IS A CURATIVE GENE THERAPY FOR MULTIPLE SCLEROSIS COMMERCIALLY VIABLE? A RISK-ADJUSTED NET PRESENT VALUE ANALYSIS
Author(s)
Attila Imre, PharmD1, Balázs Nagy, PhD2, Rok Hren, PhD3.
1Center for Health Technology Assessment, Semmelweis University, Budapest, Hungary, 2Semmelweis University, Budapest, Hungary, 3Syreon Research Institute, Budapest, Hungary.
1Center for Health Technology Assessment, Semmelweis University, Budapest, Hungary, 2Semmelweis University, Budapest, Hungary, 3Syreon Research Institute, Budapest, Hungary.
OBJECTIVES: Multiple sclerosis (MS) imposes substantial clinical and economic burden, yet current disease-modifying therapies require lifelong administration without restoring immune tolerance. IMMUTOL, a tolerogenic gene therapy under development within an EU-funded Horizon Europe programme, aims to induce durable remission via genetically enhanced vitamin D3-modified tolerogenic dendritic cells. This study assessed the early financial feasibility of IMMUTOL from a developer's perspective.
METHODS: A risk-adjusted net present value (rNPV) model was constructed in monthly cycles, incorporating development costs, phase-specific probabilities of clinical and regulatory success (cumulative likelihood of approval: 10.1%), manufacturing expenditure, post-launch operating costs, and revenue projections derived from a diffusion-based market share function. A 10% discount rate was applied. Uncertainty was examined through one-way sensitivity analysis (±10%), probabilistic sensitivity analysis (1,000 Monte Carlo iterations), and scenario analyses varying price, production cost, discount rate, time to approval, and eligible population.
RESULTS: Under base-case assumptions, IMMUTOL generated a deterministic rNPV of -$223.8 million with an internal rate of return (IRR) of 3.4%. Probabilistic analysis yielded a mean rNPV of -$99.4 million and mean IRR of 10.5%, with 72.9% of iterations producing negative values. Peak annual sales reached $217.5 million (4,730 patients). Treatment price was the most influential parameter (rNPV swing: $93.5 million), followed by cost to marketing authorization ($83.6 million) and production cost ($53.4 million). Only scenarios combining higher prices with lower manufacturing costs produced consistently positive rNPVs: at $1.5 million price and $200,000 production cost, rNPV reached $711.2 million (IRR 20.7%).
CONCLUSIONS: A structural gap exists between the value-based price for IMMUTOL (previously estimated ≤$500,000) and the price required for commercial viability (>$1 million). Without alternative payment models, public-private partnerships, or substantial reductions in manufacturing costs, commercial development of curative gene therapies for high-prevalence indications such as MS may be economically unattractive despite clinical promise.
METHODS: A risk-adjusted net present value (rNPV) model was constructed in monthly cycles, incorporating development costs, phase-specific probabilities of clinical and regulatory success (cumulative likelihood of approval: 10.1%), manufacturing expenditure, post-launch operating costs, and revenue projections derived from a diffusion-based market share function. A 10% discount rate was applied. Uncertainty was examined through one-way sensitivity analysis (±10%), probabilistic sensitivity analysis (1,000 Monte Carlo iterations), and scenario analyses varying price, production cost, discount rate, time to approval, and eligible population.
RESULTS: Under base-case assumptions, IMMUTOL generated a deterministic rNPV of -$223.8 million with an internal rate of return (IRR) of 3.4%. Probabilistic analysis yielded a mean rNPV of -$99.4 million and mean IRR of 10.5%, with 72.9% of iterations producing negative values. Peak annual sales reached $217.5 million (4,730 patients). Treatment price was the most influential parameter (rNPV swing: $93.5 million), followed by cost to marketing authorization ($83.6 million) and production cost ($53.4 million). Only scenarios combining higher prices with lower manufacturing costs produced consistently positive rNPVs: at $1.5 million price and $200,000 production cost, rNPV reached $711.2 million (IRR 20.7%).
CONCLUSIONS: A structural gap exists between the value-based price for IMMUTOL (previously estimated ≤$500,000) and the price required for commercial viability (>$1 million). Without alternative payment models, public-private partnerships, or substantial reductions in manufacturing costs, commercial development of curative gene therapies for high-prevalence indications such as MS may be economically unattractive despite clinical promise.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EE584
Topic
Economic Evaluation, Health Policy & Regulatory, Methodological & Statistical Research
Disease
Neurological Disorders, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)