Imbruvica Toxic Side Effects Should Lead FDA to Require Additional Studies To Evaluate Risks: Report

Side effects of the cancer drug Imbruvica have been linked to an increased risk of cardiovascular injuries and death, leading researchers to call for federal regulators to require the drug makers to conduct additional clinical trials.

In an editorial published in the Journal of the American Medical Association (JAMA), several cancer specialists from universities nationwide highlighted the cardiotoxic properties and adverse health effects associated with Imbruvica, citing previous studies which recorded a seven percent fatality rate during treatment.

Imbruvica (Ibrutinib) is a prescription medication used as an inhibitor of Bruton’s tyrosine kinase (BTK). The FDA first approved the drug in 2013, for the treatment of  mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) for patients who had already received at least one prior therapy.

The drug’s use profile was expanded in 2016 for front-line use in the treatment of CLL, becoming the first chemotherapy alternative option of its kind to patients regardless of treatment history.

According to the editorial, while Imbruvica was known to have cardiotoxic properties, likely due to the off-target inhibition of another kinase, initial clinical trials demonstrated increased survival rates among patients.

However, the editorial’s authors highlighted a recent analysis of real-word data gathered by the World Health Organization (WHO), which involved 13,572 cases of patients using the recommended dosage of 560mg of Imbruvica in over 130 countries. As of January 2018, 303 deaths were associated with the use of Imbruvica, in which 103 were due to arrhythmias, and 90 were due to central nervous system hemorrhages.

Additionally, patients experienced a higher rate of cardiac conduction disorders such as atrioventricular (AV) blocks as early as the first dose, with a median onset of 27 days. Researchers noted at least nine fatalities were related to conduction disorders caused by first-use of Imbruvica.

When comparing the data collected from WHO to a Mayo Clinic report, researchers  suggested lowering the 560mg recommended dosing amount could lower the risk of  heart problems and death.

According to the Mayo Clinic study, patients prescribed Imbruvica to treat CLL with initial doses starting at 420 mg, 280mg and 140mg or less per day were associated with a decreased rate of cardiovascular complications and an increased overall survival rate, when compared to patients prescribed the manufacturer recommended 560mg dosage.

Lead author of the study, Mark J. Ratain, MD of the University of Chicago stated the FDA should have required the manufacturer to perform a randomized dose ranging study of Imbruvica years ago, rather than unnecessarily expose patients to cardiac risks attributable to excessive dosing.

Researchers recommend the FDA use its post market regulatory authority to force the drug manufacturer, Pharmacyclics LLC, into performing a randomized dose study.