OBJECTIVES: To summarize the cost-effectiveness results from recent ICER advanced therapies medical products (ATMPs) reviews and analyze factors that contribute to the sensitivity of cost-effectiveness measures for the base case, health care system perspective.

METHODS: Recent ICER evidence reports (final/draft) for ATMPs – RPE65-mediated retinal disease (Luxturna), B-cell acute lymphoblastic leukemia (B-ALL) (Kymriah), B-cell lymphoma (Yescarta), and Spinal Muscular Atrophy (onasemnogene abeparvovec [AVXS-101]) – were reviewed to compile the base case, health care system perspective cost-effectiveness ratios for intervention (drugs) vs comparator and identify key factors affecting cost-effectiveness using one-way sensitivity analyses. In the absence of head-to-head clinical data for direct comparisons between treatments, comparators were Clofarabine (Kymriah), chemotherapies (Yescarta), standard-of-care (SoC, Luxturna), and best-supportive care (BSC, AVXS-101).

RESULTS: The incremental cost-effectiveness ratios (ICERs) for four disease areas ranged from $643,813/quality-adjusted life-year (QALY, Luxturna vs SoC) to $45,871/QALY (Kymriah vs Clofarabine). Kymriah (B-ALL) and Yescarta (B-cell lymphoma), assessed under normal value framework, were cost-effective at $50,000/QALY and $150,000/QALY thresholds, respectively. Luxturna and AVXS-101 were assessed under ultra-rare disorder framework ($500,000/QALY threshold); only AVXS-101 was cost-effective ($243,000/QALY). The incremental QALYs gained ranged from 11.77 years (AVXS-101 vs BSC) to 1.3 years (Luxturna vs SoC) while the incremental/blindness-free LYs gained ranged from 15.77 years (AVXS-101 vs BSC) to 4.1 years (Yescarta vs chemotherapy). One-way sensitivity analyses identified health state costs, utility, discount rate, and clinical measures as key factors affecting ICERs, ranked among top three in 42%, 33%, 17%, and 8%, respectively, of 4 intervention-comparator evaluations. Utilities and costs directly influence ICERs, and due to long-term benefits of some therapies, discount rates also play a role.

CONCLUSIONS: Understanding the detailed ICER evidence reviews for ATMPs will be useful for clinical development and commercialization of innovative therapies and help plan evidence generation from early development onwards to positively influence future cost-effectiveness reviews.