose should be lowered to continue FRUZAQLA therapy. Patients presenting with nephrotic syndrome should discontinue FRUZAQLA.
• Of the 911 patients treated with FRUZAQLA, 35% experienced a sensation of palmoplantar redness and swelling ("PPE"), of which 8% experienced a grade 3 event. Depending on the severity of the PPE, FRUZAQLA is suspended and then resumed at the original or reduced dose.
• Posterior reversible encephalopathy syndrome ("PRES"), which occurred in one of 911 patients treated with FRUZAQLA, is a subcortical angioedema syndrome diagnosed by characteristic findings on MRI. Any patient presenting with epilepsy, headache, visual disturbance, confusion, or altered mental function should be evaluated for PRES. FRUZAQLA should be discontinued in patients presenting with PRES.
• Delayed wound healing. Of the 911 patients with metastatic colorectal cancer treated with FRUZAQLA, one patient had a grade 2 wound dehiscence event. Do not take FRUZAQLA for at least 2 weeks before major surgery. Do not use FRUZAQLA for at least 2 weeks after major surgery until the wound has healed adequately. The safety of resuming FRUZAQLA treatment after resolution of wound healing complications has not been established.
• Arterial thromboembolic events. Of the 911 patients with metastatic colorectal cancer treated with FRUZAQLA, 0.8% had an arterial thromboembolic event. FRUZAQLA should be used with caution in patients with a recent thromboembolic event. In patients with arterial thromboembolism, FRUZAQLA should be discontinued.
• Allergic reaction to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF). FRUZAQLA 1mg capsules contain FD&C Yellow No. 5 (tartrazine), which may cause anaphylactic-type reactions (including bronchial asthma) in certain susceptible populations. FRUZAQLA 1mg contains FD&C Yellow No. 6 (Sunset Yellow FCF), which may cause allergic reactions.
• Embryonic – fetal toxicity. According to the results of animal studies and its mechanism of action, pregnant women taking FRUZAQLA may cause harm to the fetus. Pregnant women should be informed of the potential risks to the fetus. It is recommended that women of childbearing potential and men with female partners of childbearing potential use effective contraception during FRUZAQLA treatment and for 2 weeks after the last dose.

Adverse reactionsThe most common (incidence ≥20%) adverse reactions after FRUZAQLA treatment included hypertension, palmoplantar redness and swelling (hand-foot skin reactions), proteinuria, dysphonia, abdominal pain, diarrhoea, and fatigue.

Drug interactions: avoid concomitant administration of FRUZAQLA with strong or moderate CYP3A inducers.

Use in specific populations

• Breastfeeding: Women are advised not to breastfeed during FRUZAQLA treatment and for 2 weeks after the last dose.

To report a suspected adverse reaction, contact Takeda Pharmaceuticals at 1-844-662-8532 or contact FDA at 1-800-FDA-1088 or visit.

See full prescribing information for FRUZAQLA (fruquintinib).

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 Chi-Med's current expectations regarding future events, including its expectations as to whether and when the EMA will approve the marketing authorization application for fruquintinib for the treatment of colorectal cancer, its expectations regarding the therapeutic potential of fruquintinib for the treatment of patients with colorectal cancer, 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 adequacy of data supporting a marketing authorization application for fruquintinib in the EU or elsewhere (e.g., Japan) for the treatment of colorectal cancer or other indications, the potential for regulatory approval, the safety profile of fruquintinib, Chi-Med's ability to fund, realize and complete further clinical development plans and commercialization of fruquintinib, the timing of such events, the parties' ability to meet the terms and conditions of the license agreement, regulatory actions that may affect the initiation, timing and progression of clinical trials and the registration pathway for fruquintinib, and Takeda's ability to successfully develop, manufacture and commercialize fruquintinib. In addition, as some studies rely on the combination of fruquintinib with other drug products, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Current and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this announcement. For further discussion of these and other risks, please refer to HUTCHMED's filings with the U.S. Securities and Exchange Commission, AIM and The Stock Exchange of Hong Kong Limited. Chi-Med 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

The products mentioned in this announcement may not be available in all countries, or may be marketed under different trademarks, or used for different conditions, or at different dosages, or have different potencies. None of the information contained herein should be construed as an application, promotion, or advertisement for any prescription drugs, including those under development.

Inside information

This announcement contains inside information under Article 7 of Regulation (EU) No 596/2014 which forms part of EU reserved law as defined in the European Union (Withdrawal) Act 2018.

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