WELIREG is the first HIF-2? inhibitor therapy approved in the
The WELIREG label contains a boxed warning that exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective. WELIREG can cause severe anemia that can require a blood transfusion. Monitor for anemia before initiation of WELIREG and periodically throughout treatment. WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Monitor oxygen saturation before initiation of and periodically throughout treatment with WELIREG. For more information, see 'Selected Safety Information' below.
'VHL disease is a rare and serious condition. Until today, there were no systemic therapies approved to help treat patients diagnosed with certain types of VHL-associated tumors,' said Dr.
'WELIREG is the first and only approved systemic therapy for patients with certain types of VHL-associated tumors, representing an important new treatment option for patients affected by this rare condition,' said Dr.
'The approval of a non-surgical treatment option is meaningful for helping patients with certain types of VHL-associated tumors,' said Dr.
Data Supporting the Approval
The approval was based on data from Study 004 ( ClinicalTrials.gov, NCT03401788), an open-label trial in 61 patients with VHL-associated RCC diagnosed based on a VHL germline alteration and with at least one measurable solid tumor (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNET. CNS hemangioblastomas and pNET in these patients were diagnosed based on the presence of at least one measurable solid tumor in the brain/spine or pancreas, respectively, as defined by RECIST v1.1 and identified by an independent review committee (IRC). The study excluded patients with metastatic disease. Patients received WELIREG at a dose of 120 mg once daily until progression of disease or unacceptable toxicity. In Study 004, the median duration of exposure to WELIREG was 68 weeks (range, 8.4 to 104.7).
The study population characteristics were: median age of 41 years (range, 19 to 66), 3.3% age 65 or older; 53% male; 90% white, 3.3% Black or
The major efficacy endpoint for the treatment of VHL-associated RCC was ORR measured by radiology assessment using RECIST v1.1 as assessed by IRC. Additional efficacy endpoints included duration of response (DoR) and time to response (TTR).
In patients with VHL-associated RCC (n=61), WELIREG showed an ORR of 49% (95% CI, 36-62); all responses were partial responses. Median DoR had not yet been reached (range, 2.8+ to 22.3+ months); among responders, 56% (n=17/30) were still responding after at least 12 months. Median TTR was eight months (range, 2.7 to 19).
In patients with VHL-associated CNS hemangioblastomas (n=24), WELIREG showed an ORR of 63% (95% CI, 41-81), with a complete response rate of 4% (n=1) and a partial response rate of 58% (n=14). Median DoR had not yet been reached (range, 3.7+ to 22.3+ months); among responders, 73% (n=11/15) were still responding after at least 12 months. Median TTR was three months (range, 3 to 11).
In patients with VHL-associated pNET (n=12), WELIREG showed an ORR of 83% (95% CI, 52-98), with a complete response rate of 17% (n=2) and a partial response rate of 67% (n=8). Median DoR had not yet been reached (range, 10.8+ to 19.4+ months); among responders, 50% (n=5/10) were still responding after at least 12 months. Median TTR was eight months (range, 3 to 11).
Serious adverse reactions occurred in 15% of patients who received WELIREG, including anemia, hypoxia, anaphylaxis reaction, retinal detachment and central retinal vein occlusion (1 patient each). Permanent discontinuation of WELIREG due to adverse reactions occurred in 3.3% of patients. Adverse reactions that resulted in permanent discontinuation of WELIREG were dizziness and opioid overdose (1.6% each).
Dosage interruptions of WELIREG due to an adverse reaction occurred in 39% of patients. Adverse reactions that required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache and influenza-like illness. Dose reductions of WELIREG due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction that required dose reduction was fatigue (7%).
The most common adverse reactions (?25%), including laboratory abnormalities, that occurred in patients treated with WELIREG were decreased hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%) and nausea (31%).
About Von Hippel-Lindau Disease
The incidence of
WELIREG (belzutifan) Indication in the
WELIREG (belzutifan) is indicated for the treatment of adult patients with
Selected Safety Information
Warning: Embryo-Fetal Toxicity
Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective.
Anemia
WELIREG can cause severe anemia that can require blood transfusion. In Study 004, anemia occurred in 90% of patients and 7% had Grade 3 anemia. In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, anemia occurred in 76% of patients and 28% had Grade 3 anemia.
Monitor for anemia before initiation of and periodically throughout treatment. Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers due to potential increases in exposure that may increase the incidence or severity of anemia.
Transfuse patients as clinically indicated. For patients with hemoglobin
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