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A Summary of the USTP’s FDA Reform Panel – Article by Dan Elton

A Summary of the USTP’s FDA Reform Panel – Article by Dan Elton

Daniel C. Elton, Ph.D.


The U.S. Transhumanist Party livestreams special Enlightenment Salon events every Sunday at 4 p.m. on YouTube. Two weeks ago, on April 4. 2021, the USTP organized a special Enlightenment Salon panel event on FDA reform. In addition to myself, the following people participated on the panel, which was moderated by USTP Chairman Gennady Stolyarov II:

  • Prof. Alex Tabarrok, Bartley J. Madden Chair in Economics, George Mason University
  • Dr. Max More, President Emeritus, Alcor Life Extension Foundation
  • Jim O’Neill, CEO, SENS Research Foundation
  • Dr. Edward Hudgins, Founder, Human Achievement Alliance
  • Prof. Garett Jones, Mercatus Center, George Mason University
  • Willy Chertman, Medical Student and Blogger

The entire panel was probably the most information-dense event the USTP has done. I kicked things off by giving a short presentation, which I managed to blaze through in 15 minutes. (The slides can be viewed here.) The presentation set the stage for a very informative and productive discussion.

My only regret was that we didn’t have any women on the panel. However, during the course of researching my presentation, I found out about the work of Dr. Mary J. Ruwart. Dr. Ruwart estimated the number of people who die every year from FDA delays to be around 150,000 per year in her book Death by RegulationSo, I am happy to announce that Sunday, April 25th, from 4 – 6 p.m. Eastern Time, 1-3 p.m. Pacific Time, the USTP will be doing a special Virtual Enlightenment Salon with her.

Here is the recording of the FDA reform event. At 00:05:00 my presentation kicks off:

I’ve written a summary of the major points each of the panelists (and two others) made during approximately the first hour of the session. These are heavily paraphrased. (Instead of providing direct quotes, I shortened what was said in most cases while maintaining the core meaning of what was communicated.) I have put my own comments in italics.

Prof. Alex Tabarrok:

  • The FDA can approve a bad drug (Type I) or fail to approve a good drug (Type II). If they approve a bad drug, people who were affected will go on Oprah, and there will be huge backlash. If they don’t approve a good drug, there is no backlash. The invisible graveyard is a statistical reality, but it’s hard to see. This can be seen easily by asking people to name a time when the FDA approved a bad drug (or a drug with unexpected side effects). Lots of people can think of something. Many point to Thalidomide, which is actually a drug that was approved in Europe and caused birth defects. Thalidomide, incidentally, has many important applications but was not approved by the FDA until 1998.
  • When you have a Type I error, you learn something — we learn about the harms of a drug, and we change our behavior. With a Type II error we never learn anything. We can’t see the consequences of a failure to approve, and even worse, we can’t see the many drugs that never even made it to FDA-mandated trials in the first place because they were deemed too risky to justify the cost.
  • Reciprocity is a sensible reform that is one of the most feasible.
  • The FDA likes to think they are the “gold standard” for drug approval. Yet, people in other countries don’t worry about whether drugs are FDA-approved. For food safety we already have reciprocity with Canada.
  • The FDA has been working for 40 years on new standards for approving sunscreens. So Europeans have much more advanced sunscreen than the US.
  • If aspirin were invented today, it probably wouldn’t be approved.
  • One thing U.S. policymakers have done already, which is probably the smartest thing they have done in a while, is PEDUFA (Prescription Drug User Fee Act). The drug developers pay an extra tax as long as approvals are sped up. The FDA was happy because they got to expand their bureaucracy, and drug companies were happy because they could get to market faster.
  • In the EU the EMA “farms out” reviews to private companies. (So the EMA is more like “an approver of approvers”). Private companies can do a good job – for instance, look at Underwriters Laboratories in the realm of electrical devices. (If you look at many electrical devices, you may see a “UL” seal.) Many major companies like Amazon won’t carry devices unless they are UL-approved.
  • There is no formal process whereby where if a disease is more deadly, then the standards should be lowered to speed approvals. For instance, for pancreatic cancer, which often kills within 6 months, the standards should be lower (and more risk should be tolerated), since patients have less to lose. For something like acne treatment, the standards can be much higher. The FDA recognizes this to some extent in practice, but it’s totally informal – technically it’s not supposed to happen. However they could do this formally and adjust the required statistical significance levels. They could use Bayesian statistical techniques as well.
  • There’s no route to approve a drug for anti-aging. If a company wants to do R&D on anti-aging therapeutics, there is not a clear route for approval.

