Cost-Effectiveness of Nadofaragene Firadenovec and Pembrolizumab in Bacillus Calmette-Guérin Immunotherapy Unresponsive Non–Muscle Invasive Bladder Cancer

Nadofaragene firadenovec is a gene therapy for bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) undergoing Food and Drug Administration review. Pembrolizumab is approved for treating patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS). We evaluated the cost-effectiveness of these treatments compared with a hypothetical therapeutic alternative, at a willingness-to-pay threshold of $150 000 per quality-adjusted life-year (QALY) gained, in CIS and non-CIS BCG-unresponsive NMIBC populations. We developed a Markov cohort simulation model with a 3-month cycle length and lifetime horizon to estimate the total costs, QALYs, and cost per additional QALY from the health sector perspective. Clinical inputs were informed by results of single-arm clinical trials evaluating the treatments, and systematic literature reviews were conducted to obtain other model inputs. Sensitivity analyses were conducted to assess uncertainty in model results. Nadofaragene firadenovec, at a placeholder price 10% higher than the price of pembrolizumab, had an incremental cost-effectiveness ratio of $263 000 and $145 000 per QALY gained in CIS and non-CIS populations, respectively. Pembrolizumab had an incremental cost-effectiveness ratio of $168 000 per QALY gained for CIS. A 5.4% reduction in pembrolizumab’s price would make it cost-effective. The model was sensitive to many inputs, especially to the probabilities of disease progression, initial treatment response and durability, and drug price. The cost-effectiveness of nadofaragene firadenovec will depend upon its price. Pembrolizumab, although not cost-effective in our base-case analysis, is an important alternative in this population with an unmet medical need. Comparative trials of these treatments are warranted to better estimate cost-effectiveness. •There are few therapeutic alternatives for the treatment of bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer. Although cystectomy is potentially curative, many patients are ineligible for or unwilling to undergo cystectomy. Nadofaragene firadenovec and pembrolizumab are new bladder-sparing treatments.•This study evaluated the lifetime cost-effectiveness of nadofaragene firadenovec and pembrolizumab from the US health sector perspective.•Using a placeholder price, nadofaragene firadenovec was cost-effective in the non–carcinoma in situ (CIS) population but not in the CIS population. Pembrolizumab, at its cu