Early Economic Modeling of Mutant TNF (mutTNF) As a BBB-Permeabilizing Adjunct in Breast Cancer Brain Metastases: A UK NHS Perspective
Author(s)
Ankur Singh Chauhan, PhD1, Nicola R. Sibson, PhD2, Sandra Campbell, PhD2, Simon Lord, BM BCh, DPhil2, James Rose, BSc, PhD3, Mamta Bajre, MBBS3.
1Department of Strategic and Industry Partnerships, Health Innovation Oxford and Thames Valley, Oxford, United Kingdom, 2Department of Oncology, University of Oxford, Oxford, United Kingdom, 3Health Innovation Oxford and Thames Valley, Oxford, United Kingdom.
1Department of Strategic and Industry Partnerships, Health Innovation Oxford and Thames Valley, Oxford, United Kingdom, 2Department of Oncology, University of Oxford, Oxford, United Kingdom, 3Health Innovation Oxford and Thames Valley, Oxford, United Kingdom.
OBJECTIVES: Breast cancer brain metastases (BCBM) represent a significant clinical and economic burden, particularly in HER2-positive and triple-negative subtypes. The effectiveness of systemic therapies is limited by the blood-brain barrier (BBB), which restricts drug access to intracranial tumour sites. Mutant TNF (mutTNF), a TNFR1-selective biologic, is designed to transiently permeabilise the BBB at tumour-affected regions, enabling delivery of systemic therapies. This study presents an early-stage economic evaluation of mutTNF as an adjunct to standard NHS care for BCBM, and assesses its cost-effectiveness across treatment pathways, QALY scenarios, and pricing thresholds.
METHODS: A decision-analytic model was developed from the NHS perspective over a 1-year time horizon, comparing standard care with and without the addition of mutTNF. Standard care included systemic therapy alone or in combination with surgery or radiotherapy. Model inputs were derived from published literature, NICE technology appraisals, NHS reference costs, and relevant translational studies. The model estimated total costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and net monetary benefit (NMB). Analyses included a deterministic base-case, subgroup analysis by treatment modality, scenario analysis varying QALY gains (0.03-0.09), pricing threshold analysis, and probabilistic sensitivity analysis (PSA) with 100,000 Monte Carlo simulations.
RESULTS: Base-case analysis found mutTNF was dominant—more effective (+0.07 QALYs) and less costly (-£171.46), with an ICER of -£2,587 per QALY and an NMB increase of £2,160. Subgroup and Scenario analysis confirmed consistent cost-effectiveness across clinical pathways and QALY assumptions. mutTNF remained cost-effective up to £2,194 per dose. PSA showed cost-effectiveness in 90.3% of simulations at a £30,000/QALY threshold, with all simulations showing net health gain.
CONCLUSIONS: This early-stage evidence-based economic evaluation suggests that mutTNF can be a cost-effective adjunct to BCBM care, even under conservative assumptions. The findings offer strategic insights to inform value-based pricing, trial design, and early HTA engagement.
METHODS: A decision-analytic model was developed from the NHS perspective over a 1-year time horizon, comparing standard care with and without the addition of mutTNF. Standard care included systemic therapy alone or in combination with surgery or radiotherapy. Model inputs were derived from published literature, NICE technology appraisals, NHS reference costs, and relevant translational studies. The model estimated total costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and net monetary benefit (NMB). Analyses included a deterministic base-case, subgroup analysis by treatment modality, scenario analysis varying QALY gains (0.03-0.09), pricing threshold analysis, and probabilistic sensitivity analysis (PSA) with 100,000 Monte Carlo simulations.
RESULTS: Base-case analysis found mutTNF was dominant—more effective (+0.07 QALYs) and less costly (-£171.46), with an ICER of -£2,587 per QALY and an NMB increase of £2,160. Subgroup and Scenario analysis confirmed consistent cost-effectiveness across clinical pathways and QALY assumptions. mutTNF remained cost-effective up to £2,194 per dose. PSA showed cost-effectiveness in 90.3% of simulations at a £30,000/QALY threshold, with all simulations showing net health gain.
CONCLUSIONS: This early-stage evidence-based economic evaluation suggests that mutTNF can be a cost-effective adjunct to BCBM care, even under conservative assumptions. The findings offer strategic insights to inform value-based pricing, trial design, and early HTA engagement.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
EE347
Topic
Economic Evaluation, Health Technology Assessment, Medical Technologies
Topic Subcategory
Thresholds & Opportunity Cost
Disease
Biologics & Biosimilars, Neurological Disorders, Oncology, Personalized & Precision Medicine