What payers will ask
Is the clinical benefit the kind payers reward? — Clinical effectiveness
The clinical effectiveness evidence for belzutifan is derived from a single-arm Phase 2 trial (MK-6482-004) which showed an objective response rate of 63.9% for RCC and 90.9% for pNETs. However, the evidence is limited by the lack of a comparator group and uncertainties regarding the clinical significance of the results, particularly in terms of symptom burden and the need for surgery. The committee noted that while belzutifan likely reduces tumor size, the overall clinical benefit remains uncertain.
Does the economic case hold at the expected price? — Cost effectiveness
The cost-effectiveness of belzutifan is uncertain due to significant structural uncertainties in the economic model. The committee noted that the ICERs were substantially greater than £30,000 per QALY gained, indicating low cost-effectiveness. Although belzutifan has potential for cost-effectiveness, more evidence is needed to clarify its economic value.
Is there quality-of-life evidence payers weigh? — Quality of life
No health-related quality of life data was collected in the MK-6482-004 trial. The committee noted that the utility values used in the economic model were derived from other studies and may not accurately reflect the population of interest. This absence of direct HRQoL data raises significant concerns about the treatment’s impact on patients’ overall well-being.
Does the safety profile hold up for payers? — Safety and Adverse Effects
Belzutifan has an acceptable safety profile, with adverse events primarily being mild to moderate. The committee noted that while there are some concerns regarding adverse effects, they are manageable and comparable to existing therapies. This suggests that the treatment is tolerable for patients.
Was the drug compared against what payers expect? — Comparator Selection
The comparator for belzutifan was standard care, primarily surgery, but the evidence from the MK-6482-004 trial was derived from a single-arm study. The committee highlighted that the lack of a direct comparator limits the robustness of the evidence and raises concerns about the validity of the comparisons made.
Is the population defined the way payers need it? — Patient Population and Subgroups
The trial population in MK-6482-004 included patients with VHL-associated RCC, CNS Hbs, and pNETs, but there were concerns about the representativeness of this population compared to the broader population eligible for treatment. The committee noted that the population may not fully align with the marketing authorization, which could limit generalizability.
Does the drug fit how care is delivered and paid for? — Care Pathway Integration
Belzutifan can be integrated into existing care pathways with minor adjustments. The committee noted that while some changes may be necessary, the treatment does not require extensive new infrastructure or training, making it relatively easy to adopt in clinical practice.
Are the wider system costs understood? — Resource Use and Cost Implications
The resource implications of belzutifan are notable, with the potential for high costs associated with its use. The committee expressed concerns about the budget impact, particularly given the uncertainties in the economic model and the potential need for innovative payment models to accommodate the treatment.
Would the evidence survive payer scrutiny? — Evidence Quality and Robustness
The evidence base for belzutifan is primarily derived from a single Phase 2 trial, which raises concerns about its robustness. The committee noted that while the trial was well-conducted, the lack of Phase 3 data and the uncertainties in the economic model limit the overall quality of the evidence.
How exposed is the case to uncertainty? — Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty surrounding the clinical and economic evidence for belzutifan. The committee acknowledged that while there are potential benefits, the uncertainties related to the treatment’s effectiveness and cost-effectiveness may restrict its use. The potential for managed access may help address some of these uncertainties.
