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. 2018 Nov 28;13(1):214.
doi: 10.1186/s13023-018-0900-9.

Oncologic orphan drugs approved in the EU - do clinical trial data correspond with real-world effectiveness?

Yvonne Schuller  1 , Marieke Biegstraaten  2 , Carla E M Hollak  2 , Heinz-Josef Klümpen  3 , Christine C Gispen-de Wied  4 , Violeta Stoyanova-Beninska  4
Affiliations

Oncologic orphan drugs approved in the EU - do clinical trial data correspond with real-world effectiveness?

Yvonne Schuller et al. Orphanet J Rare Dis. .

Abstract

Background: Evaluation of evidence for efficacy of orphan medicinal products (OMPs) for rare malignancies may be hampered by the use of tumor measurements instead of clinical endpoints. This may cause efficacy data to not always match effectiveness in the real-world. We investigated whether an efficacy-effectiveness gap exists for oncologic OMPs and aimed to identify which factors contribute to it. Also, the magnitude of the clinical efficacy of oncologic OMPs was evaluated.

Methods: We included all oncologic OMPs authorized in the European Union from 2000 to 2017. Pivotal studies were evaluated by means of the European Society for Medical Oncology - Magnitude of Clinical Benefit Scale (ESMO-MCBS). To estimate real-world effectiveness, a literature search was performed to identify post-marketing studies, of which data on overall survival (OS) were extracted. OS of the new OMP was compared with OS data of standard of care. An OS gain of ≥3 months compared to pre-marketing data was considered clinically relevant.

Results: Twenty OMPs were included, of which 5 were authorized based on OS as a primary endpoint. 10 OMPs had post-marketing data available, of which 40% did not show a clinically relevant OS gain in the real world. All OMPs that were studied with OS as primary endpoint in the pivotal study had a clinically relevant OS gain in the real world. Furthermore, all OMPs that had a high ESMO-MCBS score and post-marketing data available, resulted in a clinically relevant OS gain in the real world.

Conclusions: Although the sample size is small, our results indicate an efficacy-effectiveness gap for oncologic OMPs exists. Significant changes in PFS do not always lead to an increased OS. The use of PFS may be justified, but validation of surrogate endpoints is needed.

Keywords: Effectiveness; Efficacy; Endpoints; Oncology; Orphan drugs.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

YS has no conflicts of interest. Over the past 3 years, MB has received travel support from Sanofi Genzyme once. MB and CH have not performed any paid consultancies nor received fees for speaking at conferences. The Academic Medical Center participates in clinical trials with Sanofi Genzyme and Protalix and received support for registries from Sanofi Genzyme and Shire HGT. None of the support or grants are related to the submitted work. Over the past 3 years, HJK received compensation for advisory board membership from IPSEN. His institution received research grant for a clinical trials from BAYER and Novartis.

This publication is a summary of the European Public Assessment Reports and the summary of product characteristics available on the EMA website, focusing on the main issues discussed during the scientific evaluation. Healthcare professionals and interested readers are referred to the EMA website for up-to-date information on this marketing authorization (http://www.ema.europa.eu). The authors remain solely responsible for the opinions expressed in this publication.

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