Therapeutic benefit of orphan drugs in oncology: evidence at the point of European Marketing Authorisation

Odnoletkova I, Marjenberg Z, Pooley N, Langham S. Therapeutic benefit of orphan drugs in oncology: evidence at the point of European Marketing Authorisation. Value Health 2019;22(Suppl 3): S491

Abstract

Objectives: We analysed evidence on therapeutic benefit of orphan oncology medicines approved in the past five years, at the point of marketing authorisation by the European Medicine Agency (EMA).

Methods: Orphan oncology medicines authorised in 2014-2018 were identified from the EMA website. Data on trial design, overall survival (OS), progression free survival (PFS), adverse events (AEs) and health related quality of life (HRQoL) were extracted from the European Public Assessment Reports.

Results: In the last five years, 23 products were approved in 38 rare oncology indications, eight of which were granted conditional marketing authorisation (CMA). Evidence was based on single-arm studies in 67% and 31% of CMA and full approvals respectively, with the remainder based on final or interim results of randomised controlled trials (RCTs). Included were three potentially curative advanced therapies for rare blood cancers which showed a significant increase in complete response rates compared to historical controls. Of those medicines evaluated through RCTs, prolonged PFS (1.2 to 19.9 months) was demonstrated in 64%, prolonged OS (1.0 to 49.2 months) in 36%, and increased number of serious AEs in 77%. Data on HRQoL was available in 64% of RCTs, of which 18% demonstrated improvement. All drugs were subject to post-approval evidence generation or surveillance.

Conclusions: In rare oncology, particularly in potentially life-saving personalised treatments, demonstration of therapeutic benefit through RCTs is not always feasible, and nearly a half of approvals is based on single-arm studies. Most drugs evaluated in randomised settings demonstrated improvements in progression free survival, however there were frequent increases in serious adverse events. Evidence of overall survival gain was available in less than half of indications. Commitments to post-approval evidence generation were required for all medicines. Further efforts aimed at adaptive approaches to evidence generation are warranted, to ensure timely patient access and to stimulate innovation in medical practice.