OBJECTIVES : Novel cell and gene therapies offer potentially curative benefits; however, due to orphan populations, lack of comparators, and immature long-term data, substantial uncertainty exists regarding clinical benefits. Moreover, cell and gene therapy are expensive with one-time price tags frequently exceeding $100,000. We sought to elucidate the quality of evidence reviewed by HTA organizations and their reimbursement decisions.

METHODS : Reimbursement recommendations from HTA agencies CADTH, NICE, SMC and AGDH (PBAC and MSAC) were reviewed for cell and gene therapies (2016-2019), and key clinical and economic data were extracted from submissions.

RESULTS : Less than 1% of all submissions were for cell and gene therapies, indicating that this treatment class is relatively small compared to others such as drugs and biosimilars. Tisagenlecleucel (for two indications) and axicabtagene ciloleucel were reviewed based on four distinct studies, all of which were phase 2, single-arm trials and received positive recommendations in all HTAs except AGDH. Other cell and gene therapies included nusinersen, patisiran, voretigene neparvovec, darvadstrocel, and inotersen, which were supported by phase 3 RCTs, and the majority received positive recommendations in all HTAs except AGDH. Incremental QALYs were as high as 11.1, demonstrating substantial clinical benefits. With CADTH, manufacturer base-case ICERs ranged from $53,629-$24,387,422/QALY, with NICE ranged from £16,704-£421,303/QALY, with SMC ranged from £25,238-£78,088/QALY, and with AGDH were either not reported or described as >$200,000/QALY. For CADTH, which reported the high ICERs, price reductions of up to 98% were found necessary for treatments to fall under the $50,000/QALY threshold.

CONCLUSIONS : HTA agencies accepted lower level data (phase 2 trials) and generally high ICERs exceeding regular thresholds for cell and gene therapies offering potentially substantial long-term benefits in patients with limited options. Transparency regarding risk-sharing agreements and price reductions would help manufacturers assess economic viability and potentially spur greater investment in cell and gene therapies.