Is Eculizumab (Soliris®) Being Used Off-Label in Other Indications?

Nov 3, 2019 | Indication, Off-Label, Price Watch

Is Eculizumab (Soliris®) Being Used Off-Label in Other Indications?

Oregon Health and Science University researchers studied the use of eculizumab (Soliris®) and consider that rising revenues could possibly be tied to off-label use for non-approved indications. An award-winning drug, Eculizumab is one of the more-pricey treatments and a target of biosimilar development.

The Research

Published in JAMA Internal Medicine, the research team from Oregon Health and Science University (OHSU) used, Google Scholar and PubMed to identify studies of eculizumab reviewing in the process, all articles and reports published prior to February of 2019.


Out of 372 publications, which included just 22 published clinical trials and 39 observational studies, the remaining 311 publications were case reports or case series. 77% of the clinical trials included less than 50 patients.

The studies included 39 different indications from hematological disorders to autoimmune disorders to renal disorders. Publications for just two of the FDA-approved indications including 1) paroxysmal nocturnal hemoglobinuria and myasthenia gravis were available and 27 of the 39 indications studies had no randomized clinical trials published.

The Problem of Selling Drugs Off-Label

The OHSU authors noted in the report that prior research demonstrates that exploratory post approval trials for unapproved indications may lead to widespread use of drugs in indications where they have not been proven to be effective—yet of course drive up drug product revenue for the biopharmaceutical manufacturer.

The OHSU team believes, according to the Center for Biosimilars story, that additional research should probe in more detail the details of the eculizumab  sales growth—e.g. off-label versus on-label and note “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.” Put simply—the sales should be associated with approved indications associated with FDA-associated randomized controlled trials.

What is Eculizumab?

Sold under the trade name Soliris® among others, it is a medication approved by the FDA in 2007, gathering 4 indications along the way accumulating in $3.5 billion in sales in 2018. It is one of the most expensive drugs in the world according to the Center for Biosimilars.  Eculizumab is a first-in-class terminal complement inhibitor discovered, developed and commercialized by Alexion. The product, according to its maker Alexion, works by selectively inhibiting activation of specific proteins in the complement system (C5a and C5b), which play a role in the treatment of multiple rare diseases.


The drug is indicated for 1) paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, 2) the treatment of patients with atypical hemolytic uremic syndrome (aHUS), to inhibit the complement-mediated thrombotic microangiopathy, 3) the treatment of adult patients with generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody positive and 4) neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive. Alexion reports it is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS). Moreover they warn that it is not know if Solaris is in fact safe and effective in children with PNH, gMG or NMOSD.

Price Watch

An award winning drug, it had patent exclusivity till 2017. Alexion was able to start selling the drug in 2007 and made $295 million by 2008. By 2010 it had been associated with being the world’s most expensive drug costing $409,000 per year in the U.S. by 2010. By 2015, it was the fifth most expensive medication in the U.S. based on a cost per person treatment basis.

Lead Research/Investigator

Kim S. Myung, MD, Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University

Vinay Prasad, MD, MPH, Department of Public Health and Preventive Medicine, Oregon Health and Science University

Source: JAMA Network


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