How FDA is preparing for wave of change to personalized medicine?

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The cost of DNA sequencing is dropping continuously. In very future, majority of the population will have access to their genetic background and they will be able to take it their doctor and will expect to receive personalized treatment rather than a drug that has worked for millions of people but not guaranteed to work for them. Pharmaceutical industry will eventually have to change their business model and transition to personalized medicine. I am wondering how this impacts the regulatory affairs in pharmaceutical industry. How the FDA is preparing itself and evolving to address this trend of change to personalized medicine?

Vijay Kumar
82 months ago

29 answers

4

Dear Vijay,
I think that FDA will have time to decide in early stages of personalizing medicine, because the main thing that needs adjustment is the quantity of drug a person should take to be effective.
If some existing drug is not effective, the second approach should be changing the drug, combining two drugs or using enhancers.
In the future, and taking on account the evolution of CRISP-like methods and gene therapies, the framework should change to include this as a new genome driven medicine.
Regards,
Juan Pablo Allocati
jallocati@hotmail.com

Juan Pablo Allocati
82 months ago
Say what? - Dr. David E. 63 months ago
4

The "one-size-fits-all medicines" description has been used by Mr. Carotenuto as a criticism. There is no need to be so negative; in fact, one-fits-all is perfectly fine for example for antibiotics, as long as physicians are willing to determine what particular organism / bacteria has infected the particular patient.
Somewhat incorrectly termed "personalized medicine" - a better term is "precision medicine" approach does something similar, by first determining the actual cause of disease and then applying appropriate therapy. It is not intended to be tailored to individual patients but simply to a subset of patients that possess the appropriate genetic / other relevant biological background.

Karel Petrak
81 months ago
Dear Kerel, I perfectly agree with your statement. I didn't want to be critic, I was arguing about that the new era of personalized medicine is just started. My previuos inputs showed which is the state of the art. I am far from critical, I am working in this field and I believe that the results of these approaches for both personalized medicine and precision medicine will soon be quite practical. - Pietro 81 months ago
OMG - Dr. David E. 63 months ago
3

First of all we have to define the needs of personalized medicine in specific and only then it can be applied efficiantly.second, it should include building a personal profile of ones needs as for the all taken drugs inpot and address also the interaction infuance between all the drugs input because now it is very much can cause more harm then help if not taking this issue into consideration . - ORIT

ORIT BOSSI (PhD)
82 months ago
More walking - less food - reduce moral hazards = health and wealth - Dr. David E. 63 months ago
3

The Personalized Medicine is just an ongoing practice fro FDA. I'm describing a briefly report to reply to the main question.
In 2016, for the third year in a row, personalized medicines accounted for more than 20 percent of all new
molecular entities (NMEs) approved by the U.S. Food and Drug Administration (FDA). FDA’s Center for Drug
Evaluation and Research (CDER) approved 22 NMEs, new drugs, agents or
therapeutic biologics, in 2016. Of the 22, the Personalized Medicine Coalition (PMC) classified six of them — more
than 25 percent — as personalized medicines, continuing a trend that PMC first documented in 2014 when it pointed out that nine of 41 NMEs approved that year are personalized medicines. The analysis underlines that nearly one of every four drugs the agency approved from 2014 to 2016 is a personalized medicine. That ratio is a sharp increase from 2005, when personalized medicines accounted for just 5 percent of NME approvals. When evaluating NMEs, PMC categorizes personalized medicines as those therapeutic products for which the label includes reference to specific biological markers, identified by diagnostic tools, that help guide decisions and/or procedures for their use in individual patients.
Newly Approved Medicines
The six personalized medicines approved in 2016 include:

  1. Rubraca (rucaparib) for the treatment of advanced ovarian cancer. The decision to use this product
  2. is informed by the BRCA1/2 biomarker status in patients.
  3. Exondys 51 (eteplirsen) for the treatment of Duchenne muscular dystrophy. The decision to use
  4. this product is informed by the DMD mutation biomarker status in patients.
  5. Epclusa (sofosbuvir and velpatasvir) for the treatment of chronic hepatitis C infection. The decision
  6. to use this product is informed by the HCV genotype status of the viral infection in patients.
  7. Tecentriq (atezolizumab) for the treatment of advanced or metastatic urothelial cancer and
  8. metastatic non-small cell lung cancer. The decision to use this product is informed by PD-L1
  9. expression levels in the tumors of patients.
  10. Venclexta (venetoclax) for the treatment of chronic lymphocytic leukemia. The decision to use this
  11. product is informed by the chromosome 17p deletion biomarker status in patients.
  12. Zepatier (elbasvir and grazoprevir) for the treatment of chronic hepatitis C infection. The decision
  13. to use this product is informed by the HCV genotype 1 and 4 biomarker status of the viral infection
  14. in patients.
Pietro Carotenuto
81 months ago
Exhaustive - Dr. David E. 63 months ago
2

