Drug Topics - October 22, 2007 - (Page 21)

21 applications for coordinated use of the drug and test. Beyond trastuzumab, however, there are few examples of successful RxDx from beginning to end of development, although numerous projects are currently in the works. For one, Vanda Pharmaceuticals, located in Rockville, Md., has a promising RxDx candidate in its antipsychotic iloperidone. The drug originally belonged to Novartis, but after discovering the drug’s potential to cause QT prolongation—an adverse effect seen with atypical antipsychotics—Vanda decided to drop iloperidone. But that was after the firm had identified a couple of genetic markers linked to the metabolism and response of the drug. At the time, Vanda’s CEO, Mihael Polymeropoulos, headed up Novartis’ global pharmacogenetics department. When he left to form Vanda, he acquired the rights to iloperidone and has since done additional work to prospectively confirm the markers in a phase III trial. According to Vanda, the findings identified a polymorphism that occurs in 70% of patients with schizophrenia and is apparently related to iloperidone response. With respect to the QT interval, Vanda said that the QTc change from baseline averaged 11.4 milliseconds across all patients and that, with the help of a genetic marker, it was determined that prolongation was shorter in patients who were good metabolizers than in poor metabolizers—10.4 milliseconds and 15 milliseconds, respectively. The data on the markers are included with the study results in the NDA package, according to the company, although the markers themselves have not been identified publicly to date. Vanda said that information on the discovered markers will be released at the American Society of Human Genetics annual meeting in San Diego, Oct. 23-27. According to Vanda, in its phase III trial, researchers built a simple blood test and will likely develop a similar test to pair with iloperidone’s launch. Currently Vanda is exploring partnerships for development of this diagnostic. sistance in some big pharma companies to develop companion diagnostics due to internal pressure. Many do not want tests for their drugs because they aren’t sure how the biomarker will affect their sales or whether it would narrow the market for targeted therapies, he explained. He believes, however, that “once people see that biomarkers can increase the efficacy of drugs and reduce the cost of clinical trials,” the companion diagnostic will be the desired approach. Alliance to study genetic markers L Double take According to experts, small companies are not the only ones working on codevelopment. “Practically all the major pharmaceutical companies are talking about and saying they are working with biomarkers, but a couple of things are slowing down their progress,” said Walter P Carney, . Ph.D., in a recent report on oncogenomics. Carney, who is president of Oncogene Science, part of Bayer HealthCare, said that finding the right biomarkers can be a slow process. “We need to remember that developing companion diagnostics with targeted therapies is a relatively new effort that will require additional research to get the right test-therapy combination,” he pointed out. He went on to say in the report that there is also re- ast month, a group of seven pharmaceutical companies, academic institutions, and the Food & Drug Administration announced they would come together to study genetic markers and their links to the serious adverse effects (SAEs) of drugs. Known as the International Serious Adverse Events Consortium (SAEC), the alliance will complete two initial research programs, the first of which will investigate whether gene variations are responsible for the development of StevenJohnson syndrome (SJS), a potentially life-threatening skin rash. In a second study, the group will look at drug-related liver toxicity and test its hypothesis that the adverse effect may have a genetic basis. “We are encouraged that this new consortium will play an important role in enhancing drug safety by accelerating and advancing our understanding of genetic variants associated with these adverse events,” remarked Janet Woodcock, M.D., FDA’s deputy commissioner and chief medical officer. “Given the considerable time, size, and cost of conducting safety studies, a coordinated strategic partnership among industry, academia, and government can more rapidly advance this critical science.” Since the incidence of SAEs is relatively low, SAEC hopes that pooling already-existing data on drug-related liver injury and SJS from participating pharmaceutical companies and research partners will make it easier to predict risk than just looking at each organization’s data individually. The data will then be compared with controls to identify genetic variants that may be associated with SAEs. SAEC chairman and CEO Arthur Holden explained that the number of patients needed to tie a genetic variant to an SAE is so great that the resulting cost of doing these studies is too much for any one research center, company, or agency to undertake. He believes the most efficient way to study SAEs is by creating a publicly available knowledge base that will help identify the genetic variations that may predict adverse events. According to SAEC, to identify the genetic variations linked to SAEs, researchers will use data from the SNP Consortium and Hap Map Genome Project, which mapped single nucleotide polymorphisms, or SNPs, in conjunction with the Human Genome Project. Results will be made publicly available within 12 months of the completion of the study group’s genotyping. SAEC members include Abbott, GlaxoSmithKline, Johnson & Johnson, Pfizer, Roche, Sanofi-Aventis, Wyeth, Newcastle University/DILIGEN, EUDRAGENE, Illumina Inc., Columbia University, and the FDA.

Table of Contents Feed for the Digital Edition of Drug Topics - October 22, 2007

Drug Topics - October 22, 2007 Contents Latebreakers Legislative Victory Builds Momentum for Pharmacy Month Letters Health-System Edition R.Ph.s Brace for Payment Denial for Hospital-Acquired Conditions Topical Human Thrombin Helps Arrest Bleeding FDA Panels Fail to Set Target Levels for Renal Patients’ Hemoglobin Warning Letters Raise Patient Safety Concerns for Fentora Ending/Reversing Weight Gain Man Given Fatal Drug Overdose at Staten Island Hospital Pharmacists Playing More Important Role in Dialysis Treatment AHA President R.Ph.'s Here's How You Can Increase Your Value Premier Launches Comprehensive Quality Improvement Project FDA Approves Dexrazoxane for Treatment of Extravasation New Federal, State Reforms to Ease Disaster Relief Kinks 150 Years of American Pharmacy Ten Tips for MTM Success Independent Superstars: The Ones to Watch The New Dynamic Duo A Parkinson's Disease Primer Classified New Products Advertisers Index Viewpoint

Drug Topics - October 22, 2007

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.