Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence from the IMCgp100-202 trial indicates that tebentafusp significantly improves overall survival compared to usual treatments, with a median overall survival of 21.7 months versus 16.0 months for the comparator arm. This demonstrates a clear clinical advantage, although the benefit on progression-free survival is less pronounced.
Cost effectiveness
The cost-effectiveness estimates for tebentafusp fall within the acceptable range for Healthcare resources, particularly when considering the end-of-life criteria. The committee concluded that tebentafusp is cost-effective, with an ICER that aligns with NICE’s thresholds.
Quality of life
While specific HRQoL data is not extensively detailed, the evidence suggests that tebentafusp is well tolerated and allows patients to maintain a relatively normal life during treatment. Patient experts indicated that quality of life is often improved compared to before starting treatment, supporting a moderate gain in HRQoL.
Supporting Domains
Safety and Adverse Effects
Tebentafusp has a manageable safety profile, with most adverse events occurring early in treatment and being tolerable. Although there are more adverse events compared to usual treatments, they are generally short-lived and do not significantly undermine the treatment’s overall value.
Comparator Selection
The IMCgp100-202 trial compared tebentafusp against an appropriate standard of care, primarily pembrolizumab, which is the most commonly used treatment for advanced uveal melanoma. This selection reflects current clinical practice and addresses the lack of standard care for this condition.
Patient Population and Subgroups
The trial population is generally representative of the intended patient population, focusing on HLA-A*02:01-positive patients. However, there are some limitations regarding age and the specific subgroup analysis, which could affect generalizability.
Care Pathway Integration
Tebentafusp can be integrated into existing care pathways with minor adjustments, such as the need for HLA-A*02:01 testing, which is feasible within current clinical practice. The committee noted that the treatment would not require significant infrastructure changes.
Resource Use and Cost Implications
The resource implications of tebentafusp are manageable, with the potential for cost savings due to its effectiveness. The committee acknowledged that while there are costs associated with the treatment, they are justifiable given the expected health outcomes.
Evidence Quality and Robustness
The evidence base is supported by a well-conducted Phase III trial (IMCgp100-202) with a robust design. However, there are some uncertainties regarding long-term survival estimates and the extrapolation methods used in the economic model.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties in the overall survival modelling and cost-effectiveness estimates, the context of unmet need and the innovative nature of tebentafusp mitigate some of these concerns. The committee recognized the importance of addressing these uncertainties in decision-making.
