1435O_PR - Comparison of the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) in clinical trials supporting US Food and Drug Administration (FDA) approval of orphan vs. non-orphan drugs

Abstract

Background: The Orphan Drug Act provides incentives to manufacturers to develop drugs for rare diseases. The ESMO-MCBS is a validated tool, aimed at quantifying the clinical benefit for cancer drugs. Here, we compare the characteristics of clinical trials leading to approval by the FDA of orphan and non-orphan drugs and apply the ESMO-MCBS thresholds for meaningful clinical benefit. Methods: We searched the [email protected] website to identify anticancer drugs approved between January 2006 and December 2016. These were then categorized as orphan or non-orphan drugs as determined by the FDA. For each drug, we subsequently collected data on clinical trial design and methodology and compared these between orphan and non-orphan drugs. For drugs supported by randomized controlled trials (RCTs), we applied a ESMO-MCBS grade. Comparisons were performed using Mann Whitney U or Chi squared tests. Results: Of the 137 studies included, 109 (80%) were RCTs. These led to the approval of 63 individual drugs for 118 indications. Among these indications, 54 (46%) received orphan drug designation. Compared to non-orphan drugs, trials supporting orphan drugs approval had a smaller sample size (median 369 vs 687, P=.001), were less likely to evaluate experimental cytotoxic chemotherapy or endocrine therapy than targeted therapy (8% vs 21%, P=.005) were less often randomized (73% vs 86%; P=.047) and were more likely to assess intermediate endpoints rather than overall survival (71% vs 51%, P=.01). A similar proportion of orphan and non-orphan drugs approved for palliative use met the ESMO-MCBS threshold for meaningful benefit (29% vs 27%; P=.86). There were too few studies performed in the curative setting (n = 7) to perform statistical testing. Conclusions: Compared with trials used to approve non-orphan cancer drugs, trials for orphan drugs are smaller, more likely to explore experimental biological therapies, use single-arm trials and intermediate end points. A similarly low proportion of approved orphan and non-orphan drugs meet the ESMO-MCBS threshold for meaningful benefit. Legal entity responsible for the study: None Funding: None Disclosure: All authors have declared no conflicts of interest.