However, we note that the positive benefit-risk balance was confirmed for a limited patient population - patients suffering from paroxysmal and persistent atrial fibrillation. Moreover, the agency said that Multaq should be used only after other treatment options have been considered. Furthermore, Multaq is not recommended for use in patients with left ventricular systolic dysfunction or patients with current or previous episodes of heart failure.
Sanofi’s Multaq was initially being reviewed by the EMA’s Committee for Medicinal Products for Human Use (CHMP) from January 2011 due to reports of severe liver injury. However, the scope of the review was expanded in July 2011 following the discontinuation of the PALLAS phase IIIb trial which was being conducted in patients with permanent atrial fibrillation.
Sanofi decided to discontinue the study based on recommendations from the study’s Operations Committee and Data Monitoring Committee (DMC). A significant increase in cardiovascular events was observed in the Multaq arm. A higher rate of events and hospitalizations were seen in the Multaq arm compared with placebo. Sanofi said that the decision to terminate the study was not related to any hepatic adverse event.
Earlier, in January 2011, Sanofi had issued a Dear Health Care Professional Letter in the US and EU informing health care providers of several cases of hepatocellular liver injury and hepatic failure in patients receiving Multaq, including two post-marketing reports of acute hepatic failure requiring transplantation.
Moreover, the US Food and Drug Administration (FDA) issued a Drug Safety Communication on hepatic events reported in patients treated with Multaq. In February 2011, both the EU Summary of Product Characteristics and US Prescribing Information were updated to include liver function monitoring.
More than 400,000 patients across the world have been treated with Multaq. Multaq sales were €172 million in 2010. We believe sales will be hampered with the inclusion of additional restrictions in the product label.