Some one from the FDA can no doubt answer this question.
Let's step back and verbalize what we anticipate the "personslized" medicine will actually look like in practice. I anticipate that the main change will be in terms of disease diagnosis, for example based on gene analysis determining what drug would be most effective for an individual patient. No drugs will specifically be made for individual patients. The current Precision Medicine Initiative does not include developing personalized precision drugs, hence the treatment will still use the existing therapies.

Karel Petrak
82 months ago
First of all we have to define the needs of personalized medicine in specific and only then it can be applied efficiantly.second, it should include building a personal profile of ones needs as for the all taken drugs inpot and address also the interaction infuance between all the drugs input because now it is very much can cause more harm then help if not taking this issue into consideration . - ORIT 82 months ago
HMMMMM! Not likely - Dr. David E. 63 months ago
2

A wave of change? Not really. Just a normal progression...

Karel Petrak
81 months ago
Agreed - Dr. David E. 63 months ago
2

I agree. Not a wave of change.

Lisa Kilawee
81 months ago
As the world making progress everything becomes personized because its the right approach in the new era, - ORIT 81 months ago
OK - Dr. David E. 63 months ago
2

The biggest cost of drug development is not in drug discovery and development (this cost being under the control of pharmaceutical companies), but in the clinical-trial phase (the cost of this is driven by clinical investigators and their institutions). Further, an average cost of drug development is high because only few percent of drugs entering development reach the market (due to failure of clinical studies to reach the desired outcomes).
It would be very useful to come up with ideas as to how to implement the "One by one, painfully, there can be quality driven improvements along with efficiencies that ultimately will trim down costs of care" approach could be applied to clinical studies...

Karel Petrak
80 months ago
There have been drugs proven successful when these are tested & used in other countries; large healthcare organizations & patients are benefiting from these drugs or implantable devices administered out of United States (also often less costly). Globally available Big Data (when possible) can help put together related sustainable regulations. - Norma H. 74 months ago
Name a few? - Dr. David E. 63 months ago
David: I have no idea. I was sarcastically quoting an earlier suggestion by another reader saying “ “One by one, painfully, there can be quality driven improvements along with efficiencies that ultimately will trim down costs of care" - Karel 63 months ago
OK - No problem. - Dr. David E. 63 months ago
2

Production facilities and technologies needs to upgrade to this level of medical needs.... Era of the targeted and personalized drugs is ongoing but big pharmas doesn't want it to arrive too fast in order to be able to use their brand new facilities for years and years...

Franck PAVAN
79 months ago
Not needed = walk more - eat less - reduce moral hazards - Dr. David E. 63 months ago
2

I see that my answer is providing a lot of comments, that's great!!! Thanks to Pietro to provide such an input in the personal medecine field. That's good to know at raise a question, how many patients are treated yearly per such specific needs? What are the manufacturers doing to meet that demand? That's the question I raised by telling that such manufacturing demand is not in line with big factories...

Franck PAVAN
78 months ago
Few - Dr. David E. 63 months ago
2

Hello Karel,
This answer is tipical from research specialist who are defenetly looking to discover molecules or treatment which aims to solve specific therapies. Once this has been done, you can't move your product to market simply because it is considered accurate, you have to comply with a bunch of regulatory items which are far from the benchtop studies in order to insure not only the accuracy of the treatment but also the safety of the product and the reproduibility of the manufacturing. Nevertheless, I will be mild in my conisderation and will let you think the way you do. Unfortunately, I have experienced many discovery which have been left at research stage because of this lack of understanding of the regulatory issues to move the product to market.

Franck PAVAN
78 months ago
WOWSA! - Dr. David E. 63 months ago
1

Reading this informative comment it occurred to me that the term "personalized medicine" is somewhat of an exageration. To some extent it matches the definition that designation as "personalized" "meets someone's individual requirements".
However, to be more exact, the "personalized" medicines in the current context simply add more definition, specification about what group of patients the drug should be used.
Every FDA-approved drug comes with a package insert that clearly describes its INDICATIONS AND USAGE. Adding to this information more specific description relating to the mode of drug action does not make it "personalized". It simply narrows the size of the population for which the drug may be effective...

