VALUE DELAYED IS VALUE DENIED: COST-EFFECTIVENESS CHALLENGES FOR PRESYMPTOMATIC GENE THERAPIES
Author(s)
Lewis Hall, MEng, EngD, Richard Macaulay, BA, PhD.
Precision AQ, London, United Kingdom.
Precision AQ, London, United Kingdom.
OBJECTIVES: Gene therapies given presymptomatically may deliver benefit only years or decades after administration. This analysis used presymptomatic Huntington’s disease (HD) gene therapy as a case study to test how benefit-latency affects estimated cost-effectiveness under NICE methods, and whether existing flexibilities offset it.
METHODS: A cost-effectiveness threshold analysis compared a hypothetical therapy with best supportive care. The therapy gave a fixed annual QALY gain, starting only after a latency period and lasting a set durability. Inputs were anchored to published data: list price £1.65 to £2.88 million (spanning four recommended gene therapies) and annual QALY gain 0.3 to 0.8 (from HD utility data). Latency (5-20 years), discount rate (1.5%-3.5%), durability (10-30 years or lifetime), and NICE flexibilities (reduced 1.5% rate; severity weighting) were varied in sensitivity analyses. ICERs were compared with the current standard threshold (£25,000-£35,000/QALY) and the Highly Specialised Technologies (HST) threshold (£100,000-£300,000).
RESULTS: Across the pricing and QALY-gain assumptions, the reference-case ICER (3.5% discount) stayed above £100,000 at all 5 to 20 year latencies and never neared the £25,000 to £35,000 standard range (base £176,000 to £361,000). The 1.5% rate lowered the ICER by 37% (5 years) to 48% (20 years), independent of price and QALY gain. Both flexibilities together extended the £300,000-clearing latency from 17 to 38 years. The ICER was most sensitive to durability and assumed QALY gain.
CONCLUSIONS: HD’s UK prevalence (around 1 in 8,000) exceeds the HST ultra-rarity limit (1 in 50,000), so it would likely face standard appraisal rather than the higher HST threshold available to ultra-rare conditions. There the latency-inflated ICER is unreachable without a very deep confidential discount that latency enlarges. Presymptomatic long-latency therapies like HD fall in a structural gap; too common for HST and its benefits too delayed for standard cost-effectiveness.
METHODS: A cost-effectiveness threshold analysis compared a hypothetical therapy with best supportive care. The therapy gave a fixed annual QALY gain, starting only after a latency period and lasting a set durability. Inputs were anchored to published data: list price £1.65 to £2.88 million (spanning four recommended gene therapies) and annual QALY gain 0.3 to 0.8 (from HD utility data). Latency (5-20 years), discount rate (1.5%-3.5%), durability (10-30 years or lifetime), and NICE flexibilities (reduced 1.5% rate; severity weighting) were varied in sensitivity analyses. ICERs were compared with the current standard threshold (£25,000-£35,000/QALY) and the Highly Specialised Technologies (HST) threshold (£100,000-£300,000).
RESULTS: Across the pricing and QALY-gain assumptions, the reference-case ICER (3.5% discount) stayed above £100,000 at all 5 to 20 year latencies and never neared the £25,000 to £35,000 standard range (base £176,000 to £361,000). The 1.5% rate lowered the ICER by 37% (5 years) to 48% (20 years), independent of price and QALY gain. Both flexibilities together extended the £300,000-clearing latency from 17 to 38 years. The ICER was most sensitive to durability and assumed QALY gain.
CONCLUSIONS: HD’s UK prevalence (around 1 in 8,000) exceeds the HST ultra-rarity limit (1 in 50,000), so it would likely face standard appraisal rather than the higher HST threshold available to ultra-rare conditions. There the latency-inflated ICER is unreachable without a very deep confidential discount that latency enlarges. Presymptomatic long-latency therapies like HD fall in a structural gap; too common for HST and its benefits too delayed for standard cost-effectiveness.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA6
Topic
Economic Evaluation, Health Policy & Regulatory, Health Technology Assessment
Topic Subcategory
Value Frameworks & Dossier Format
Disease
Genetic, Regenerative & Curative Therapies