Pharmacogenetics and Addiction

Patients’ genetic information – the impact it has on their health, implications for disease, and responses to treatments and medications — is helping to power the healthcare locomotive we now call personalized medicine. Laying the track for its expansion is pharmacogenetics, an exploration of how differences in genetics affect both the risk of individuals getting specific diseases during their lifespan and their likely response to drugs.

While it all sounds very cutting edge, the field has been gaining steam for some time. “Pharmacogenetics is a discipline that is already about 50 years old,” said Wolfgang Sadee, DR.rer.nat, via an interview conducted by the American Association of Pharmaceutical Scientists (AAPS). Sadee is a professor and the director of Ohio State University’s program in pharmacogenetics, whose current projects include an investigation of susceptibility genes in drug addiction. “Back then we usually looked at a single gene that could be defective in how it metabolizes a drug in the body. But now we know about all genes in the body and we understand that each drug interacts with numerous proteins in each gene,” he said. “Some diseases that happen later in life are very complex and difficult to treat. Current medications do not work all that well. So there is a great deal to be done. The field of pharmacogenomics will help overcome current limitation and optimize therapies.”

Pharmacogenetic Testing
As the field unfolds, pharmacogenetic testing (PGT) is key to its progress, said Steven Passik, PhD, vice president of clinical research and advocacy at Millennium Health, based in San Diego, and principal investigator for Millennium Research Institute. “PGT is an extraordinarily exciting area. We are looking at genetic variants and how they interact with and predict how people metabolize medicines – whether at the level of the liver or the receptor level in the brain. We are learning to determine if individuals are going to respond to medicines — both from the point of view of the likelihood they’ll get efficacy from a particular drug, as well as how likely they are (or not) to have side effects. To me this is really the essence of personalized medicine. “

With specialties in pain and addiction, Passik believes pharmacogenetics is one of the few drivers moving pain/addiction medicines forward. “While pain management for cancer has been moving steadily ahead, in certain aspects, like drug discovery and matching medication-assisted treatments to patients, addiction medicine is largely where it was 25 years ago,” he lamented.

“Several years ago there was excitement when naltrexone – an opioid antagonist — showed some efficacy in people with alcoholism stop drinking. It went into clinical use but it wasn’t a cure-all; excitement cooled. Only years later did we come to learn that there is a genetic variation in people’s opioid receptors that predicts who is likely to respond to naltrexone. Some of the earlier dying down of enthusiasm might have been mitigated if the right people had been matched to that treatment in the first place; the important positive results of its use would not have been diluted.”

This recognition of the varying usefulness of one drug to different people depending on their varied genetic makeup is, according to Passik, “. one of the most exciting developments in the addiction space in regards to pharmacogenetics.”

It is a sentiment shared by Sadee who told AAPS, “The number one landmark achievement [in the field] is that we now fully recognize that genetic factors play an important role in drug response. Over the past decades we have been mapping many of the human genetic variations that affect disease and its treatments, and there are already several examples where determining the genetic makeup of the patients is part of therapy . So while this field is ever evolving and has a great deal of growth potential, we’ve identified the importance of genetics in drug therapy. We can now implement that knowledge into providing proper treatment to patients.”

Impacting Outcomes and Costs
Passik further noted that not only will pharmacogenetics help clinicians guide patients to the best treatments and outcomes, but it will also take a strong hand at helping to contain the runaway train of healthcare costs.

“While the costs of doing tests must always be considered, along with reimbursement issues, one of the things that will develop as more data amasses is the emergence of potential cost savings associated with more quickly zeroing in on a treatment that is suited to the individual,” said Passik.

He illustrated his point via the example of opioid response, which can be idiosyncratic and dictate a great deal of trial and error. “In healthcare we’ve necessarily have had to do expensive serial drug trials, which are not particularly safe because every once in a while you have a person for whom a drug is particularly mismatched or interacts badly with their other meds, and you have the growing problem of opioid overdoses, etc. Could pharmacogenetic-guided drug selection have cut down some of that trial and error and some of that cost, and made it safer to have opioid trials? The answer is – obviously – yes.”

Passik explained that Millennium Health uses a simple inside-the-cheek swab to collect DNA for pharmacogenetic testing. “We’ve experimented with different collection devices, and use one now that doesn’t require a lot of saliva . which can be an important factor for some people who experience dry mouth as a side effect of a disease state or medications. We initially had a four-gene offering, but have subsequently added a number of other genes as we start to see their promise. [Millennium Health announced Feb. 3 that it has added three new genes to its menu that helps clinicians prescribe the right medication for patients requiring mental health treatments. Millennium PGT now looks at 14 genes and how those genes affect 41 medications including Prozac.] In our case, we have groups of scientists who review the medical literature. There has to be enough human – not just animal, not just test tube – data that suggest the value of a new gene test before we consider adding it to our offerings. “

One of the newest “rising star” assays, where pharmacogenetics has been a driver, is impacting the field of psychiatry. “This is really interesting and exciting,” said Passik. “Psychiatry meds often take a long time to work. You have patients who are depressed, feeling hopeless and possibly suicidal. They often are not adherent medicine-takers. Do we really want to waste three or four months to see if a drug will even work? Of course not. So not surprisingly, some of the psychiatric use of PGT is far ahead of other areas in medicine.”

Complexity Ahead
As the FDA already delivers mandates for pharmacogenetic testing in the labeling of many drugs, the field can only expand. Various labs are adopting additional therapeutic areas, such as testing around pain, addiction, cardiovascular therapy, and more. “And they are finding it best to test a combination of genes,” said Passik. “This is highly complex and will invoke multiple genes.”

Sadee, too, offered an important perspective to pharmacogenetic testing when he noted to AAPS, “In looking into genomics and understanding the complexity of what we are dealing with, we have to understand that progress will be incremental. There will be many breakthroughs that at first may look like giant steps in therapy, but invariably, we might find the issue to be much more complex than originally thought. It will be a long struggle until the research will have real impact on health in this country and around the world. The more I study pharmacogenomics, the more I realize this is a very difficult task that lies ahead. Even if we find solutions that can significantly improve health care, these will need to fit into a healthcare system that is, as of yet, unprepared to incorporate genetic information. Education of health care providers and patients is going to be critical as well.”

Passik concluded that the adoption and expansion of pharmacogenetic testing is ultimately all about excellence in patient care – helping people to get well in as short a time as possible, with as little waste (both to patients and the healthcare system) in that process as possible.

“I have read that we spend $320 billion on prescription meds in the U.S. per year, and another $300 billion trying to fix the problems of poor adherence to those medications,” said Passik. “Why does this happen? Patients get medicines, take them, and if they don’t work or if they cause intolerable side effects, patients shove them into a drawer. They become non-compliant, they don’t go back to the doctor, and their health deteriorates, which in turn runs up other healthcare costs,” enumerated Passik. “One of the key ways to solve that conundrum is to utilize more personalized medicine and get to the therapies that will work faster. “

In his January 2015 State of the Union address, President Barack Obama called for precision medicine and underscored the need for “the right medicine at the right time.” Pharmacogenetic testing’s time has come; it is a vital part of that precision and personalization that is shaping the growing impact of medicine.

Valerie Neff Newitt is on staff at ADVANCE. Contact: vnewitt@advanceweb.com.

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