What is FRUZAQLA^®(fruquintinib)?

FRUZAQLA is a non-chemotherapy kinase inhibitor

Treatments are needed in metastatic colorectal cancer (mCRC) to improve outcomes and preserve quality of life. FRUZAQLA may be able to help. FRUZAQLA is a kinase inhibitor of vascular endothelial growth factor receptors (VEGFRs) for adult patients with previously treated mCRC, regardless of mutation status.^1-4

•    Approved in 2023 based on the FRESCO and FRESCO-2 clinical trials⁴
•    Convenient, once-daily oral dosing⁴
•    An innovation in mCRC treatment⁴

Treatments that extend survival while preserving QoL are needed to reduce mortality rates in metastatic colorectal cancer (mCRC)^1-3

Colorectal cancer (CRC) can be deadly, with low survival rates for patients with metastatic disease³

of patients with CRC will experience metastatic disease, whether at diagnosis or over the course of treatment¹

5-year relative survival rate for patients with distant mCRC³

Treatment of CRC can be intense and can negatively impact QoL

The symptomology of CRC and cytotoxic agent treatment-related side effects can substantially impact patients’ well-being⁵

Fatigue, insomnia, and/or psychological challenges can all affect emotional, social, physical, and functional status⁵
Management of adverse events, to maintain quality of life, is a key consideration with current options for previously treated metastatic colorectal cancer⁶

Therapies that consider the delicate balance of efficacy, tolerability, and quality of life are desperately needed^1-3

**National Comprehensive Cancer Network^® (NCCN^®) recommends Fruquintinib (FRUZAQLA^®) as a potential NCCN Category 2A* treatment option for patients with previously treated mCRC^7,8,†**

FRUZAQLA is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine , oxaliplatin , and irinotecan based chemotherapy, an anti VEGF therapy, and, if RAS wild type and medically appropriate, an anti-EGFR therapy.⁴

Potential treatment algorithms^†‡

FRUZAQLA Mechanism of Action

FRUZAQLA is a novel, selective inhibitor of all 3 VEGF receptors with limited off-target kinase activity, allowing for high drug exposure and sustained target inhibition^4,9,10¶¶

FRUZAQLA is a small molecule kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3^4,9,10

FRUZAQLA® (fruquintinib) selectivity against a panel of 253 kinases.

AGC=protein kinase A, G, and C families; CAMK=calcium/calmodulin-dependent protein kinases; CK1=casein kinase 1; CMGC=cyclin-dependent kinase, mitogen-activated protein kinase, glycogen synthase kinase, and cyclin-dependent-like kinase; IC=inhibitory concentration; nM=nanometer; STE=serine/threonine‑specific protein kinase; TK=tyrosine kinase; TKL=tyrosine kinase‑like kinase; µM=micrometer; VEGF=vascular endothelial growth factor; VEGFR=vascular endothelial growth factor receptor.

FRUZAQLA is a VEGFR inhibitor that specifically targets and blocks all 3 vascular endothelial growth factor receptors (VEGFR)^4,9,10

By inhibiting VEGFR-1 and VEGFR-2, FRUZAQLA restricts tumor growth and progression^10,13
By also inhibiting VEGFR-3, FRUZAQLA has the potential to inhibit lymphangiogenesis^10,14

^¶¶Preclinical activity does not necessarily correlate with clinical outcomes.

Quality of Life Data

Learn more about how Quality of Life was measured in FRESCO-2.

Discover QoL data

FRESCO-2 Efficacy Results

Learn about the efficacy results from FRESCO-2, a global, double-blind, placebo-controlled study with a heterogenous patient population.

Explore trial data

FRESCO-2 Safety Profile

Explore the safety profile of FRUZAQLA from the FRESCO-2 clinical trial.

Find safety data

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.

What is FRUZAQLA^®(fruquintinib)?

FRUZAQLA is a non-chemotherapy kinase inhibitor

Treatments that extend survival while preserving QoL are needed to reduce mortality rates in metastatic colorectal cancer (mCRC)^1-3

Colorectal cancer (CRC) can be deadly, with low survival rates for patients with metastatic disease³

Treatment of CRC can be intense and can negatively impact QoL