Dr. Max More:

  • We should keep in mind full abolition of the agency as a long-term goal. [My response: I am against full abolition, but I agree with this. Everyone should at least consider abolition, and if they are against it, explain in some detail why the government needs to be involved versus using private-sector companies and tort law. Going back to first principles regarding the role of government is healthy, especially in places like Washington, D.C., where government institutions are taken for granted and not questioned as much as they could be.]
  • We should keep in mind Milton Friedman’s statement that expecting the FDA to behave differently than it does is like expecting a cat to bark (Note: He said this in a 1973 Newsweek column.) We can’t just say, “We want the FDA to do X”; we have to make sure incentives are in place so people actually do the things we want. Legal mandates can help, but it’s easy for people to skirt around them if the proper incentives don’t exist.
  • We are facing an enormous cultural barrier when it comes to reforming the FDA and CDC. We don’t have a proactionary culture anymore; we have a very fear-based culture, and a simple solution to it does not exist. However, we have a good opportunity right now just like the AIDS activists had a good opportunity in the 1980s.
  • The proactionary principle is a “grab-bag” of tools based on a certain value perspective which basically says that progress is fundamentally good. We aren’t omniscient, so we have to learn by doing. As Alex Tabarrok said, you can’t really learn things without making mistakes. It’s impossible to make progress, like some rationalists believed, by just sitting in chairs and thinking carefully. We have to become empirical. You can “look before leaping”, but you also have “look while leaping” and adjust how you land, to use a crude metaphor.
  • Cost-benefit analysis is a basic approach that is used in many organizations but doesn’t seem to be used as much in government agencies. It shouldn’t be controversial. Mandating cost-benefit analyses would be a step towards using ideas from the proactionary principle.
  • We should institutionalize the Devil’s Advocate procedure and institutionalize respectful disagreement. Instead of having the most powerful person in the room getting what they want railroaded through, we should require debate and motivate decision makers to ponder both sides. Other approaches could help, such as reference class forecasting, structured argumentation techniques, auditing procedures, and auditing review panels.
  • Reciprocity seems like a no-brainer that is relatively easy to achieve, and would greatly reduce costs.
  • Besides getting out these great ideas, we need to figure out how to get people to follow those ideas. Laws can help, but people can choose to not follow them. How do we put “bite” into laws? I think an annual audit on the FDA’s decision making would be a good idea. Importantly, the auditor’s report should be made public. The auditors should come from a variety of institutions, for instance a variety of think tanks from different sides of the political spectrum.

Gennady Stolyarov II:

  • The USTP agrees that abolishing the FDA should not be out of the question. In our Platform, Section CXVIII states:

Section CXVIII [Adopted by a vote of the members during March 25-28, 2020]: Given the extreme delays, bottlenecks, and expenses created by the mandatory approval processes on the Food and Drug Administration (FDA), the United States Transhumanist Party supports abolishing the FDA and replacing it with a Radical Life Extension Administration (RLEA), whose mandate would be to prioritize the rapid development of potential disease cures, treatments, and vaccines – including any possible cures or vaccines for COVID-19, as well as treatments to mitigate and reverse the disease of biological aging, the major risk factor for COVID-19. The RLEA would allow the marketing and collection of patient data on any potential cure, treatment, or vaccine which has passed affordable safety testing at a reasonably acceptable threshold.

Jim O’Neil:

  • I’ve had the pleasure of working with the FDA quite a bit, and in my experience most of the people there are very smart, and they actually believe in approving things, contrary to what it may look like from the outside.
  • The problem is that incentives matter, and the FDA is a central point of failure.
  • When someone has a severe side effect from a drug, the FDA Commissioner gets hauled in front of several Congressional Committees and is interrogated. When someone dies because something wasn’t approved, there’s total silence in Washington. We should blame Congress, not the FDA, for that incentive being in place.
  • Individuals respond to the institutional incentives, but they also have personal incentives. A lot of people want to be the next whistle-blower who finds the next thalidomide and calls a halt to it. Both of these are pretty severe and would affect even the most principled person in ways they couldn’t even detect.
  • I disagree with Alex that “FDA not recognizing aging as a disease is a major problem.” In order for the FDA to reasonably measure success of any therapy, there must be metrics and biomarkers. It’s not the FDA’s job to do all the scientific work to develop biomarkers for aging. That’s the job of the science community and the NIH to some extent. There are epigenetic clocks, but we need a lot more work on those. Those clocks can then be run through the FDA’s biomarker approval program.
  • The second thing I disagree with is Dan’s idea of making the FDA independent from HHS. I think that would make things worse.
  • My favorite approval ideas fall under the category of “progressive approval” or what Dan calls “tiered approval”. Contrary to what the FDA often thinks, doctors and patients are capable of processing information and making risk-benefit calculations using their knowledge about the specific situation they are in. The more information provided and the more transparency, the better. The FDA should focus back on their original mission of safety and purity. I absolutely support repealing the 1962 Kefauver-Harris Amendments.

Prof. Garett Jones:

  • I come at this as an macroeconomist. I think we can learn from what economists have learned about central banks around the world. The FDA should be as independent of congress and the president as central banks are or as judges are.
  • The Federal Reserve is a panel. That’s how we run the SEC, the FEC, the Federal Reserve, and the Supreme Court. There seems to be some magic to having a panel — it’s probably giving us a bit of the Law of Large Numbers in decision-making.
  • Another aspect of these panels is they have long terms. They are probably going to be serving under a few different Presidents. As I say in my book 10% Less Democracy, “short terms make short-term thinking”. Political independence can lead to decision-making independence, and we have evidence that’s a good thing.
  • Discussions in institutional reform have “high marginal product” right now, as an economist would say. Congress moves slowly, but Congresspersons tend to look for big opportunities for reform a couple years after a crisis. The Federal Reserve was established in 1913 but was born out of the Panic of 1907. Six years was how long it took between a huge financial crisis and Congress getting around to making some reforms. We saw something similar after the global financial crisis – it took about 2-3 years. The ideas that people are discussing now will be part of the information ecology of the next few years in Washington, D.C.
  • These ideas of long terms, independence, and panels are a good path for decision making. I am an unreformed Tabarrokian, so I agree with everything Alex Tabarrok has written about FDA reform (chuckle). What I want to push here is institutional reforms that seem to work in a wide variety of settings. A little more financial and legal independence will lead to a situation where Congress is less of a source of fear for FDA officials.
  • A lot of people on social media have told me that the President is in charge of the FDA. These people have never actually talked to anyone who worked on Capitol Hill — agencies live in fear of their Congressional overlords. They live in fear of the Senate Majority Leader and the Speaker of the House, who have power over their budgets. They also know that if they make a mistake, they can be hauled up before Congress and fired ignominiously.
  • There is a risk that a more independent agency may misuse its freedom. However, in practice, if we look at the data, independent agencies with long terms have high benefits and low costs.
  • It’s fun to complain about the FDA, but it’s wise to complain about Congress.

Dr. Ed Hudgins

  • We’ve been talking about how FDA regulators are always in fear of Congress. What I want to see are FDA regulators in fear of patients who want to get access to medications at less cost and quicker.
  • One of the most egregious examples of defining efficacy was when the FDA decided that 23andme could not offer advice on whether someone was prone to breast cancer. Essentially they thought that women were too stupid to understand the information and would rush out to get a double mastectomy without getting a second opinion.
  • Another example is in 1989-1990 when they wanted to classify a urine sample cup as a “class A medical device”, in the same category as a heart valve.
  • In April 2019, the FDA stated that it wants to regulate artificial intelligence as a medical device.
  • There are many consultants now, whose entire job is to help companies get through the FDA bureaucracy. So there’s a whole industry now just to help people get through the FDA — and that’s part of the problem now, too.
  • The “Free to Choose Medicine” idea should be at the top. Something like this was created around 1992 during AIDS crisis. Congress stepped in and put pressure on the FDA to do something. What they did was create a parallel track where sufferers could access a particular medication for AIDS during the three years it was being tested. 12,000 people took advantage of that, so there are 12,000 people who are not in the invisible graveyard as a result.
  • The idea of a parallel track has been put forward by Bart Madden. Data from people on that track would be put into a public real-world database.
  • There are alternatives to randomized controlled trials (RCTs). If observational data is put into a public database, then doctors can look at that data and make informed recommendations. Drugs would be able to fail quicker, too.
  • In the case of AIDS, it was patient groups that besieged the FDA’s buildings. In light of COVID-19, and people seeing that the system isn’t working for them, we have an opportunity now to push for change.
  • There’s momentum for FDA reform building off of the right-to-try legislation that has been passed in many states. In Texas and North Carolina there are strong pushes to broaden right-to-try to people like patients with Alzheimer’s Disease.

