Characteristics of Clinical Trials to Support Approval of Orphan vs Nonorphan Drugs for Cancer

Orphan drugs—drugs that are developed to treat rare diseases—get special consideration from the Federal Drug Administration (FDA). The Orphan Drug Act of 1983 provides incentives to drug manufacturers, including waiver of drug application fees and faster FDA approval.

Researchers looked at 15 orphan drugs approved to treat 14 cancers and compared them to 12 nonorphan cancer drugs. They examined dates of applications and filings with the FDA as well as letters of approval by the FDA. They reviewed clinical trial designs and whether or not the trials included comparators, adverse events, deaths and dropouts.

The median total clinical testing phase for orphan drugs was 5.1 years compared to 6.9 years for nonorphan drugs. The FDA review time from submission of a new drug application to final approval was nearly identical (6.2 months orphan; 6.1 months nonorphan).

Compared to nonorphan drug trials, pivotal clinical trials of orphan drugs were less likely to be randomized and blinded. Patients had higher rates of serious adverse events for studies of orphan drugs when compared to nonorphan ones.

Given the findings, the authors recommend that the Orphan Drug Act be amended to ensure products are rigorously evaluated and to encourage development of first-in-class drugs.