Guerbet Statement Following Medical Imaging Drugs Advisory Committee September 8, 2017
Princeton (NJ, USA)
Magnetic resonance imaging (MRI) is a widely used diagnostic procedure which is critical to patient health. And vital to MRI are the contrast agents that give physicians a sharper, more accurate picture of tissue than they would otherwise be able to have.
There are two kinds of gadolinium based contrast agents (GBCAs), linear and macrocyclic. Although there are many similarities amongst these agents, they differ in their kinetic and thermodynamic stability. Linear GBCAs are generally less stable, and for this reason, more likely than macrocyclic agents to deposit gadolinium in tissue. Guerbet’s GBCA, Dotarem® (gadoterate meglumine) is a macrocyclic agent.
In light of the importance of contrast enhanced MRIs to patient health, Guerbet is strongly committed to ensuring that this critical diagnostic tool remains available as a safe and effective option for physicians.
However, Guerbet notes that evidence supports precautionary measures primarily with respect to linear agents. As recent evidence has raised the possibility that repeated use of linear agents might lead to a much higher propensity for gadolinium deposits in tissues, the risk mitigation measure Guerbet proposed to the FDA is to comply with the National Institutes of Health (NIH) approach, and to use linear GBCAs only in cases where there is no alternative.
The clinical significance of gadolinium retention in the body and the brain is still unknown. Until evidence definitively dispels any lingering concerns about the safety of GBCAs as a whole, Guerbet supports taking precautions when using them in patients who will need multiple injections during their lifetime and in fragile populations (children and renal impaired patients). We also support using contrast agents at the lowest diagnostic dose.
Guerbet notes that, to date, there is no evidence of gadolinium accumulation in the brain or other tissues after repeated administration of its macrocyclic product, Dotarem® (gadoterate meglumine). It is due to this that we have seen an increased demand for macrocyclics in the markets. Guerbet has previously announced it will globally phase out its linear agent, Optimark® (gadoversetamide injection). Before this decision, Guerbet voluntarily proposed a label change in the US regarding linear agents’ potential for gadolinium deposition. Guerbet was the only GBCA manufacturer to do so.
Guerbet appreciates the discussion of today’s Medical Imaging Drugs Advisory Committee and will continue to work with the FDA to further understand the mechanisms and consequences of gadolinium deposition in tissue.