OBJECTIVES: In November 2017, the Food and Drugs Administration (FDA) announced a new regulatory framework for Regenerative Medicine Advanced Therapies (RMATs). In Europe, a similar regulatory framework has existed for Advanced Therapy Medicinal Products (ATMPs) since 2007. This research assesses the regulatory and commercial success of ATMPs and discusses their implications for RMATs in USA.

METHODS: European Commission (EC)-approved ATMPs were identified alongside their current FDA/EMA regulatory and reimbursement status in UK, Italy, and Germany from relevant regulatory/Health Technology Assessment (HTA) websites plus a targeted review of relevant company press releases (to 12/21/2017).

RESULTS: Nine ATMPs have received EC-approvals but only 3/9 were FDA-approved (one [Provenge^®] subsequently withdrawn). The first four EC-approved ATMPs (ChondroCelect^®, Glybera^®, MACI^®, Provenge^®) have all been withdrawn for commercial reasons after an average of 3.5 years on market (range: 1-7 years). Most notably, Glybera^®, the first EC-approved gene therapy (2012) priced at >€1 million/patient, was withdrawn in 2017 having reported only one commercial sale in 2016. Five others (Holoclar^®, Imlygic^®, Strimvelis^®, Zalmoxis^®, Spherox^®) have been EC-approved since 2015. There are limited HTA appraisals of these to date, only Strimvelis^® (the second EC-approved gene therapy) receiving >1 positive appraisal (AIFA and NICE). Nevertheless, only in March 2017, did Strimvelis^® receive its first commercial sale, despite being EC-approved since May 2016 with a 100% refund performance-based reimbursement scheme.

CONCLUSIONS: Only nine ATMPs have EC-approved in the decade since this regulatory framework was introduced but most of these approved therapies did not achieve FDA-approval. Nevertheless, the first four EC-approved ATMPs have been withdrawn from market for commercial reasons. Although in the US, regulatory approval typically forms the primary hurdle to patient access (unlike Europe where it is reimbursement) the FDA-withdrawal of Provenge^® for commercial reasons, emphasizes the magnitude of the commercial challenges facing such therapies in the US.