The New Paradigms in Clinical Research: From Early Access Programs to the Novel Therapeutic Approaches for Unmet Medical Needs

Abstract

Despite several innovative medicines gaining worldwide approval in recent years, there are still therapeutic areas for which unsatisfied therapeutic needs persist. For example, high unmet clinical need was observed in patients diagnosed with type 2 diabetes mellitus and hemophilia, as well as in specific age groups, such as the pediatric population. Given the urgent need to improve the therapy of clinical conditions for which unmet clinical need is established, clinical testing, and approval of new medicines are increasingly being carried out through accelerated authorization procedures. Starting from 1992, the Food and Drug Administration and the European Medicines Agency have supported the so-called Early Access Programs (EAPs). Such procedures, which can be based on incomplete clinical data, allow an accelerated marketing authorization for innovative medicines. The growth in pharmaceutical research has also resulted in the development of novel therapeutic approaches, such as biotech drugs and advanced therapy medicinal products, including new monoclonal antibodies for the treatment of asthma, antisense oligonucleotides for the treatment of Duchenne muscular dystrophy and spinal muscular atrophy, and new anticancer drugs that act on genetic biomarkers rather than any specific type of cancer. Even though EAPs and novel therapeutic approaches have brought huge benefits for public health, their implementation is limited by several challenges, including the high risk of safety-related label changes for medicines authorized through the accelerated procedure, the high costs, and the reimbursement and access concerns. In this context, regulatory agencies should provide the best conditions for the implementation of the described new tools.

FDA and EMA Approvals of New Breast Cancer Drugs—A Comparative Regulatory Analysis

“…Furthermore, we found that the rate of new drug approvals for breast cancer has dramatically increased over the last 30 years, compared to earlier decades, in part driven by the development of targeted therapeutics [3]. This trend matches the acceleration of new drug approvals seen across the field of oncology as a whole [4,5], which results from the impressive progress in translational cancer research and from the evolving regulatory environment [6,7]. Together, these factors have profoundly changed the way in which new cancer drugs are discovered, studied, reviewed, and approved [8][9][10].…”

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database

“…Given the clinical relevance of irADRs and considering that innovative drugs are increasingly authorized by accelerated procedures (Scavone et al, 2017b;Scavone et al, 2017a), further safety investigations in real-life context are necessary (Scavone et al, 2019). We believe that our results could be shared with clinicians that dailies prescribe and administer ICIs or monoclonal antibodies in general.…”

Precision Dosing Priority Criteria: Drug, Disease, and Patient Population Variables

“…Disease state is one of the most important factors to consider when determining if a drug should be prioritized for precision dosing. The integration of precision dosing is likely to be most helpful in areas of high unmet medical need (Darwich et al, 2017), which include infectious disease, hematology, immunology/transplantation, oncology, neurology, and other therapeutic areas noted by Scavone and colleagues (Scavone et al, 2019). Disease related morbidity, mortality, and progression can be quite variable and can greatly impact the need for drug dosing individualization.…”