SJS and TEN are serious reactions to medication that present with a rash on the skin that blisters over causing the skin to keep off in sheets. Mucus membranes such as those on the eyes and in the mouth also can blister, leading to life-threatening complications. If signs and symptoms are not quickly recognized and the medication causing the problem not identified and stopped, the reactions can be fatal.

SAEC is a nonprofit organization made up of major pharmaceutical companies and academic institutions focused on research relating to the genetics of drug-induced serious adverse events. Organized 16 months ago, the group’s mission is to develop genetic tests that can identify which patients are more likely to suffer severe adverse reactions to medication. Much of the group’s focus is on SJS/TEN.

The group’s findings were derived by pooling serious skin rash cases and control samples from GlaxoSmithKline plc London, U.K. From that data, researchers identified numerous genetic associations that may increase one’s chances of having a serious skin reaction to medication.

“This consortium has taken a significant step forward by promoting open sharing of drug safety data. This type of cooperation has the potential to lead to more personalized approaches to medicine that can reduce a patient’s risk for experiencing an adverse drug event,” said Janet Woodcock, M.D., director, the FDA’s Center for Drug Evaluation and Research.

The group’s initial research results will be published later this year.

SOURCE: Stevens Johnson Syndrome › SAEC releases first data on serious adverse events caused by drugs

Currently, the SAEC is conducting a study that addresses Stevens Johnson Syndrome (SJS). SJS is a rare but life-threatening reaction to medication. SJS affects the skin and mucus membranes, causing blisters to form on the skin and the skin to peel off in sheets. Blisters also can form on the mouth and eyes, causing serious eye complications and even blindness. SJS is linked to more than 200 medicines. Most often SJS is linked to ibuprofen, antibiotics and anti-seizure medication.

Researchers for the SAEC project will look for genetic variations linked with SAEs from the SNP Consortium and the Human Genome Project’s Hap Map Project.

“The traditional research model only provides one piece of the puzzle in understanding the genetic variations that could lead to an increased risk of an adverse event. Because of the number of patients needed to tie a genetic variant to an SAE, and the resulting cost of doing these studies, no one company, research center, or agency can efficiently conduct this research on its own. The most efficient way to study drug-related SAEs is to create a global, publicly available ‘knowledge base’ that will help identify the genetic variations that may predict SAEs,” SAEC Chairman and CEO Arthur Holden said in a September 2007 announcement in Highlight Health, when the consortium was formed.

The SAEC research study will be made available within 12 months of completion. If initial studies are successful, the consortium vows to study every major SAE to find its genetic cause.

SOURCE: Stevens Johnson Syndrome › Consortium studies genetic markers, hopes to predict SJS

“SAEC’s focus is to identify and to validate DNA variance or genetic markers that are useful in predicting a drug-induced serious adverse event,” Arthur Holden, the chairman of the group, said during a midmorning teleconference Thursday.

The findings of the consortium could have an impact on improving the ability of patients to safely use existing drugs, Holden added. “We hope it will improve the productivity and effectiveness not only for those who develop drugs but for those who regulate drug development,” he said.

“The immediate goal would be to develop a test that could identify who will have a problem with a drug before they get it,” said Dr. Paul Watkins, director of the General Clinical Research Center at the University of North Carolina in Chapel Hill. “The ultimate goal is to look at the genes that are causing the susceptibility and work back to figure out how we can design drugs differently so that no one would have that problem,” he added.

“The two drug reactions that are being studied, Stevens-Johnson and liver toxicity, are very common reasons for problems with drugs either being restricted, not being developed, not being approved or being pulled off the market,” said Dr. Janet Woodcock, Deputy Commissioner and Chief Medical Officer at the U.S. Food and Drug Administration.

“This effort is part of personalized medicine — personalized safety — that will make treatments safer by understanding individual benefits and risks,” she added. “This will help in the development of drugs both in avoiding these side effects in the future and maybe developing tests to help identify people at high risk,” she said.

Findings from these studies could lead to the FDA requiring genetic tests to determine risk before the drug is prescribed, Woodcock added.

A recent survey found that most Americans are more concerned with drug safety than with speeding more medications to the marketplace.

Members of the consortium include Abbott, GlaxoSmithKline, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Pfizer, Roche, Sanofi-Aventis and Wyeth. In addition, the FDA will consult on the design and conduct of SAEC studies.

The actual research will be done at academic centers in Europe and the United States.

The results of the studies will be made public domain, and none of the companies will have early access or be allowed to patent the findings. When the results are made public, any company can develop and sell the genetic tests that predict side effects.

SAEC is one of several consortiums formed by the pharmaceutical industry to conduct basic research. One of the first was started in 1999 and was headed by Holden. That consortium looked for DNA variations among people. Their data were also put into the public domain.

October 17th, 2007

SOURCE: Stevens Johnson Syndrome › Drug industry seeks tests to spot side effect risks