Unraveling innovation potential in the real-world setting: eighteen novel agents with twenty-six approved European indications, in the management of leukemias, lymphomas, and multiple myeloma

ABSTRACT

Introduction: Real-world effectiveness of hemato-oncology pharmaceuticals may not necessarily mimic clinical trial efficacy results, mainly due to demographic and clinical practice variability. The aim of this review was to systematically assess the availability of real-world evidence (RWE) and the transferability of clinical trial (CT) efficacy results to real life, for novel agents recently approved to manage lymphomas, leukemias, and multiple myeloma. This is the largest cross-indication review comparing RWE to CT results, aspiring to inform clinical practice and decision-making when funding hemato-oncology pharmaceuticals.

Areas covered: The review methodology focused on identifying all novel agents that entered EU landscape between 2012 and 2016 by using European Medicines Agency (EMA) database, while conducting a systematic PubMed literature review of RWE in the specific hematological malignancies, in order to compare RWE versus CT efficacy endpoints.

Expert opinion: In total, 18 international nonproprietary names (INNs) that received EMA approval for any indication were included and the registrational efficacy results are presented. Eight (44%) INNs proved to have relevant RWE generated in at least one approved indication. The analysis of findings revealed high variability in terms of RWE availability and transferability of CT results to relevant real-life experience among the disease areas investigated.

KEYWORDS:

• Hematological malignancies
• leukemia
• lymphoma
• myeloma
• real-world evidence

Article highlights

• Real-world evidence will be of increasing importance for both regulators and payers, as scarcity of resources will dictate coverage and prescribing prioritization based on the observed real-life value on top of regulatory success.

• Novel oncology therapies will continue to occupy significant share of the pharmaceutical spending and hence are a priority for decision makers across the globe.

• This review achieved to demonstrate the significant lack of RWE investments post regulatory registration for the 18 recently approved INN’s, as only 14 European studies were included across the 26 indications (EMA approval 2012–2016). An exception appears to be Brentuximab Vedotin in Relapse refractory Hodgkin Lymphoma, however this INN also benefited from longest time post-regulatory approval.

• For the eight INN’s with available RWE, there was significant variability in terms of the transferability of clinical trial efficacy results to real-life clinical practice. Specifically, when including both EU and non-EU RWE studies, multiple myeloma indication surfaced four RWE studies with one study demonstrating better results, one study worse results and two studies non-comparable results versus clinical trial setting. In leukemias, two RWE studies delivered worse results, six were aligned and one was not comparable versus clinical trial results. Finally, in lymphomas, 12 RWE studies proved alignment, three delivered worse outcomes, one study demonstrated better results and four studies were not comparable versus clinical trial results.

• No correlation between time post-regulatory approval and number of RWE publications could be identified. It seems that a minimum of 2 years is needed to publish RWE results post marketing authorization.

• Regulators and the pharmaceutical industry need to cater for registrational trial design and result transferability to clinical practice, potentially starting by including RWE commitments to conditional approvals.

Declaration of interest

I Petrakis was an employee of Takeda Pharmaceuticals International. Takeda and its subsidiaries were not part of or aware of this research effort or have they approved the contents. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary Material

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Additional information

Funding

This paper was not funded.