TRENDS & PERSPECTIVES
In August, FDA updated the labeling for the ubiquitous blood-thinner warfarin to include genetic testing information, saying the information can help physicians determine the safest starting dose for their patients.
A month later, the agency approved a genetic test made by Nanosphere Inc. (Northbrook, IL) that can reveal which patients have some variations in two genes, CYP2C9 and VKORC1. Clinical studies have shown that patients with variations in those genes may need a lower dose of the anticoagulant, which is sold under the trade name Coumadin by Bristol-Myers Squibb (Princeton, NJ) and in other generic forms.
This was not the first time that genetic information has been cited in prescription drug labeling. It can be found in a handful of other labels, including the oncology drugs irinotecan for colon cancer and 6-mercaptopurine for acute lymphatic leukemia.
However, this is the first time that pharmacogenomic information has been included in a drug as widely used as warfarin. It is estimated that between 300,000 and 500,000 new prescriptions for warfarin are written every year, while between 2 million and 5 million people are taking the drug every day.
Larry Lesko, PhD, director of the office of clinical pharmacology at FDA’s Center for Drug Evaluation and Research (CDER), said the agency’s updating warfarin labeling was significant because “it means that personalized medicine is no longer an abstract concept, but has moved into the mainstream where it is recognized as a factor in a product used by millions of Americans.”
FDA stopped short of saying that physicians must perform genetic tests before prescribing warfarin. FDA needs more definitive information to make it a directive, said Dwaine Rieves, MD, acting director of the division of medical imaging and hematology products at CDER.
However, Rieves agreed that FDA’s move signifies that personalized medicine is clearly on its way. “We are at the early stages of the use of these types of tests in clinical practice…and it represents an exciting chance,” he said.
Richard S. Schifreen, PhD, vice president of research products at Mirus Bio Corp. (Madison, WI), also sees the regulatory agency’s move as helping to accelerate the acceptance of companion diagnostic tests. “It is one in a series of steps that FDA has taken to encourage the IVD industry to develop companion diagnostics that will assist physicians in identifying patients most likely to benefit from a particular drug,” he said.
Schifreen expects that including pharmacogenomic information in the labeling for a drug as commonly prescribed as warfarin will also create new markets for such testing.
Schifreen added that it is interesting that FDA is in the forefront of this issue, while the pharmaceutical industry has been reluctant to embrace the new model. Still, he said, “I continue to believe that personalized medicine, including companion diagnostics, will improve medical care and will ultimately be adopted. It will just take more time than initially expected.”
Some industry observers also believe that even though the updated labeling is not a directive, its being there will encourage many physicians to include the genetic component in their initial dosing decisions.
Emily Winn-Deen, PhD, vice president of strategic planning and business development at Cepheid (Sunnyvale, CA), said determining proper dosing for warfarin is not easy, so she suspects “many physicians will be willing to adopt something that gets them to the right place faster.”
Winn-Deen also said that medical liability could be a factor. “If this labeling is in the drug, and a patient has a bleed or a clot because his physician had not gotten to the right dose quickly enough, the physician could fear he may have some liability.” They may order the genetic test to cover themselves, she said.
However, others believe FDA has moved too quickly and without sufficient evidence to support including genetic testing information in warfarin’s labeling.
Ann K. Wittkowsky, PharmD, director of anticoagulation services at the University of Washington Medical Center (Seattle), said pharmacogenics is “a fascinating science,” and “one that holds a lot of promise.” However, she said, “it’s just a bit premature to suggest there’s a purpose for it in clinical medicine right now.”
Wittkowsky said that physicians are not likely to embrace the recommendation until a prospective, randomized trial comparing traditional dosing with genetic-based dosing is completed, and they can clearly see which method is best.