Willy Chertman

  • The AIDS-FDA story is a little more nuanced than was described by Ed Hudgins and Max More. We all know about the militant groups like ACT-UP which pressured the FDA in the 1980s. However in the mid-1990s there developed a few counter-movements against that. One group was called Treatment Action Group, and they pressured the FDA to move slower because they felt the FDA was approving HIV/AIDS treatments that didn’t actually have much benefit.
  • A good book is Malignant by Vinay Prasad. It documents how, over the last twenty years or so, the FDA has lowered the standards for many cancer drugs. They often are approving drugs based on surrogate endpoints and biomarkers, and then the drugs don’t go through follow-up studies to show if they have actual clinical benefit. So there has been a natural experiment where we tried to lower the standards for cancer drugs, and it doesn’t seem to have worked very well. Of course, I’m not an economist, so there might be a way of adding up the costs and benefits where the marginal benefits have outweighed the costs.
  • The FDA had many failures during COVID-19. The first big one was with testing, both with the FDA and the CDC. Others were the decision to delay the approval of Pfizer and Moderna vaccines (by about 4-6 weeks), and the decision not to approve the AstraZeneca vaccine, which hasn’t had any transparency. Finally, there was a complete lack of experimentation with human challenge trials. What all of these share is there has been very little transparency and not much good reporting on these issues. There have not been any thorough investigations from journalists, and we don’t really know what’s going on. Before attempting reform we need to first go and find out what went wrong during COVID-19. We need a non-partisan investigation of all of these issues. We need to utilize Freedom of Information Act requests. We need to find out how Trump was involved, why approvals took the amount of time they did, etc.

Dr. Natasha Vita-More

  • Cosmetics does not need FDA approval pre-marketing. It only needs post-market approval if the company says something in their marketing materials that could be misleading. There are many doctors pushing crack cosmetic treatments and behaving in a very “loosey goose-y”. I have a hard time understanding how they get away with these things, unless there are big-monied interests behind them.
  • We all know about Theranos. In 2015 they got FDA approval for one of their tests. There’s clearly an imbalance here – many life-saving treatments struggle to get approval, but a company which is completely fraudulent like Theranos was able to get approval. [My response: This is a great point! Theranos did receive approval, but only for their Herpes test. If I recall correctly, this test was done with conventional laboratory equipment rather then their special “minilab” device, a fact which Theranos hid from investors. Theranos also utilized a loophole to sell tests without FDA approval.]

Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party.  You can find him on Twitter at @moreisdifferent, where he accepts direct messages. If you like his content, check out his website and subscribe to his newsletter on Substack. 

A List of Possible FDA Reforms – Compilation by Dan Elton

A List of Possible FDA Reforms – Compilation by Dan Elton

Daniel C. Elton, Ph.D.


I have ranked these according to my own perception of which have the most support among DC bureaucrats and members of congress.

