PGx is an abbreviation for Pharmacogenomics or Pharmacogenetics. Although those “in the know”, in the large drug companies, now just call it “PG”.
Today was the first day of the ‘5th Workshop: Regulatory Decision Making’, sponsored by the FDA and the DIA (Drug Information Association), held in Rockville, MD. The crowd was about 300 attendees, including a large representation from both “Big Pharma” and the FDA. The estimates for investment by the 12 or so companies that make up the “FDA-Industry Working Group” is more than $12 billion worldwide, for the development of drugs that reflect genetic variation in individuals related to drug response. Sessions were focused on new rules for labeling drugs that require gene testing, and the global need for “Big Pharma” to obtain as many personal genomic samples as possible by empowering regulatory bodies in the U.S. and other countries.
Pharmacogenomics-based personalized medicines offers new marketing opportunities:
- Genotyping may be used for rescuing “dead drugs” that have failed clinical trials because of lack of efficacy and toxicity problems. New indications can be explored in defined populations groups where the drug use is safe and effective.
- Pharmacogenomics may be applied to expand markets for approved drugs with generally restricted use because of limited efficacy and toxicity in some patients. By defining the genotypic characteristics, patients who are non-responders and those liable to adverse reactions, can be excluded.
- Repositioning of a drug through pharmacogenomics can extend the patent life of a drug. A drug with redefined new indications for a particular group of patients would start a new patent life.
- Upper figures for efficacy of current drugs for most diseases are less than 100% – Improvement by developing personalized drugs is an opportunity for expanding the market, including the reduction of side effects that are probably the result of individual genetic variation.
However, I had the temerity to ask the audience – What about the physician? How are they going to learn about this new domain of PGx and genomics in a broader context? Apparently no one at the FDA is worried about whether physicians are educated in this new domain – they may be relying on MEDCO and CVS pharmacies to intervene and control the process. I doubt this will be a successful strategy.
It is of interest to note that the HHS Secretary’s Advisory Committee on Genes, Health and Society recommends “the use of the Electronic Health Record” for collection, storage, tracking and centralizing both personal genomic and PGx data. We shall see…more to follow…
jbormel says
Gerry,
At AMIA in November of 2009, Harry Enchin from Oregon Health and Science University addressed our PG topic in a presentation “Is Patient Safety the Low Hanging Fruit of Personalized Medicine?”
He started out by effectively making the case “Lack of drug efficacy and adverse drug reactions (ADRs) drive the need for safety pharmacogenetics.”
In the course of providing evidence that Physician habits are hard to change, he offered “Clinicians prefer phenotyping TPMT (thiopurine methyl transferase) levels to genotyping.”
He suggested that there are structural challenges beyond educational needs: “Lack of efficacy and entrenched pharma/physician business models dominate several barriers to PGx.”
Are you proposing a specific policy regarding detailing physicians on PG?
Gerry Higgins says
jbormel-
I could write a book chapter about this, but I will try and keep it short. Safety PGx is the big concern, and warfarin is the poster child. You are right about physicians having entrenched habits, which is why the FDA recently (1/22/10) changed the drug label for warfarin from ‘Required’ gene testing prior to dosing to ‘Recommended’ gene testing – there was too much pushback from the ACP and others. However, the scientific evidence, including that from clinical trials is so large now (22,000 PGx medical/scientific publications in the last 2 years, 20% of these since 12/09!), that I am proposing that the practice of medicine will have to change. The evidence is just too great – yes, there may be rare variants that contribute to common, complex disease, but there are lots of data on common variants that predispose an individual to have 5-100 times of having an ADR to certain drugs.
The Big Pharma have already bought into the new business model, they stand to benefit greatly from co-marketing PGx biomarker tests along with drugs, as well as identifying vulnerable subpopulations to mitigate exposure early on in the drug pipeline process.
Since being a member of the ONC committee, we are going to propose policy changes that will require doctors to use PGx, in the context of a Clinical Decision Support System, when available.
We can’t wait for another generation of physicians- a recent large survey showed there was no significant difference between physicians in their 50’s and those who just graduated medical school in their understanding of the “new’ genomics, including simple definitions like “disease allele” and “penetrance” – they were equally ill-informed.
jbormel says
Gerry,
Can you recommend a primer on PGx?
Would using a PGx-based prescribing framework likely put an end to the commercially propagated pseudo-science between brand and generic drugs? Does it have that potential?
-Joe
Gerry Higgins says
Jbormel-
I can send you a long primer on PGx, if you can contact me at [email protected].
And the answer to your second question is no, in fact, the opposite is true.