Orphan Drug May Be Frequently Used Off-Label, Inflating Revenue, Letter Suggests

Although eculizumab is only approved by the FDA to treat 3 rare indications, the high and increasing net sales for the drug have raised concerns about off-label use, according to a research letter in JAMA Internal Medicine. Past research from America’s Health Insurance Plans had found that revenues for orphan drugs “primarily come from their non-orphan and off-label use.”

When the drug was first approved in 2007 to treat paroxysmal nocturnal hemoglobinuria (PNH), eculizumab was the costliest drug in the world with a $400,000 per year price tag. The monoclonal antibody has since been approved for atypical hemolytic uremic syndrome and refractory generalized myasthenia. All 3 indications are for rare diseases and eculizumab was granted orphan designation by the FDA for each indication.

Since 2007, worldwide net sales for the drug have increased from $66 million to more than $3.5 billion in 2018, raising the question of whether the drug was being used off-label for non—FDA-approved indications. In addition to identifying off-label use, the researchers were trying to ascertain the evidence that would support such use.

The researchers from Oregon Health and Science University searched the keyword “eculizumab” on ClinicalTrials.gov, Google Scholar, and PubMed to identify clinical trials and noninvestigational studies. They extracted data on the size of the study, type of study, data of study, and clinical indication of the drug.

A total of 322 publications were included and most had more than 50 patients (77%). The studies used eculizumab for 39 distinct indications and only PNH and myasthenia gravis had confirmatory trials. For nearly all indications, there were no randomized controlled trials in the literature.

The authors suggested that future research should try to quantify how much of eculizumab’s annual revenue is tied to off-label use versus use for FDA-approved indications.

“…patients and clinicians should be aware that the evidence supporting off-label use consists mostly of case series/case reports, along with small observational and interventional studies,” the authors wrote.

Reference

Kim MS, Prasad V. The clinical trials portfolio for on-label and off-label studies of eculizumab [published online October 28, 2019]. JAMA Intern Med. doi:10.1001/jamainternmed.2019.4694.