  • Improving transparency. During the COVID-19 pandemic the public has been kept in the dark regarding how key decisions were made, such as the decision to issue an EUA for hydroxychloroquine, the decisions that pushed Pfizer’s EUA from early November to late December, and the decision to require additional Phase III data from AstraZeneca which delayed their EUA by at least 3-4 months. Currently the FDA keeps much of the information relevant to decision making confidential. In theory Freedom of Information Act (FOIA) requests can be used to obtain some information, but in practice FOIAs are slow-walked, may require litigation, and take years to resolve. There are many possible ways to increase transparency at the FDA, some of which are outlined in this recent article in STAT News. 18 specific recommendations can be found in this journal article from 2018. One of people referenced as a top candidate for FDA Commissioner, Joshua M. Sharfstein, is a poor choice when it comes to implementing other reforms but has been a leading voice calling for more transparency.
  • Reciprocity. If a drug/medication is approved by a regulatory agency in a different country which has equivalent standards to the FDA (for instance agencies in the UK or Japan, the European Medicines Agency (EMA), or Health Canada), it should automatically be approved by the FDA (and vice versa). Reciprocity would save both taxpayers and companies a lot of time and money. Imagine if the AstraZeneca vaccine had been approved on January 1st, a few days after the UK approved it. It’s easy to see that tens of thousands of lives would have been saved, especially when you consider it would have been given to the most at-risk first!  In 2015 Senators Mike Lee and Ted Cruz introduced the RESULT Act, which is primarily focused on implementing reciprocity.
  • Making the agency independent from the executive branch. It’s hard to insulate the FDA from political concerns as long as Congress controls the FDA’s purse, but it could at least be removed from direct interference from the executive branch by making it an independent agency like the FCC or Federal Reserve. There seems to be wide support behind this idea right now and recently four former FDA commissioners all endorsed this idea in an interview.
  • Rolling reviews. It should not take 3-4 weeks from the submission of an EUA application until a decision is made, especially when thousands are dying every day while waiting for vaccines. According to Dr. Marty Makary, a professor of public health policy at the Johns Hopkins Bloomberg School of Public Health who has conducted over a hundred clinical studies, the FDA “could have done the approval in 24-48 hours without cutting any corners”. Likewise, the approval of drugs and therapies after Phase III trials have reached an endpoint should not take 6 – 18 months. While the FDA does engage in a back and forth with companies prior to when they submit their paperwork for an EUA or approval, they do not use rolling reviews. Due to their rolling review systems other countries like the UK were able issue EUAs for COVID-19 vaccines faster than the FDA. Rolling reviews should be the norm, and the submission and analysis of trial data should made as streamlined and as efficient as possible without compromising the integrity of the analysis.
  • Tiered approvals. Doctors who want to provide new drugs to at-risk patients currently have to wait 5-10 years for lengthy Phase III trials to conclude and then another 6 – 18 months for the FDA to carry out their review of the trial data. Tiered approvals would allow a lower level of approval after just Phases I and II, freeing up treatments to those who need them most. The centrist Niskanen center has a white paper which suggests four levels of approval (see also their op-ed in The Hill).
  • Expansion of Right-to-Try. Federal right-to-try legislation was passed in 2018. However, it is very restrictive, and patients need to have met a number of strict requirements before they can try new medications and treatments, greatly limiting its utility.
  • Treating aging as a disease. Currently it is illegal to market an FDA-approved product as a treatment for aging. Even though aging is a harmful biological process, it is not considered a legitimate “indication” for a drug or therapy by the FDA. In other words, the FDA doesn’t view aging as a “disease” and therefore anti-aging treatments fall outside their mandate. Some specific aspects of aging are also not considered as legitimate indications. The FDA is currently operating in an inconsistent way as some conditions which are due to the aging process can are considered legitimate targets, such as osteoporosis and menopause, but others, like sarcopenia (age-related muscle loss /frailty), are not.  Many experts, including David Sinclair, have spoken out about this issue. Some companies have found ways to get around the FDA’s restrictions, such as by using certain metabolic markers to track the degree of damage from aging. However, the impossibility of getting FDA approval for therapies that directly slow down or repair the damages from aging greatly dis-incentivizes industry R&D investment in this area.  Fortunately, with advanced gene and stem-cell therapies on the horizon, the Congress and the FDA have already taken a few steps towards being able to review and approve anti-aging drugs and therapies. The 21st-Century CURES Act, for instance, mandated the creation of the Regenerative Medicine Advanced Therapy designation at the FDA.
  • Challenge trials in emergency situations. Many people, including a group of legislators, lobbied the FDA to give companies the go-ahead to do challenge trials, but there was no action. Thousands of volunteers for COVID-19 challenge trials signed up with 1daysooner.org but were unable to participate as they had wished to. As a result, data on vaccine efficacy was obtained much slower than it could have been.
  • Use of the proactionary principle for all drug & therapy approvals. The FDA should publish a transparent, quantitative, scientifically informed, and structured cost-benefit analysis for each regulatory action performed, which estimates the expected quality-adjusted life years (QALYs) saved versus risk of QALYs lost for both the action and inaction. The analysis should be made public, ideally sometime before the decision goes into effect. Crucially, the analysis should enumerate the risks and benefits of granting an approval and the risks and benefits of not granting it. See Max More’s overview of the proactionary principle and his chapter in The Transhumanist Reader, where he presents not just a principle but an entire framework for rational decision making. The key reform here is to make it mandatory that decision making at the FDA be highly structured and quantitative so it under less sway from political concerns and cognitive biases. If such a framework for rational decision making was in place it’s unlikely the FDA would have decided to delay Pfizer’s Emergency Use Authorization (EUA) from early November to December 11th, a decision which cost tens of thousands of American lives.
  • Free to Choose Medicine with a Trade-off Evaluation Database.  In brief, Free to Choose Medicine would create an additional track after Phases I and II to allow doctors to prescribe new therapies to at-risk patients who are unable or unwilling to participate in a Phase III trial. Patients in the Free-to-Choose Track would be mandated to submit data to a trade-off evaluation database, creating a trove of valuable real-world data (this could be genetic, biomarker, and adverse events data, for instance).  See this excellent podcast interview with Bart Madden for more information. 

