Takeda Receives Approval from European Commission for FRUZAQLA in Previously Treated Metastatic Colorectal Cancer
Takeda has received European Commission (EC) approval for FRUZAQLA (fruquintinib) as a treatment for adult patients with metastatic colorectal cancer (mCRC) who have exhausted other standard therapies. This approval follows the Phase 3 FRESCO-2 trial, which demonstrated significant efficacy and a manageable safety profile for FRUZAQLA. The EC decision was preceded by a positive opinion from the CHMP on April 25, 2024, and an FDA approval on November 8, 2023. FRUZAQLA is now the first new targeted therapy for mCRC in the EU in over a decade, providing a new option for patients regardless of their biomarker status.
- European Commission approval of FRUZAQLA for mCRC treatment.
- Based on successful Phase 3 FRESCO-2 trial results showing efficacy.
- Manageable safety profile with adverse reaction rates similar to placebo.
- First novel targeted therapy for mCRC in the EU in over a decade.
- approval scope to patients who have exhausted other standard therapies.
- Adverse reactions led to treatment discontinuation in 20% of patients.
The approval of FRUZAQLA (fruquintinib) by the European Commission for previously treated metastatic colorectal cancer (mCRC) marks a significant advancement in the oncology landscape. For years, treatment options for mCRC have been limited, especially for those who have exhausted conventional therapies. FRUZAQLA is unique as it is chemotherapy-free and targets cancer cells in a more specific manner, increasing the precision of treatment. This approval is based on the robust Phase 3 FRESCO-2 trial, which demonstrated a significant benefit in terms of overall survival and progression-free survival. It's noteworthy that the drug performed consistently well, regardless of the prior therapy regimens, which underscores its potential to become a critical component of mCRC treatment. This could improve patient outcomes significantly and provide a new beacon of hope for those battling this aggressive cancer.
From a financial perspective, the European approval of FRUZAQLA is a strategic win for Takeda. The European market represents a substantial opportunity and the approval of a novel cancer therapy can potentially lead to a significant increase in revenue streams. Considering the high prevalence of metastatic colorectal cancer and the demand for new treatments, this drug is likely to see strong uptake. Moreover, the drug's approval despite its novel mechanism adds a competitive edge for Takeda in the oncology space. Investors should watch for Takeda's upcoming earnings reports as increased sales from FRUZAQLA could positively impact revenue. However, it's essential to note the potential for pricing pressures and market competition from other pharmaceutical companies launching similar therapies.
The approval of FRUZAQLA signifies a major shift in the approach to treating mCRC. The fact that FRUZAQLA works irrespective of biomarker status is particularly remarkable, setting it apart from many other targeted therapies that are limited by specific genetic mutations. This broad applicability can be game-changing in clinical settings, offering a new line of treatment where previously there might have been none. The manageable safety profile reported in the FRESCO-2 trial is also a key highlight, indicating that patients can stay on treatment longer without severe adverse effects. Clinical adoption will likely be swift given these compelling trial results, but continuous post-market surveillance will be important to monitor long-term efficacy and safety.
− Approval Based on Results from Positive, Global, Phase 3 FRESCO-2 Trial
− FRUZAQLA (fruquintinib) is the First Novel Targeted Therapy in the EU for Metastatic Colorectal Cancer (mCRC) Regardless of Biomarker Status in Over a Decade
“People living with metastatic colorectal cancer face numerous difficulties, stemming both from their illness and the adverse effects of therapies. Given the complex nature of the disease, introducing innovative treatments such as fruquintinib – an oral, chemotherapy-free targeted agent – is essential. I am looking forward to having a new choice for appropriate patients,” said Josep Tabernero, MD, PhD, director of Vall d´Hebron Institute of Oncology (VHIO).
The approval is based on results from the Phase 3 multi-regional FRESCO-2 trial. The trial investigated FRUZAQLA plus best supportive care (BSC) versus placebo plus BSC in patients with previously treated mCRC. FRESCO-2 met all its primary and key secondary efficacy endpoints and showed consistent benefit among patients treated with FRUZAQLA, regardless of the prior types of therapies they received. FRUZAQLA demonstrated a manageable safety profile in FRESCO-2. Adverse reactions leading to treatment discontinuation occurred in
“Today's approval marks an important moment for the colorectal cancer community in the EU. For the first time in over a decade, patients with previously treated metastatic colorectal cancer have a new targeted treatment option that can be used irrespective of whether their tumors harbor actionable mutations,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. “We look forward to offering patients a novel treatment option that has a manageable safety profile and can be effective regardless of the prior types of therapies they have received.”
About FRUZAQLA (fruquintinib)
FRUZAQLA is a selective oral inhibitor of all three VEGF receptors (-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 potential use as part of combination therapy.
Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland
EUROPEAN UNION 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; Paediatric population: There is no relevant use of FRUZAQLA in the paediatric 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 foetal harm. Animal studies have shown reproductive toxicity, including foetal 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 foetus; 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
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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.
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Haemorrhagic events: Haemorrhagic 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.
Haematologic 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.
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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.
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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.
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Palmar-plantar erythrodysaesthesia syndrome (PPES): PPES is the most frequently reported dermatological adverse reaction.
If Grade ≥ 2 skin reactions are detected, dose interruptions, adjustments, or discontinuation may be necessary.
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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.
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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 AUCinf by
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 Cmax 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
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
UNDESIRABLE EFFECTS: The most commonly reported adverse reactions with FRUZAQLA are:
Very common (frequency ≥1/10) |
Thrombocytopenia, hypothyroidism, anorexia, hypertension, dysphonia, diarrhoea, stomatitis, aspartate aminotransferase increased, total bilirubin increased, alanine aminotransferase increased, palmar-plantar erythrodysaesthesia syndrome, musculoskeletal discomfort, arthralgia, proteinuria, asthenia, and fatigue |
Common (≥1/100 to <1/10) |
Pneumonia, upper respiratory tract infection, bacterial infections, leukopenia, neutropenia, hypokalemia, epistaxis, throat pain, gastrointestinal haemorrhage, gastrointestinal perforation, pancreatic enzymes increased, oral pain, rash, and mucosal inflammation |
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 and was associated with more than 1.9 million new cases and 900,000 deaths in 2022. In
About the Phase 3 FRESCO-2 Trial
The FRESCO-2 study is a multi-regional clinical trial conducted in the
About Takeda
Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in
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