NEW YORK (GenomeWeb News) — Twelve drug makers, including six top-10 pharma companies, signed up as “formation members” of what is being called the Severe Adverse Event Consortium, a far-reaching project to identify genetic biomarkers that might predict serious adverse events, according to a recent presentation made by its chairman.
Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Lilly, Merck, Novartis, Pfizer, Roche, and Wyeth were listed as “formation members” of the consortium, which aims to “identify and validate” DNA variants that are “clinically useful” in predicting the risk of drug-induced serious adverse events.
The disclosure was made March 6 by Arthur Holden, chairman of the =Consortium and senior vice president of corporate and market development at Illumina, during a presentation at a conference sponsored by management and technology consulting firm Diamond.
As part of the project, the drug makers have put up $500,000 apiece for a total
$6 million so far, according to Paul Watkins, director of the Genetic Clinical Research Center at the University of North Carolinas, Chapel Hill, and a participant in the consortium. The consortium is a public-private endeavor, and it remains unclear how much funding will come from public sources, or who those sources will be.
As GenomeWeb Daily News reported last week, officials expect the consortium, which will look at adverse events such as hepatotoxicity, rhabdomyolysis, and QT prolongation, to be operational in the next few weeks.
Watkins yesterday told GenomeWeb Daily News that the consortium will initially try to tackle liver toxicity, and plans to develop a DNA chip for the indication by the end of the year.
In his presentation, Holden, who is also chairman of the Pharmaceutical Biomedical Research Consortium and was chairman and CEO of the SNP Consortium, said the goals of the SAE Consortium are to establish a “coordinated network for obtaining well characterized SAE cases and controls;” “define the required content for an optimal SAE genotyping panel;” develop computational methods to “effectively apply whole-genome analysis to SAE marker development;” create a publicly available “knowledge base to help predict key SAEs across all drugs;” and manage IP relating to markers useful in predicting SAEs “to ensure broad and open access.”
Academic members of the consortium include Eudragene, a European collaboration to establish a case-control DNA collection to study the genetic basis of adverse drug reactions; Diligen, a UK Department of Health-funded program that aims to develop a test to identify patients at high risk of developing drug-induced liver disease; and the Drug-Induced Liver Injury Network, an NIH-funded program created to research the causes of drug-induced liver disease; among others.
The number of drug makers that have signed on to the consortium is noteworthy because the industry and the US Food and Drug Administration, which Holden also described as a formation member, have been criticized recently for marketing drugs with safety issues.
The creation of the organization is particularly timely. A study in the New England Journal of Medicine this week linked GlaxoSmithKline’s diabetes drug Avandia to a potentially significant increase in the risk of heart attack and heart-related deaths.
In a statement released yesterday, the FDA said it “is aware of a potential safety issue related to Avandia” but stressed that “other published and unpublished data from long-term clinical trials of Avandia … provide contradictory evidence … “
The agency also said its analyses of these data are ongoing. The FDA “has not confirmed the clinical significance of the reported increased risk in the context of other studies,” the agency said in its statement. “Pending questions include whether the other approved treatment from the same class of drugs, pioglitazone, has less, the same or greater risks.”
In response to the NEJM article, Glaxo said it “strongly disagrees with the conclusions” of the paper, which it said “are based on incomplete evidence and a methodology that the author admits has significant limitations.” Glaxo is an SAE Consortium formation member, according to Holden’s presentation.
Also, in 2005, the FDA released an alert saying that certain statin drugs, including AstraZeneca’s Crestor, are associated with rhabdomyolysis. “To date, it does not appear that the risk is greater with Crestor than with other marketed statins,” the FDA said in its alert.
However, the agency decided to update Crestor’s label “to highlight important information on the safe use of Crestor to reduce the risk for” rhabdomyolysis. AstraZeneca is also an SAE Consortium member, according to a company spokesperson.
The consortium’s aims dovetail with those of the FDA, which said in a recent fact sheet that it is “acting in a scientific advisory role” and is “providing guidance on the establishment” of the consortium.
Wendy Sanhai, senior scientific advisor in the FDA’s Office of the Commissioner, told GenomeWeb Daily News last week that understanding SAEs “is a huge unmet public health need” and has been a “huge priority for some time” at the FDA.
According to Holden’s presentation, the US healthcare system spent around $177 billion, or 10 percent of its total healthcare costs that year, on treating drug-related mortality and morbidity. He also reported that adverse drug reactions “are believed to cause” more than 200,000 deaths each year in the US, which he said places them among the top-10 causes of death.
According to the FDA’s “Drug Safety Initiative” fact sheet, the consortium is meant to “identify and qualify biomarkers for adverse events, including pharmacogenetic markers and identifiers; leverage/establish appropriate databases and repositories; coordinate the development of common research platforms, nomenclature, and standards; and establish effective intellectual property and data-pooling strategies.”
Holden declined to comment for this article. Officials from 11 of the 12 member drug makers did not return calls sekking comment.