Figure from Bart Madden, “Free to Choose Medicine“, The Heartland Institute

 

Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party.  You can find him on Twitter at @moreisdifferent, where he accepts direct messages. If you like his content, check out his website and subscribe to his newsletter on Substack. 

Not Classing Aging as a Disease is Not a Major Problem – Article by Steve Hill

Not Classing Aging as a Disease is Not a Major Problem – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by at the Life Extension Advocacy Foundation (LEAF) on July 19, 2018. In this article, Mr. Hill does an excellent job explaining why the lack of the definition of aging as a disease under the FDA is not so bad as is sometimes feared. Personally, I do not agree with this. Relying on off-label use is not a good idea because that is much slower of a process than doctors quickly seeing that a drug has FDA approval. Once the FDA considers aging as a disease, pharmaceutical companies will quickly enter this arena and make increasingly better drugs. Mr. Hill makes some excellent points, though, and I highly recommend this article. 

~ Bobby Ridge, Assistant Editor, June 29, 2019

A common concern in the community is that the FDA, the EMA, and other bodies, such as WHO, do not classify aging as a disease and that this poses a problem for developing therapies that target aging. However, this is not really as serious an issue as some people would suggest; today, we will have a look at why that is.

Why this will not stop progress

Aging is a variety of distinct processes, damages, and errors; therefore, simply treating aging in clinical terms is not a viable endpoint. For a clinical trial to be conducted, it requires a verifiable indication, and aging is too general for the FDA and EMA to classify it as a disease.

It also is not a major challenge for damage repair-based approaches, such as those proposed by SENS and the Hallmarks of Aging, as these approaches are not focused on an all-in-one therapy with the indication of “aging”. They are based on a strategy of dividing damages into manageable groups and developing a suite of rejuvenation therapies that addresses each of them.

No single therapy will reverse or halt all of the aging processes when used alone, nor will it prevent all age-related diseases that accompany them. So, to have aging as an indication in any clinical trial would be pointless for any damage repair therapy.

Researchers are free to target aging processes

That said, researchers are very well aware that the processes of aging, which lead to the familiar diseases of aging, are a problem, and this is where the focus lies. There has been considerable effort to classify these processes and precursors of pathology as diseases themselves.

A prime example is the inclusion of sarcopenia (frailty and muscle loss) in the World Health Organization International Classification of Diseases (ICD) a few years ago thanks to lobbying by members of our community. Adding more general codes to the ICD that include these aging processes and precursors is an ideal solution, as it could potentially make it easier to organize trials and develop drugs that target the aging processes.

Back in June 2018, the World Health Organization released the new International Classification of Diseases (ICD-11). The previous version, ICD-10, was published in 1983, and the new ICD-11 will likely be the standard for years to come. The new ICD-11 now includes the extension code “Ageing-Related” (XT9T) for age-related diseases, and this should go a long way towards making focusing on aging easier for future drugs and therapies. Again, this is thanks to work by members of our community, who have spent countless hours researching and pushing for change.

