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The Food and Drug Administration approved belzutifan (Welireg) for adult patients with von Hippel–Lindau disease (VHL) who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) that do not require immediate surgery.

Belzutifan is a selective small-molecule inhibitor of hypoxia-inducible factor and a first-in-class drug.

The new approval is based on safety and efficacy results from the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC with at least one measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNETs.

Patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity.

The overall response rate, which was the study’s primary endpoint, was 49% in patients with VHL-associated RCC. Additional efficacy endpoints included duration of response (DoR), which was not reached. So far, 56% of responders had DoR of at least 12 months. The median time to response was 8 months.

Among the patients in the study with other VHL-associated non-RCC tumors, 24 patients with CNS hemangioblastomas had an ORR of 63%, and 12 patients with pNETs had an ORR of 83%. Median DoR was not reached,with 73% and 50% of patients having response durations of at least 12 months for CNS hemangioblastomas and pNET, respectively.

The most common adverse reactions (≥20% of patients), according to the FDA, were decreased hemoglobin, anemia, fatigue, increased creatinineheadache, dizziness, increased glucose, and nausea.

Notably, anemia and hypoxia from belzutifan use can be severe. In Study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. Patients should be transfused as clinically indicated. Erythropoiesis-stimulating agents for anemia are not recommended in patients treated with belzutifan. In Study 004, hypoxia occurred in 1.6% of patients.

Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm; see full prescribing information for Welireg.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, and used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. The application was granted priority review by the FDA.

A version of this article first appeared on Medscape.com.

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The Food and Drug Administration approved belzutifan (Welireg) for adult patients with von Hippel–Lindau disease (VHL) who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) that do not require immediate surgery.

Belzutifan is a selective small-molecule inhibitor of hypoxia-inducible factor and a first-in-class drug.

The new approval is based on safety and efficacy results from the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC with at least one measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNETs.

Patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity.

The overall response rate, which was the study’s primary endpoint, was 49% in patients with VHL-associated RCC. Additional efficacy endpoints included duration of response (DoR), which was not reached. So far, 56% of responders had DoR of at least 12 months. The median time to response was 8 months.

Among the patients in the study with other VHL-associated non-RCC tumors, 24 patients with CNS hemangioblastomas had an ORR of 63%, and 12 patients with pNETs had an ORR of 83%. Median DoR was not reached,with 73% and 50% of patients having response durations of at least 12 months for CNS hemangioblastomas and pNET, respectively.

The most common adverse reactions (≥20% of patients), according to the FDA, were decreased hemoglobin, anemia, fatigue, increased creatinineheadache, dizziness, increased glucose, and nausea.

Notably, anemia and hypoxia from belzutifan use can be severe. In Study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. Patients should be transfused as clinically indicated. Erythropoiesis-stimulating agents for anemia are not recommended in patients treated with belzutifan. In Study 004, hypoxia occurred in 1.6% of patients.

Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm; see full prescribing information for Welireg.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, and used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. The application was granted priority review by the FDA.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved belzutifan (Welireg) for adult patients with von Hippel–Lindau disease (VHL) who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) that do not require immediate surgery.

Belzutifan is a selective small-molecule inhibitor of hypoxia-inducible factor and a first-in-class drug.

The new approval is based on safety and efficacy results from the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC with at least one measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNETs.

Patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity.

The overall response rate, which was the study’s primary endpoint, was 49% in patients with VHL-associated RCC. Additional efficacy endpoints included duration of response (DoR), which was not reached. So far, 56% of responders had DoR of at least 12 months. The median time to response was 8 months.

Among the patients in the study with other VHL-associated non-RCC tumors, 24 patients with CNS hemangioblastomas had an ORR of 63%, and 12 patients with pNETs had an ORR of 83%. Median DoR was not reached,with 73% and 50% of patients having response durations of at least 12 months for CNS hemangioblastomas and pNET, respectively.

The most common adverse reactions (≥20% of patients), according to the FDA, were decreased hemoglobin, anemia, fatigue, increased creatinineheadache, dizziness, increased glucose, and nausea.

Notably, anemia and hypoxia from belzutifan use can be severe. In Study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. Patients should be transfused as clinically indicated. Erythropoiesis-stimulating agents for anemia are not recommended in patients treated with belzutifan. In Study 004, hypoxia occurred in 1.6% of patients.

Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm; see full prescribing information for Welireg.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, and used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. The application was granted priority review by the FDA.

A version of this article first appeared on Medscape.com.

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