ReachMD

Transcript

Voiceover:
Von Hippel-Lindau, or VHL, disease is a rare, genetic, lifelong syndrome that can cause recurrent tumor development in several systems and organs.

Due to the chronic and unpredictable nature of VHL disease–associated tumors, patients often experience a cycle of watching and waiting, with few options…

But every patient’s journey with VHL disease is unique. That’s why a patient-centered focus is key to properly treating the manifestations of this lifelong condition.

Meet Wendy, a hypothetical, 27-year-old patient with VHL disease-associated RCC and CNS hemangioblastomas.

Wendy’s journey with VHL disease first began last year, when imaging from a back injury revealed two asymptomatic CNS hemangioblastomas: one in the cerebellum (measuring 1.0 cm) and another in the spinal cord (measuring 1.4 cm).

Wendy’s age, coupled with multiple tumors in the CNS, triggered speculation from her care team of a VHL disease diagnosis. Genetic testing confirmed that Wendy had VHL disease.

Additional imaging was ordered to look for other VHL-related tumors. This imaging revealed another CNS hemangioblastoma in the cerebellum (measuring 0.5 cm) and a solitary renal tumor (measuring 1.0 cm).

Because Wendy’s tumors remained asymptomatic, her care team recommended follow-up monitoring.

Since her diagnosis, Wendy does her best to manage life with VHL disease. As the first in her family with a VHL disease diagnosis, she has questions about living with a chronic condition…

After recent consultations with a neurosurgeon and urologist, they determine that Wendy does not need immediate surgery based on disease burden, tumor growth rate, distribution, and clinical course.

Wendy sees her oncologist, who prescribes WELIREG (belzutifan) to treat her VHL disease–associated CNS hemangioblastomas and RCC.

Voiceover:
WELIREG is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

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.

Selected Safety Information continues.

Voiceover:
WELIREG is the only approved systemic therapy for appropriate patients with certain VHL disease–associated tumors not requiring immediate surgery.

Voiceover:
Anemia

• WELIREG can cause severe anemia that can require blood transfusion.
  • Monitor for anemia before initiation of, and periodically throughout, treatment. Transfuse patients as clinically indicated. For patients with hemoglobin <8 g/dL, withhold WELIREG until ≥8 g/dL, then resume at the same or reduced dose or permanently discontinue WELIREG, depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥8 g/dL, then resume at a reduced dose or permanently discontinue WELIREG.

• In LITESPARK-004 (N=61), decreased hemoglobin occurred in 93% of patients with VHL disease and 7% had Grade 3 events. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months).
• The safety of erythropoiesis-stimulating agents (ESAs) for treatment of anemia in patients with VHL disease treated with WELIREG has not been established.

Hypoxia

• WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization.
• Monitor oxygen saturation before initiation of, and periodically throughout, treatment. For decreased oxygen saturation with exercise (eg, pulse oximeter <88% or PaO₂ ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (eg, pulse oximeter <88% or PaO₂ ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a health care provider.
• In LITESPARK-004, hypoxia occurred in 1.6% of patients.

Embryo-Fetal Toxicity

• Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman.
• Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Adverse Reactions

• In LITESPARK-004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).
• WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).
• Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.
• Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).
• The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin (93%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

Drug Interactions

• Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.
• Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

Lactation

• Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

Females and Males of Reproductive Potential

• WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.
• Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.
• Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown.

Pediatric Use

• Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established.

Before prescribing WELIREG, please read the accompanying Prescribing Information, including the Boxed Warning about embryo-fetal toxicity. The Medication Guide also is available.

Voiceover:
Visit welireghcp.com to learn more about the mechanism of action, efficacy (including response times), safety, and dosing of this systemic therapy.

References:

1. Larcher A, Belladelli F, Fallara G, et al. Multidisciplinary management of patients diagnosed with von Hippel-Lindau disease: a practical review of the literature for clinicians. Asian J Urol. 2022;9(4):430–442.
2. National Organization for Rare Disorders. Von Hippel-Lindau disease. http://rarediseases.org/rare-diseases/von-hippel-lindau-disease/. Accessed November 13, 2023.
3. Varshney N, Kebede AA, Owusu-Dapaah H, et al. A review of von Hippel-Lindau syndrome. J Kidney Cancer VHL. 2017;4(3):20–29.
4. Ganeshan D, Menias CO, Pickhardt PJ, et al. Tumors in von Hippel-Lindau syndrome: from head to toe—comprehensive state-of-the-art review. RadioGraphics. 2018;38(3):849–866.
5. Rare diseases at FDA. US Food and Drug Administration. https:/www.fda.gov/patients/rare-diseases-fda. Accessed February 6, 2024.
6. Narayan V, Jonasch E. Systemic therapy development in von Hippel-Lindau disease: an outsized contribution from an orphan disease. Cancers (Basel). 2022;14(21):5313.
7. Center for Drug Evaluation and Research. Advancing Health Through Innovation: New Drug Therapy Approvals 2021. https://www.fda.gov/media/155227/download. Published January 2022. Accessed February 6, 2024. 

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