Adaptive pathways report clears way for continuation of EMA's early-access programme

The European Medicines Agency (EMA) published a final report on 3 August examining the "adaptive pathways" pilot project for early market-authorisation of medicines; the report (available here) marks the end of the EMA's pilot project. The programme is set to be scaled-up and continued, although the scheme is still regarded as being at a concept stage rather than a fully integrated procedure.

The adaptive pathways pilot was developed by the EMA in March 2014 to assess the potential of a staggered drug-approval process for medicines that treat high or unmet medical need in Europe. The initiative allowed for the approval of investigational drugs that are in early-stage development (Phase I/II) for use in a restricted patient population. This approval was conditional upon the collection of a wide range of evidence (from clinical trials and real-world evidence) in order that the market authorisation can be adapted and expanded to broader patient populations. The report seeks to examine how successful the adaptive pathways programme has been in fulfilling its main objective of accelerating patient access to new medicines that are not yet available on the market.

The types of medicines that have benefitted from the adaptive pathways pilot lay in rare-disease therapeutic areas, where difficulties exist in collecting sufficient clinical data. EMA officials have previously emphasised that the adaptive pathways programme can be a useful mechanism to enable "smaller, faster clinical trials that are likely to yield results earlier" (see Europe: 17 June 2016: EMA calls on adaptive-pathways stakeholders to commit to regulations for post-licensing "knowledge generation" collection plans). An EMA policy paper released during the first quarter of 2016 also noted significant untapped potential to expand the generation of real-world evidence, and raised the issue of "linking high technology and hospital drugs with real-world patient outcome data" (see Europe: 22 May 2016: European Commission publishes STAMP update on safe and timely access to medicines). Elsewhere, the non-governmental European Public Health Alliance (EPHA) also recently published a report, albeit more critical, on the impact that adaptive licensing has had on medicine affordability. In particular, the EPHA objected to what it described as a lack of transparency and "political scrutiny" of the drug prices concerned (see Europe: 23 May 2016: EPHA addresses issue of medicine affordability under new fast-track approval systems).

During the course of the project, the EMA received a total of 62 applications for inclusion in the pilot. Eighteen of these drug candidates were selected for in-depth consideration; of these, six applications progressed by receiving parallel advice from the EMA and health technology assessment (HTA) bodies. In addition, one application was chosen to receive formal scientific advice. The products submitted to parallel regulatory-HTA advice can be broken down into the following therapeutic areas: oncology (two products), haematology (two products), anti-infective (one product), and cardiovascular (one product).

Oncology medicines comprised about one-third of the applications received, and one-quarter of applicants had received an orphan drug designation from the European Commission at the time of submission.

While the vast majority of application cases were not considered appropriate for the pilot programme, the six applications that were forwarded for parallel advice met the EMA's original participation target.

The reasons provided for non-inclusion in the pilot were numerous; however, the EMA expressed particular concern that the majority of applications were "vague" on plans to collect real-world data to supplement randomised clinical trials or to confirm efficacy post-authorisation. Most applicants were not in a position to outline their real-world-data collection strategies.

To address this shortcoming, the regulator acknowledged that further work was required to refine and clarify use of "methodologically-sound strategies" for collecting real-world evidence on efficacy. A workshop with stakeholders and pharmaceutical companies, planned for 8 December, has been organised to examine this aspect in more detail. This marks a first step, but will eventually entail the necessity of reaching an agreement between pharmaceutical companies, stakeholders, and regulators on standards for the collection and use of real-world evidence.

Outlook and implications

The completed pilot project will be utilised to develop a more structured and sustainable framework going forward. The EMA has said that preparatory work on future adaptive pathways discussions will be published annually; pharmaceutical companies have also been invited to submit proposals to the EMA for participation in adaptive pathways schemes. Applications will be considered on the basis of updated guidance documents (available here).

Elsewhere, the agency has recommended that in future there should be greater involvement of patient groups in selecting adaptive pathway products. The pharmaceutical industry stands to benefit from this development, since the integration of patient groups would likely support accelerated access for certain medicines, particularly in the oncology area. Furthermore, the EMA report calls for increased participation by national-level payors in the process. Payors were not party to discussions under the pilot programme; their future participation would be beneficial, as this should allow pharmaceutical companies to link data collection with adaptive pricing strategies.