Karel Petrak
81 months ago
Agreed - Dr. David E. 63 months ago
1

Yes, the new era is just started:
THE PHARMACEUTICAL industry makes billions of dollars a year selling one-size-fits-all medicines. But now the race is on to come up with tailor-made drugs that will treat people based on their individual genetic makeup.
Drug companies hope to create a map of genetic landmarks that will become a potent new tool for uncovering the minute inborn differences that make some individuals particularly susceptible to certain diseases. With that knowledge, the drug makers hope to develop safer, more potent drugs that can more precisely target the variety of biological quirks that underlie each major disease. Their goal: a cornucopia of personalized medicines that will produce huge profits into the next century.

Pietro Carotenuto
81 months ago
NOPE: Not needed = walk more - eat less - reduce moral hazards - Dr. David E. 63 months ago
1

Let me make few points.
Cost of DNA analysis is of little significance in the current care for patients. 1. physician is unlikely to know what the heck the analysis means in relation to the patients condition, and 2. if he does, appropriate specific, "precision" medicines are not yet available.
Further, personalized medicines are unlikely ever to be made to fit individual patients. As it is now, medicines are developed for groups of patients with the same disease and a similar biological / genetic / etc. background.
Two government programs are currently under way - Precision Medicine Initiative to generate new information about the nature / mechanisms / of diseases and life-style effects on disease, and Accelerating Medicines Partnership to generate knew knowledge so that clinical srudies could be designed to fail less often. Neither of these projects aims to develop new drugs; that task is being left to pharmaceutical industry.
Easing regulatory burden will not cut it. We first need more knowledge about diseases and consequently better drugs. Making regulations easier is likely to achieve only one thing - more bad drugs will be made faster!

Karel Petrak
80 months ago
DNA analysis is making a big significance in the current cancer treatment care for patients. Genomic testing is being performed on a patients T-cells and cancer cells. The T-calls and some HIV cells DNA are being programmed to target and kill only other cancer cells while ignoring the patients healthy cells. - David 74 months ago
Well said and writen; thanks - Dr. David E. 63 months ago
1

I'm reporting below a briefly summary of a paper on Nature of April 2015 higliting the "great promise" of the Precision Medicine.
Every day, millions of people are taking medications that will not help them. The top ten highest-grossing drugs in the United States help between 1 in 25 and 1 in 4 of the people who take them (see 'Imprecision medicine'). For some drugs, such as statins — routinely used to lower cholesterol — as few as 1 in 50 may benefit1. There are even drugs that are harmful to certain ethnic groups because of the bias towards white Western participants in classical clinical trials2.
Recognition that physicians need to take individual variability into account is driving huge interest in 'precision' medicine. In January, US President Barack Obama announced a US$215-million national Precision Medicine Initiative. This includes, among other things, the establishment of a national database of the genetic and other data of one million people in the United States. Classical clinical trials harvest a handful of measurements from thousands of people. Precision medicine requires different ways of testing interventions. Researchers need to probe the myriad factors — genetic and environmental, among others — that shape a person's response to a particular treatment.
Studies that focus on a single person — known as N-of-1 trials — will be a crucial part of the mix. Physicians have long done these in an ad hoc way. For instance, a doctor may prescribe one drug for hypertension and monitor its effect on a person's blood pressure before trying a different one. But few clinicians or researchers have formalized this approach into well-designed trials — usually just a handful of measurements are taken, and only during treatment.
If enough data are collected over a sufficiently long time, and appropriate control interventions are used, the trial participant can be confidently identified as a responder or non-responder to a treatment. Aggregated results of many N-of-1 trials (all carried out in the same way) will offer information about how to better treat subsets of the population or even the population at large.
Formalizing and scaling up the N-of-1 approach means solving various practical problems. These include exploiting the diversity of health-monitoring devices, developing new ones and identifying appropriate disease biomarkers, such as tumour DNA circulating in the bloodstream. It will also require a cultural shift on many levels — in regulatory agencies, in pharmaceutical companies and, most of all, in the clinic.

