Research Letter Suggests That Off-label Use May Be Boosting Eculizumab Sales

Since its initial approval by the FDA in 2007, eculizumab (Soliris) has gathered a total of 4 indications, and it brought in sales of $3.5 billion in 2018. One of the most expensive drugs in the world, the C5 complement inhibitor targeted by multiple biosimilar development projects has long raised concerns about cost.

In a research letter appearing this week in JAMA Internal Medicine, authors from Oregon Health and Science University raised the question of whether the “large and increasing revenue from eculizumab” could be tied to off-label use for non-approved indications.

Using ClinicalTrials.gov, Google Scholar, and PubMed, the authors identified studies of eculizumab, and reviewed all articles published before February of this year.

They found that there were 372 publications, which included just 22 published clinical trials and 39 observational studies. The remaining 311 publications were case reports or case series. Most of the clinical trials (77%) included fewer than 50 patients.

Publications reported on studies in 39 different indications, including hematological disorders, autoimmune disorders, transplant-related indications, and renal disorders.

Publications for just 2 of the FDA-approved indications, paroxysmal nocturnal hemoglobinuria and myasthenia gravis, were available, and 27 of the 39 indications studied had no randomized clinical trials published.

The authors of the letter write that, in other drugs, prior research has demonstrated that exploratory postapproval trials for unapproved indications have led to widespread use of products in indications where they have not been proven to be effective.

According to the authors, more research is warranted to determine what proportion of revenue related to eculizumab is from off-label versus on-label use, and “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.”

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.