Demonstration of Major Therapeutic Advantage From a Review of EU Conditional Marketing Authorizations in Oncology and Hematology.

In the EU, conditional marketing authorization is a pragmatic tool for early approval of a medicine that fulfills an unmet medical need. In the pharmaceutical legislation, an unmet medical need means that a condition lacks a satisfactory method for diagnosis, prevention, or treatment. If such satisfactory methods exist, the new medicinal product must hold a major therapeutic advantage for those affected, meaning that it must demonstrate an improvement in efficacy or safety over existing methods or, in exceptional cases, a major improvement in patient care. This review evaluates the approaches taken to justify a major therapeutic advantage in oncology and hematology products recommended for approval between 2006 and 2023. The review confirmed an increase in the number of conditional marketing authorizations over time. Out of a total of 65 CMAs, a satisfactory treatment method was available for 40 cases (61.5%), thereby requiring a demonstration of major therapeutic advantage to fulfill the unmet medical need requirement. Satisfactory treatments existed more often for the more recently approved medicinal products. Qualitative arguments and quantitative comparisons were common to demonstrate meaningful improvement in efficacy or safety. In the absence of head-to-head trials, indirect comparisons were often used. Most quantitative comparisons used naïve side-by-side comparisons, lacking adjustments for trial differences or quantification of uncertainty. Regulatory guidance on indirect comparisons and data requirements may be helpful to support applicants and assessors in making available promising medicines early that fulfill an unmet medical need and continue to meet rigorous efficacy and safety standards pending availability of comprehensive data post-approval.