2 October 2007
Seven major pharmaceutical companies have joined with academic centres, the US Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) to form a new group, the International Serious Adverse Events Consortium (SAEC). The SAEC will work together to seek genetic markers that can predict which individuals are at risk of serious side-effects from a given drug or drug class (see press release).
The group intends to begin with studies to identify genetic markers associated with two forms of adverse effect that can result from the use of multiple different drugs, drug-related liver toxicity and a drug-related skin reaction known as Stevens-Johnson Syndrome (SJS), which can in extreme cases be fatal. These side-effects are very rare, such that no single company has enough pharmacogenetic data to identify common genetic factors in affected trial subjects.
Research will be performed by academic centres and external contractors, but funded by the companies (Pfizer, Abbott, GlaxoSmithKline, Johnson & Johnson, Roche, Sanofi-Aventis and Wyeth, each contributing around $1 million annually). The projects will rely on DNA samples from European research consortia Diligen and Eudragene, taken from individuals affected by the adverse drug events (ADEs) in question, which will be used for genome-wide searches of around one million genetic markers to identify any that are associated with the ADEs. It is intended that results will be made publicly available, so that any company could develop pharmacogenetic tests based on the results.
The benefit to the major pharma companies may be the potential to get effective drugs approved for use in restricted populations, if by excluding individuals who are genetically predisposed to extreme drug reactions from receiving the drugs, they are able to demonstrate acceptable efficacy and safety in clinical trials. Pfizer representative Duncan McHale reportedly said: “We have to remove drugs that are clearly offering patients benefits because a handful are getting these severe adverse reactions” (see Pharmalot news). However, pharmacogenetic tests to identify at-risk individuals are often not economically viable, even if suitable genetic markers are identified; most companies would prefer to develop drugs that affect different pathways in the body and do not risk serious ADEs in any recipients.