Pietro Carotenuto
78 months ago
“Aggregated results of many N-of-1 trials (all carried out in the same way) will offer information about how to better treat subsets of the population or even the population at large.” Is this not the same as most of standard trials? Results for individual patients, pooled, averaged, interpreted? - Karel 78 months ago
OK - Dr. David E. 63 months ago
1

FRANK:
You either did not read my text correctly, or you did not understand it. I WAS CLEARLY TALKING ABOUT APPROVED DRUGS, for which all you talk about (safety, tox, manufacturing validation, etc. and CLINICAL STUDIES have been done to the FDA satisfaction. I am not talking about an R&D but about the whole drug development and approval process. PM - precision medicine - needs to be precise. Such task will include manufacturing but will not be solved by manufacturing. Pharma industry has a long way to go ...
Karel

Karel Petrak
78 months ago
So Karel, by the way we are on the same page then. - Franck 78 months ago
WOWSA! - Dr. David E. 63 months ago
1

Courtland: not really a disagreement, but we come to this topic from a different perspective. On another location of Convetit I paralleled personalized medicine to other consumer product, clothing. One has three basic choices - getting “one size fits all” version, “off the peg”, or “made to measure”. Currently, medicines are closest to the “one size fits all” version, with some broad groups (men, women; adults, children) adjustments of doses and formulations. I imagine that Big Pharma could develop a “personalized versions” for relatively sizable groups such defined on the basis of features of a given disease (e. g., such as DNA defects). For a personalized medicine of the “precision medicine” type, diseases will need to be defined for individuals in terms of exact mechanism(s) of disease including specific structural targets through which a given disease could be treated (one can parallel this to the clothing situation and call it a “made-to-measure” medicine). Pharma still needs to wait for our basic science of disease to reach such a level of sophistication.
Karel

Karel Petrak
74 months ago
CHEESE - Dr. David E. 63 months ago
0

Given the politics in Wash DC these days, its confusing with mixed signals as to trend or speed of change. However, the direction for change and easing regulatory burdens is now becoming much clearer. FDA speeding up drug approvals, CMS reducing administrative burdens, and some Executive Orders to-date by Trump clearly support allowing progress to be made while embracing new technologies in a safe manner.

Randy Vogenberg, PhD
80 months ago
Agree - Dr. David E. 63 months ago
0

Good point about continuing bad drugs, however, there are costs associated with everything that is done in research, development, production, marketing and sales. One by one, painfully, there can be quality driven improvements along with efficiencies that ultimately will trim down costs of care.
Perhaps the biggest savings actually comes in contracting with 3rd parties and middleman during marketing phase of the drug.

Randy Vogenberg, PhD
80 months ago
Avoid middle men and PBAs to the extent possible. - Dr. David E. 63 months ago
0

Franck makes some great points on ROI and investment in personalized medicine. Lots of unanswered questions that are likely to continue through 2018-2019 due to lack of meaningful Congressional action.

Randy Vogenberg, PhD
79 months ago
YEP - Dr. David E. 63 months ago
0

It has been amazing to see the progress being made along with the effort to continue improvements that make FDA more efficient while acheiving its mandated mission for safety and efficacy.

Randy Vogenberg, PhD
79 months ago
Maybe - Dr. David E. 63 months ago
0

Precision or personalized medicine is washing ashore into the USA marketplace as the confluence of market timing builds more waves that will result in more product entrants at an increasingly faster pace.

Randy Vogenberg, PhD
78 months ago
More hype than help; thus far - Dr. David E. 63 months ago
0

Manufacturers aren't clear in describing what they are doing to meet the demand for personalized medicine. Such new technology demand clearly is not in line with traditional manufacturing and most likely could lead to unique collaborations with hospitals or clinics for joint "manufacturing" of individualized therapies.

Randy Vogenberg, PhD
78 months ago
Not any time soon. One third of hospitals are fiscally deficient, and growing - Dr. David E. 63 months ago
0

I definetly consider that there is a space for dedicated CDMOs which adapt the manufacturing equipment and technology to the needs in order to address such specific demand. Disposable systems could help in designing such tools.

Franck PAVAN
78 months ago
0

The issue of personalized medicine / precision medicine (PM) is not to "...adapt the manufacturing equipment and technology to the needs in order to address such specific demand." In order for PM to work, by the time the general population of patients will have access to information on their genetic background, clinical studies for drug approval will need to be performed with subjects for which genetic backround is fully documented, and drugs will need to be approved only for populations of patients for which the drug has therapeutic efficacy.
All this of course depends on the validity of assumption that genetic background is the only factor that determines drug efficacy. This assumption is unlikely to be true in all cases...