Most aging hallmarks are very clearly linked to specific age-related diseases, such as beta-amyloid protein and malformed tau in Alzheimer’s, lysosomal aggregates in foam cells in atherosclerosis, and alpha-synuclein in Parkinson’s disease. Companies are perfectly welcome to target these aging processes directly, and indeed more and more researchers and big institutions are doing just that in order to treat age-related diseases.

Therefore, not classifying aging itself as a disease poses few barriers to developing therapies that address aging; it’s simply a case of working within the existing framework. UNITY Biotechnology is a prime example; this company is targeting senescent cells and applying its method to multiple age-related diseases; as everyone gets senescent cells, these therapies will be broadly applicable once they become available, and off-label use is likely to expand rapidly.

Also, rejuvenation therapies could, at first, be licensed as treatments for genetic disorders, even though the root cause of the pathology underlying those diseases is not aging. An example of this is the inherited mitochondrial disorders, known as mitochondriopathies, many of which are caused by mutations in the mitochondrial DNA (mtDNA). While these mutations are inherited and are not the result of age-related, deleterious damage to the mtDNA, the same repair-based approach can be applied: the allotopic expression of the protein in the nucleus, as proposed by MitoSENS, could potentially be used to repair the mtDNA allowing normal cellular function to resume.

The majority of damage repair therapies, if not all, could be developed as therapies for diseases with accepted indications and verifiable endpoints, which should satisfy bodies such as the FDA and EMA. Therefore, whether regulatory agencies perceive aging as a disease or not is of no consequence to the development of rejuvenation biotechnologies that address the aging processes.

This does not mean regulatory changes are not needed

Even though classifying aging as a disease is unnecessary, significant reform in the regulatory system is still needed in order to encourage investors and companies to put the time and money into researching and developing rejuvenation therapies.

One area in need of reform is the establishment of aging biomarkers, which indicate the repair or removal of age-related damage, as acceptable endpoints for rejuvenation therapies. Studies that use these biomarkers would also need to include long-term follow-up studies to ascertain the effects of a therapy over a longer period of time.

This would deviate from regulators’ normal requirements that therapies have to prove an effect on hard outcomes to be approved. In an ideal situation, patients should get rejuvenation therapies long before they are in immediate danger and once diseases have manifested, but this makes trials more time consuming and more costly to run.

However, back in February 2018, the FDA published a new guidance document detailing how early-stage Alzheimer’s patients might be identified, which, if accepted, would represent a significant change in policy and a step in the right direction. The document suggests that the results of imaging tests or suitable biomarkers could be enough to consider Stage 1 Alzheimer’s patients as suitable subjects for clinical trials.

This is a positive move as it means that therapies can be tested on people in the very early stages of Alzheimer’s rather than on those who have already suffered considerable if not irreparable damage to the brain, damage that no therapy could hope to address alone. This could mean that these early-stage patients could enroll in a clinical trial and take a therapy that could potentially prevent the disease from ever progressing further or reaching the point where cognitive decline begins.

In the case of repair-based therapies, it would then be a case of demonstrating that the early stages of Alzheimer’s disease were improved via the removal or repair of the underlying age-related damage, and suitable biomarkers would show this.

Moving with the times

Another area where regulatory bodies have struggled is keeping up with the rapid march of technology and medicine. Technologies such as gene therapies have struggled to gain traction due to an antiquated regulatory framework struggling to cope with them. Thankfully, this is also being acknowledged, and the regenerative medicine advanced therapies (RMAT) framework published earlier this year seeks to address this issue and make large-scale changes to how its regenerative medicine policy framework operates as a whole.

According to new FDA regulations, a drug is eligible for designation as an RMAT if:

  • The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and part 1271 of Title 21, Code of Federal Regulations;
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.

While the FDA created these new guidelines, we joined forces with the Niskanen Center to submit comments to the agency so that it would hear the voice of our community.

Conclusion

Aging not being classified as a disease by the FDA, EMA, etc. is not a major issue; the real need is for policy changes that make developing drugs and therapies that target the aging processes easier and more financially viable. It is good that changes are being made to current frameworks and that progress will almost certainly continue in these areas.

Meanwhile, we can continue to support the development of repair-based approaches to aging knowing that such therapies, if they work, will be approved even in the current regulatory landscape.

Steve Hill serves on the LEAF Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.