Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Regulatory acceptability of clinical surrogate endpoints for accelerated (US) or conditional (EU) approval of haematological anti-cancer drugs in the light of the new CHMP anti-cancer guideline (CHMP/205/95 Rev. 4 and appendices) and the new FDA draft guidance on expedited programs for serious conditions ***

Dr. Stephanie Sommer (Abschlußjahr: 2014)

Summary
One of the main goals of regulatory science is to support the development of novel drugs in a way that leads to a fast access of the drug to the market within the constantly evolving regulatory and scientific framework. Such a fast access is, in particular, in the interest of patients suffering from life-threatening diseases for which few or no treatment options are currently available. In order to ensure fast access of patients to drugs promising relevant improvements of their condition, both Food and Drug Administration (FDA) and European Medicines Agency (EMA) have devised pathways that are intended to speed up the drug approval process or to allow for the approval of drugs based on limited data sets.
In the European Union (EU), these pathways include conditional approval and approval under exceptional circumstances. To a certain extent the development and approval of drugs with orphan designation status may also be considered a pathway to fast approval, since the requirements on the extent of clinical trials conducted for an orphan drug are less extensive compared to those of a non-orphan drug. In the United States of America (US), accelerated approval, priority review and fast-track designation have been tools leading to fast drug developments and approvals for several years. Recently, FDA devised an additional regulatory path that may lead to fast approvals, namely breakthrough designation.
The precedence provided in this thesis suggests that response rates in one single-arm trial in populations with no (or very limited) treatment options may support accelerated or conditional approval, in some cases even full approvals, of compounds treating haematological malignancies. Although the type of approval granted, full or accelerated/conditional, varied in the US and the EU, in most cases similar data led to approvals in both legislations.
When aiming for an initial accelerated or conditional approval, sponsors should bear in mind that the initial approval will be most likely for a niche indication that may only generate limited revenue. In any case, comparative progression-free survival or overall survival data will need to be generated as a post-marketing commitment to achieve conversion to full approval, possibly in an earlier line of treatment. While post-marketing commitment are followed-up on, safety data may arise that could even further limit the approved indication.
With the availability of the new guidelines, the bar may be raised for certain indications, e.g. for chronic myelogenous leukaemia in the EU, however, they are expected to still provide a lot of room for discussion with the Agencies, especially in the context of the newly created breakthrough designation in the US. Early interaction with the authorities should be sought, both on the design of the trial leading to accelerated/conditional approval and on the design of the Phase III trial that would be expected as post-marketing commitment in case of an accelerated or conditional approval.
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