In Reply Chen and colleagues raise 2 important points in response to our analysis of beremagene geperpavec (B-VEC) therapy¹: the high costs of therapy may be offset by reductions in other health care costs, and cost-effectiveness analysis (CEA) would help assess the value of B-VEC therapy.

We agree with both points. B-VEC therapy will undoubtedly be associated with cost offsets, but these offsets are likely to differ substantially between those with autosomal recessive disease (RDEB)—associated with debilitating symptoms and limited life expectancy—and milder autosomal dominant forms of the disease (DDEB). The pivotal GEM-3² clinical trial included only a single patient with DDEB and, thus the benefits of B-VEC therapy in DDEB remain uncertain even though the costs of using B-VEC to treat the disease will be the same for both variants. Because the budgetary offsets for those with DDEB will likely be much lower than for those with RDEB and because DDEB itself is a heterogenous disease, careful attention must be paid to differential gains associated with treating RDEB and DDEB when analyzing the net financial burden of this extremely expensive therapy.