This analysis explores the unique regulatory and market access challenges that ATMP developers face and provides guidance on avoiding recognized pitfalls through a fully integrated approach, with reference to recent approvals in lymphoma, retinal and Crohn’s disease. ATMPs are evolving quickly due to the fact that they treat life-threatening diseases with high unmet need, and because of enabling technologies which directly impact on development. These include targeted modification of many different cell types, significant advances in gene delivery capabilities, including a variety of vectors and emerging genome editing technologies (e.g. CRISP-R), innovative regulatory elements (e.g. synthetic promoters) and inducible elements to regulate gene expression (e.g. molecular kill switches to improve safety). There are 850+ regenerative medicine companies and almost 1,000 clinical trials worldwide (314 Ph1, 550 Ph2, 82 Ph3). However there are still only 10 products with marketing authorization in Europe (4 subsequently withdrawn) and 8 in the U.S. ATMPs have yet to be successfully commercialized. Many things contribute to this:

• Long-term safety remains a potential issue and experience is insufficient
• Maintenance of efficacy after single administration a challenge to ensure and measure with significant impact on risk/benefit assessment
• Many products target orphan indications with small patient populations, sparse data at launch
• Use of surrogate or new outcomes measures and novel trial designs, leading to lack of familiarity/preparedness in payer communities
• Challenge to meet payers’ survival and comparative data requirements
• Treatment costs and patient benefits are not matched over time
• Uncertainty over duration of effect makes ATMPs difficult to value/price
• Current healthcare system and payment models not designed with ATMPs in mind. Institution-level decision vs individual physicians with no mechanisms to drive timely implementation of nationally scalable solutions
• Many pilot value and performance–based annuity models fail, partly due to lack of information systems to reliably collect and evaluate outcomes