Benefit-risk balance of orlistat is positive, says EMA
This article was originally published in Scrip
The EMA is satisfied that the benefits of orlistat (Roche's prescription product Xenical and GSK's half-dose OTC version Alli) outweigh the risks for treating obese or overweight patients with a body mass index of 28 KG/m2 or more.
The agency said last year that it would be reviewing the drug following spontaneous reports of severe liver injuries over a number of years (scripintelligence.com, 23 September 2011). The agency's scientific committee, the CHMP looked at all available data on the risk of liver injury and other side effects. This information included post-marketing surveillance, population-based studies in published literature, data from trials supporting marketing authorisation and the results of an "expected versus observed" analysis of reports of severe liver injuries. The latter was carried out by Roche and GSK at the request of the CHMP.
"There was no strong evidence that orlistat increased the risk of severe liver injury, and there was no known mechanism by which orlistat was expected to cause liver disorders," said the agency. According to the committee, the number of reported severe liver reactions was low while there was no pattern seen in the types of problems reported. In most cases, other factors were likely to have caused an increase in the risk of liver, said the committee. "While there may be very rare cases of serious liver injury for which causality with orlistat cannot be excluded, the cases do not provide good evidence of a casual relationship." In addition, the CHMP pointed out that obesity could be linked to a higher risk of lover disease, as shown in population-based studies.
Between August 2009 and January 2011 there were four cases of severe liver injury where the role of orlistat could not be ruled out. These included one fatal liver failure and one case leading to liver transplant. Between 1997 and January 2011 there were 21 cases of severe liver toxicity where Xenical was considered a probable cause, although other factors that could have caused the problems were present, said the agency. There were nine reports of liver failure in patients using Ali between May 2007 and January 2011. Again, the agency said that there could have been other causes and contributing factors.
The agency highlighted that both Xenical and Alli are estimated to have been used by some 53 million patients across the world, including 20 million patients in the EU. "The number of cases needs to be considered in the context of cumulative usage of Xenical and Alli," it said.