Washington Editor

Several large drug manufacturers and academic institutions have banded together on a project to examine the impact genes play on how people respond to medications and identify genetic markers that may help predict who may be at risk for serious drug-induced adverse events.

The group, dubbed the International Serious Adverse Events Consortium, or SAEC, is hoping its project can help prevent exposure to drugs that otherwise are safe for the majority of the population but are dangerous to people with a certain genetic make-up, SAEC Chair Arthur Holden told reporters during a media briefing on Thursday.

"It's a true tragedy," said Paul Watkins, director of the General Clinical Research Center at the University of North Carolina at Chapel Hill, when a drug is in the last stages of development and near approval and "the whole program is closed down because one or two people develop a serious and potentially life-threatening reaction."

Many "good drugs" have been removed from the market or had restrictions imposed by regulators because "a tiny number of people" have had adverse reactions to the products, added Janet Woodcock, deputy commissioner and chief medical officer at the FDA.

"FDA has been struggling for three decades with serious adverse reactions to drugs, and up to this point, in most cases, these were all considered idiosyncratic. In other words, we had no idea why they came about," she said. But, Woodcock said, as an outgrowth of the new science of genomics, "we are actually able to test and to try to determine if there is genetic predisposition."

Genomics, she said, already is playing a role in identifying patients at risk for adverse events who take certain drugs.

The FDA in August asked makers of warfarin to include a warning in labeling that patients with certain gene types are at a greater risk for bleeding. The agency recently approved a genetic test to specifically identify patients at risk for adverse events to warfarin.

The SAEC is being funded by seven drug firms that are partnering on the project: Abbott, GlaxoSmithKline plc., Johnson & Johnson, Pfizer Inc., Roche Holding AG, Sanofi-Aventis SA and Wyeth.

So far, the firms have contributed millions of dollars, Holden said. However, he would not specify the amounts each company has contributed to the project.

He noted that the group is "in the process of working to add additional members," including large HMOs and clinical research groups.

The FDA, not an official member, is providing input and will have access to the information derived from the project.

The results from SAEC research studies will be made available to the research community for further study, Holden said.

While the consortium's immediate goal is to predict who may have a problem with a certain drug before that person is exposed, the ultimate ambition of the project is to identify the genetic variations that are causing the susceptibility to adverse events and "work back and figure out how we can design drugs differently so that no one will have that problem," said Watkins, an expert in hepatology who is acting as a consultant for the group.

The SAEC's first two research programs, Holden said, will address drug-related liver toxicity and a rare but serious drug-related skin condition called Stevens-Johnson syndrome (SJS).

"Our research activities are focused on two specific areas initially, but our research objective overall is quite broad," he said. "We want to look across the entire spectrum of drug-induced serious adverse events over time. But you have to start somewhere."

SAEC chose liver toxicity and SJS as its first focus because DNA samples and other data already exist in those two areas, which allows the project to quickly move forward and generate results sooner, Holden said.

The Stevens-Johnson syndrome project, he noted, is being enabled by a "significant contribution from GlaxoSmithKline of a well-characterized group of patients who have had this syndrome across over 30 medications."

The analysis and coordinating capability for that part of the project, Holden said, will be housed at Columbia University. The consortium is using a commercial firm, N.C.-based Expression Analysis Inc., to oversee the genotyping of the SJS project, he added.

San Diego-based Illumina Inc. also is providing clinical research services for the project, Holden noted.

SAEC, Holden said, expects to release data to the public domain from the SJS project by next fall.

The drug-induced liver injury project, he said, is using contributions from two European research networks known as Diligen and Eudragene.

"This is an exciting and pioneering opportunity," Watkins said, calling the information derived from the project a "gift" to the research community.