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located within SLCO1B1 on chromosome 12, what is strongly associated with an
increased risk of statin-induced myopathy. SLCO1B1 encodes the organic anion-
transporting polypeptide OATP1B1, which has been shown to regulate the hepatic
uptake of statins. Genotyping these variants may help to achieve the benefi ts of
statin therapy more safely and effectively (SEARCH Collaborative Group 2008 ).
The fi nding raises hope that a test could be developed to screen patients to fi nd out
who is at greatest risk for developing this adverse reaction. SINM PhyzioType
System, which is in development, consists of four tests that predict LDL lowering
and HDL raising capabilities, myalgia, and creatine kinase activity in response to
statins. The goal is to enable clinicians to deploy a genetic decision support system
to manage statins, prescribe these drugs on a DNA-guided, personalized basis, and
effectively lower the risk of cardiovascular disease for each patient. Although there
is a statin-gene association for myopathy in the case of some statins, the usefulness
of this information still needs to be proven (Giorgi et al. 2011 ).
FDA Consortium Linking Genetic Biomarkers to Serious Adverse Events
The FDA’s has created a consortium with members of the pharmaceutical industry
and academia that aims to observe how genetic biomarkers contribute to serious
adverse events (SAEs). SAE consortium (SAEC) will be part of the Offi ce of
Critical Path Programs. Some people are genetically predisposed to have SAEs to
some drugs, and the FDA is of the opinion that it not in its best interests of the
patients that the drug manufacturers simply launch these products without putting
appropriate information on labels. SAEC also plans to consult the European
Agency for the Evaluation of Medicinal Products and other national regulatory
bodies for guidance.
Member organizations of the SAEC ( http://www.saeconsortium.org/ ) include
Abbott, GlaxoSmithKline, Johnson & Johnson Pharmaceutical Research &
Development, Pfi zer, Roche, Sanofi -Aventis, Wyeth, Newcastle University,
DILIGEN (a UK program that is developing a test to identify patients at high risk
of developing drug-induced liver disease), EUDRAGENE (a European academic
consortium conducting research on drug-related liver toxicity), Illumina, and
Columbia University (New York). The companies are paying $500,000 each to be
involved in the consortium. Some pharmaceutical companies are skeptical and will
not join as they think that the consortium will have little effect on tracking and
avoiding SAEs. The problem is that it will take thousands and thousands of patients
to screen in order to validate a particular marker. SAEs, which include hepatotoxic-
ity, rabdomyolysis, and QT prolongation, among others, typically occur in less than
one in 1,000 patients and are inherently unpredictable either by preclinical or clini-
cal development. Because of the rarity of such events, the prospect of predicting
them by genetic biomarkers is viewed as not only daunting but unlikely.
Nevertheless, SAEC is grappling with a central challenge of drug development: the
fact that SAEs affecting only a few patients can hold up or prevent the release of a
drug that could help many.
4 Pharmacogenetics