Abstract Background Belzutifan, a hypoxia-inducible factor 2 alpha inhibitor, was approved in the United States in August 2021 to treat VHL-associated renal cell carcinoma (RCC), central nervous system hemangioblastomas (CNS-Hb), and pancreatic neuroendocrine tumors (pNETs). Given belzutifan’s relatively recent market approval, real-world data on its clinical and healthcare resource utilization (HRU) outcomes remain limited. This study aimed to evaluate the impact of belzutifan on clinical procedures and HRU among patients with VHL treated with belzutifan. Methods This retrospective cohort study selected adult patients with evidence of a VHL diagnosis who initiated belzutifan on or after August 13, 2021, using administrative claims data from the Komodo Research Data (KRD+) database (January 1, 2016 to December 31, 2023). Evidence of VHL disease was identified using diagnosis codes, supplemented by a claims-based algorithm. The index date for each patient was defined as the date of their first belzutifan prescription in their claims history. Patient characteristics and comorbidity profile were summarized during the baseline period of 6 months before the index date, during which patients were continuously covered by healthcare insurance. Incidence rate ratios (IRRs) for tumor reduction procedures (TRPs), HRU, VHL monitoring procedures, and analgesic use were estimated using generalized linear mixed models with random effects to compare the monthly incidence rates during the 2-year pre- and post-index periods surrounding belzutifan initiation. All models were adjusted for age, sex, geographic region and insurance plan. Results The analysis included 140 VHL patients treated with belzutifan, with a mean (standard deviation SD) age of 41.1 (14.2) years at the index date, and an equal distribution of males and females. Most patients were white (52.1%) and enrolled in commercial insurance plans (81.4%). Compared to the pre-index period, the monthly incidence rate of any TRP was significantly reduced by 60% (IRR 95% CI =0.4 0.3, 0.6, P .01) over the 2 years following belzutifan initiation (Figure 1a). Most notably, surgical removal of cerebellar and spinal hemangioblastomas and retinal laser therapy was significantly reduced by 70% (0.3 0.1, 0.9, P .05) and 50% (0.5 0.3, 1.0, P .05) respectively. During the post-index period, the use of ultrasound increased by 50% (1.5 1.0, 2.2, P .05), while no significant differences were found in other imaging or monitoring procedures (1.1 1.0, 1.2, P = .14), or analgesic use (1.1 1.0, 1.3, P = .11) (Figure 1 b). Additionally, all-cause inpatient (IP) admissions significantly declined by 40% (0.6 0.4, 0.9, P .05), while outpatient (OP) visits significantly increased by 50% (1.5 1.4, 1.5, P .01) (Figure 1c). Conclusions Belzutifan use was associated with significant reduction in TRP burden and fewer hospitalizations, alongside stable analgesic use, suggesting potential real-world clinical benefit in managing VHL disease. The increase in ultrasound utilization, along with a shift from IP to OP care, suggests a transition toward lower-intensity, surveillance-focused management following belzutifan initiation. These findings provide real-world evidence of belzutifan’s impact on clinical management in patients with VHL.
Lukas et al. (Wed,) studied this question.