October 20, 2014
Orphan drugs to treat rare and often life threatening diseases are authorized based on results from clinical trials in invariably limited patient numbers and accelerated approval procedures. Furthermore, the FDA recommends no population number thresholds for clinical trial safety studies for orphan drugs. In an article published in Expert Opinion on Orphan Drugs, O’Connell and Pariser compare and assess pre-market safety evaluation processes for rare and common disease drugs.
The authors indicate that patient numbers in common disease drug safety trials are nine times greater than numbers included in orphan drug studies. In efforts to mitigate the higher risk uncertainty associated with orphan drug use, the FDA requires orphan drug developers to satisfy Risk Evaluation and Mitigation Strategy (REMS) programs that include elements to assure safe use (ETASU) before or after drug approval. REMS ETASU programs cannot, however, replace pre-market drug safety evaluation studies nor should they delay patient access to orphan drugs.
O’Connell and Pariser highlight the challenges to assess orphan drug risk and safety profiles, since they are invariably based on incomplete and sparse data. The authors observed that safety labels for orphan drugs rarely required modifications following post market safety evaluations. They believe, therefore, that higher proportions (in terms of disease prevalence) of patients in orphan drug clinical trials than in common disease drug trials may compensate for the lack of pre-market data available for orphan drug evaluation.
Rare disease patients, their families and physicians often tolerate higher risk uncertainty concerning orphan drug use, because an alternative is usually unavailable. Nevertheless, the authors believe that orphan drugs are generally and should systematically be assessed according to rigorous safety evaluation procedures. They recommend that orphan drug developers and regulatory agencies apply all necessary and appropriate methods to obtain a maximum amount of orphan drug safety data without impeding on patient access to these treatments.