The International Serious Adverse Event Consortium (iSAEC) is a nonprofit organization founded in 2007. It is comprised of leading pharmaceutical companies, the Wellcome Trust, and academic institutions; with scientific and strategic input from the U.S. Food and Drug Administration (FDA) and other international regulatory bodies. The mission of the iSAEC is to identify DNA-variants useful in predicting the risk of drug-related serious adverse events (SAEs).
Patients respond differently to medicines and all medicines can have side effects, in some people. The iSAEC’s work is based on the hypothesis that these differences have (in part) a genetic basis, and its research studies examine the impact genes can have on how individuals respond to a large variety of medicines. The iSAEC’s initial studies have successfully identifying genetic variants associated with drug-related liver toxicity (DILI) and Serious Skin Rashes (SSR). The majority of the iSAEC’s genetic findings to date have been specific to a given drug versus across multiple drugs. However, a number of cross drug genetic alleles are starting to emerge that may provide important insights into the underlying biology/mechanism of drug induced SEAs (e.g. HLA*5701 or UGT1A1*28). Our findings clearly demonstrate an important role for the MHC genomic region (Chromosome 6), in the pathology of immunologically mediated SAEs such as DILI and SSR. They also emphasize the importance of immune regulation genes, in addition to a number of well characterized drug metabolism (ADME) genes.
In the iSAEC’s second phase (2010-2012) our goal is to deepen our understanding of the genetics of immunologic influenced SAEs, including SSR, DILI, and acute hypersensitivity syndrome (AHSS). We will continue to apply novel genomic methodologies to fulfill these aims, including whole genome genotyping and next generation sequencing to explore the role “rare” genetic variants in drug induced SAEs.
The iSAEC collects already available SAE data from the participating pharmaceutical companies and academic institutions into streamlined databases. These well-characterized databases of DNA from individuals who have experienced drug-related a drug related SAE are then being compared with control cases to identify genetic variants that may be associated with the specific SAE. The identification of such genetic variants is believed to be essential to develop safer drugs while also identifying patient populations for whom a medicine will have the greatest likelihood of providing medical benefits with the fewest risks.
The iSAEC builds partnerships with private and governmental research/regulatory institutions, on a global basis, to further its research goals.