OBJECTIVES : Advanced therapy medicinal products (ATMPs) bring the promise of transformative advances in the treatment of life-threatening diseases. Drug developers, payers, and academics are increasingly working on suggesting innovative funding models adapted to ATMPs that include outcome-based and non-outcome based managed entry agreements (MEAs). MEAs aim to share the risk of uncertainties of new drugs. This study aims at identifying the MEAs currently used for ATMPs in the big 5 European countries (EU5).

METHODS : A search was conducted on 05/06/2019 in European Medicines Agency (EMA) website to identify ATMPs approved in Europe. The EU5 health technology assessment bodies’ official websites, developers’ websites and grey literature were searched to identify the MEAs used for approved ATMPs.

RESULTS : In Italy, outcomes-based MEAs are widely used; Holoclar® and Strimvelis® are reimbursed with a payment by result agreement and Zalmoxis® has a flat cost per patient. Whereas in England, most ATMPs are approved with patient access schemes that mainly consist of confidential discounts. The 2 CAR-Ts Kymriah® and Yescarta® are funded through the cancer drugs fund that allows developers to collect further clinical evidence to mitigate uncertainties. In France, price-volume agreements are used for ATMPs as for other pharmaceuticals. MEAs were rarely used in Germany, the first agreement done for an ATMP was for Kymriah® between Novartis and GWQ, a group of German health insurers. This agreement consists of a payback if survival outcomes are not met.

CONCLUSIONS : European countries are increasingly using a variety of MEAs to tackle uncertainty arising from lack of long-term clinical evidence, cost-effectiveness, and real life effectiveness. In view of the important number of ATMPs expected to reach the market, the call for innovative funding models is becoming ever louder. There is an urgent need of developing an infrastructure to harmonize and foster the use of MEAs.