Accelerated approval for primary biliary cholangitis in 2016 came with three postmarketing requirements, but studies were terminated early; firm working toward sNDA submission in 2023 for regular approval, but US FDA says reports already are overdue and it expects to take PBC indication back to an adcomm.

Although US FDA reaffirmed its support of surrogate endpoints described in a 2018 draft guidance on NASH fibrosis, advisory committee members questioned the link to clinical benefit and said obeticholic acid’s serious risks made it difficult to consider the effect on the surrogate in a vacuum.

Obeticholic acid clinical outcomes data from Phase III trial are needed before approval, US FDA advisory committee says, but Intercept suggests future of ongoing study is in doubt if accelerated approval in nonalcoholic steatohepatitis is not forthcoming now.

Given the challenges of validating patient-reported outcome instruments specific to very rare diseases, agency is probably going to have to accept the use of unvalidated measures in some cases, Peter Marks tells American Society of Gene and Cell Therapy’s annual meeting.

Ahead of advisory committee vote on accelerated approval, agency takes a dim view of obeticholic acid's benefit-risk balance for the treatment of liver fibrosis due to NASH, citing risks of drug-induced liver injury and morbidity associated with biopsies necessary for appropriate patient selection.

Sarepta conducted study-level and integrated-level comparison analyses of SRP-9001-treated patients and external controls. However, heterogeneous nature of DMD and potentially moderate treatment effect of SRP-9001 distinguish it from Novaritis' spinal muscular atrophy treatment, where natural history data were used to support single-arm trial results, the FDA said.