Karel Petrak
78 months ago
EXPENSIVE - Dr. David E. 63 months ago
0

2017 final approval numbers by FDA are astounding when compared to last 3 years. Efficiency changes and focus on speeding pipeline activity through phases begins to set stage for precision/personalized medicine strategy in the market.

Randy Vogenberg, PhD
75 months ago
So true, Randy. I also noted the numbers! I am surprised that this board does not consider one of the biggest drivers of precision medicine: IT technology to make the INTERPRETATION of one's genome accessible to all treating phsyicians. As an example, Syapse in US is tackling presciion medicine for cancer. My company, Pillcheck.ca, is doing a similar work for non-cancer treatments. - Veronika 74 months ago
IT is a given, perhaps it can be beneficial to brainstorm potential IT architectures in support of telemedicine. - Norma H. 74 months ago
PillPack Reviews - Is it a Scam or Legit? - 2/5 stars: https://www.highya.com/pillpack-reviews - Dr. David E. 63 months ago
0

Interesting discussion. No one has mentioned one of the biggest opportunities for personalized medicine- compounding pharmacies. I see FDA noting this opportunity several years ago. Industry and FDA must work together to achieve the greatest mutual benefit. I see the FDA reaching out more than ever.

COURTLAND IMEL
74 months ago
Not true. I clearly mentioned it in my earlier email, also pointing out that compliance with standard and safe procedures are sometime not adhered to at compounding pharmacies. That resulted in some cases in serious safety issues, with the FDA acting accordingly. - Karel 74 months ago
Karel, We are in disagreement. Yes, FDA has taken action against a number of firms, the original dirty thirty, and more have been added, cited, and posted. My point is that big Pharma is getting into compounding pharmacy. We don't mention those firms that do it correctly. I see more and more firms turn on their lights. It's the next major growth area. Like you, I was surprised to hear this - COURTLAND 74 months ago
OK - Dr. David E. 63 months ago
0

The topic of personalized medicine or precision medicine should not just be focused on the civilian population but also include the US military both active duty, Reserves and separated/retired wartime and non-wartime veterans.

With this said and repeated many times over, hospitals, emergency workers, the CDC, US military all need to continually train and treat not only the most commonly seen diseases/illnesses but train/treat for the lesser seen diseases also to include biological, chemical, radiation, etc. The military has used Agent Orange and other chemicals during the Vietnam War. These soldiers are getting more health problems the older they get due to their war time and non war time military service. Same for the Gulf War veterans with the "Gulf War Illnesses/syndrome". Many research studies have been done by the VA =Veterans Administration, Universities and other institutions to figure out what agents were used during their military war service and what is causing an increase in their health problems. These health problems often times occur many long years after the service member left the military. Civilian healthcare workers need to have additional training to be able to better diagnose, treat and hopefully cure these aging veterans. There conditions could/can also be affecting their family members (kids) when they try to reproduce. So many of the health conditions could/can have a multi-generational effect. Very few cures for their conditions.   

David Barckhoff-Sag-Aftra/Producer, Director
74 months ago
Forget the VA; sorry - Dr. David E. 63 months ago
0

DNA analysis is making a big significance in the current cancer treatment care for patients. Genomic testing is being performed on a patients T-cells and cancer cells. The T-cells and some HIV cells DNA are being reprogrammed to target and kill only other cancer cells while ignoring the patients healthy cells. This is a great benefit to the patient. Whereas traditional chemo treatments kill both cancer and healthy cells. Some chemotherapies don't work at all on killing a patient's cancer cells, so another agent is used until the correct medication works. Sometimes chemo does not work, then radiation and surgery might be the answer or a combination of treatments need to be tried until it works to kill the cancer. This unnecessarily burdens a patients already diminishing health. A for personalized medication would be more beneficial for the patients treatment. DNA is already being used for genealogy research and for predicting the likelihood of a person to getting specific disease or condition later in life, so why not use it to manufacture better medicines that will help people rather than a "one size fits all" approach? or is it better to say, "One size doesn't fit all" when it comes to medications and treatments.

David Barckhoff-Sag-Aftra/Producer, Director
74 months ago
"One size doesn't fit all" when it comes to medications and treatments. For socialized medicine or the masses it sure does. - Dr. David E. 63 months ago

Have some input?