Has drug development in transplantation been stymied?

Organ transplant patients are concerned the drugs they take to survive can cause other health problems like cancer and diabetes.

And yet, the medications haven’t improved in decades.

Why has drug development in transplantation been stalled?

Ken Newell, transplant surgeon at Emory University Hospital. He served as president of the American Society of Transplantation from 2014 to 2015.

William Fitzsimmons, advisor to the Transplant Therapeutic Consortium. He has spent 29 years in the pharmaceutical industry including developing transplant drugs.

Genevieve Morgan, kidney transplant recipient from Portland, Maine.

Part I

DEBORAH BECKER: Today in America, more than 100,000 people are waiting for an organ transplant. Also today, just like any other day, approximately 17 of those people will die while waiting. For those lucky enough to get a transplant, they'll have to take immunosuppressant drugs for the rest of their lives. And these drugs come with a lot of side effects.

GENEVIEVE MORGAN: Weight gain, GI issues and inflammation, sleep issues. I have a lot of bloating and that kind of thing and weird food related stuff. Travel is hard for me. Infections are really hard. I've had sepsis twice. My bones ache. Headaches, blurry vision, ear ringing.

BECKER: This is Genevieve Morgan. She's 57 years old, married with two grown sons, and lives in Portland, Maine, where she's training to be a counselor.

She got her kidney transplant almost six years ago, and she's been on immunosuppressant drugs ever since.

MORGAN: The immunosuppressants are like chasing a fly in your house with a tennis racket. You get the fly, but you damage all this other stuff while you're chasing the fly.

BECKER: Along with the side effects, these drugs can also cause secondary diseases like diabetes, high blood pressure, or cancer.

But without the medications, Genevieve's transplanted kidney wouldn't survive.

MORGAN: Every day I'm happy for the extra days I get, but I don't believe that quantity of life is the only thing that matters. I feel like quality of life also matters.

BECKER: And yet, there isn't a single immunosuppressant drug that addresses a patient's quality of life.

In fact, there hasn't been a new immunosuppressant drug for transplants since 2011. And patients like Genevieve Morgan want to know why. This is On Point. I'm Deborah Becker. Today, we're talking about post-transplant drugs and what's holding up potential new medications.

Genevieve Morgan found out she had kidney issues almost by accident. Around 2010, she decided to get life insurance. She had a physical. That's when she discovered that she had really high blood pressure. And she was sent for a CT scan.

MORGAN: They found all these cysts in my kidney. First of all, I became completely ineligible for any kind of life insurance.

And I was diagnosed with an incurable, inherited, genetic disease that would kill me eventually unless I got a transplant or dialysis.

BECKER: Genevieve was diagnosed with polycystic kidney disease. She couldn't have been more surprised.

MORGAN: I had been studying to be a yoga teacher. I was working for a functional medical practitioner as a writer and an editor.

I was a wellness editor. I didn't even take Tylenol. I was a huge advocate of Whole Foods and healthy living, long before it became as trendy as it has become. As a vegetarian in my twenties, all of this.

BECKER: Genevieve was 43 years old then. She had a lot to think about.

MORGAN: I was really scared of the idea of having a transplant because of the immune suppressants, and the long-term side effects.

To be on prescriptions for the rest of my life seemed so alien to me at that point. I didn't know if my spirit could take it long term. So for a long time I thought, maybe I'll just let nature take its course and I'll die in my 50s, that's the way it's going to be. I had a nephrologist who said I had about 10 years before I was facing end stage renal failure.

BECKER: At that time, Genevieve's two children were 10 and 13, and she says she decided to get treatment because of them. They needed their mother. It was eight years later, in 2018, when Genevieve was told she needed a new kidney. She was fortunate to be able to get one relatively quickly.

MORGAN: Most people have to wait at least six to eight years in my region in the Northeast.

It's more like eight to 10 years, but because of my general good health and how well I had taken care of myself up till then, my biological profile scored at such a high rate. My search got opened to out of my region and into the national database. All of a sudden, kidneys from every state might be available to me.

So I was only on the list for 10 months, which is a miracle.

BECKER: The transplant went well, but the years since have not been easy for Genevieve. She's had countless infections and complications and is typically hospitalized about three times a year.

MORGAN: The other thing about immunosuppressant is you're always fighting with one hand tied behind your back.

So even in recovery, even if you have a stomach bug, it takes you twice as long to recover.

BECKER: She takes five pills a day. Each one comes with their own list of side effects. The things Genevieve mentioned earlier, insomnia and achy bones, issues she says her doctor doesn't take too seriously.

MORGAN: He's sympathetic, but I think there is a little bit of, what do you want? (LAUGHS)

Like you're here and this is the best we can do right now. I don't want to sound like I'm complaining, but I also want to be like, is it really the best we can do? Because kidney transplant programs right now track half-lives of kidneys. But you could be in a wheelchair and have your kidneys still working, and you would still be considered a success.

You could basically be in a coma and if your kidney was still working, you would still be considered a survivor. But that to me isn't living, that's not surviving.

BECKER: Polycystic kidney disease is genetic, so Genevieve worries her sons are at risk of contracting it, too. She hopes if her disease is passed down to them and a transplant is needed, the drugs of the future will give her sons a better quality of life than she's had.

MORGAN: If they have to go through the same thing, if they're lucky enough to get a transplant, more attention should be paid towards helping people live a better life with transplant, not just a life.

BECKER: That's transplant recipient Genevieve Morgan from Portland, Maine. Joining us to talk about the world of post-transplant drugs is Dr. Ken Newell. He's a transplant surgeon at Emory University Hospital. He served as president of the American Society of Transplantation from 2014 to 2015. He's joining us from Atlanta, Georgia.

Welcome to On Point, Dr. Newell.

DR. KEN NEWELL: Thank you, Deborah. It's a pleasure to join you today.

BECKER: I wonder when you hear a story like Genevieve's, how common is it for patients to tell you that they're struggling with these post-transplant drugs that they must take for that transplanted organ to survive?

NEWELL: Unfortunately, it's probably the rule rather than the exception. And as she mentioned, it's difficult for us because we don't have a lot of options. We can make some small adjustments, but every adjustment we make simply changes the side effects. It doesn't really get rid of all the side effects.

BECKER: And how common is it, when Genevieve said, I don't want to complain, but, on the one hand, I'm sure many patients are grateful. They have an organ. They're alive. Is it difficult for patients to feel that they have a right to say, but my quality of life is suffering here?

NEWELL: I think more and more over the last years, we've heard about that as patients become free to say, it's good, but. I recently saw a patient and I just bumped into her outside the hospital setting. I said, wow, you look great. How are things going? She said a lot better than they were, but I still have a lot of problems.

And they almost feel guilty sharing that with you, because as they'll say, I'm one of the lucky ones. I got a transplant. So many people aren't able to, but yet it doesn't mean that everything is perfect.

BECKER: Tell us about the drug options that patients have now, post-transplant. Is there one and it may not work in a lot of people.

And you mentioned adjustments. Or are there several, and it's a trial-and-error period to see how the side effects are with each patient?

NEWELL: The vast majority of patients get three drugs post, or following their transplant, and those drugs have existed anywhere in one form or another for between two and four decades.

Now, there've been slight engineering improvements in the drug to try to address this side effect or reduce it. But those are the three drugs that are mostly used. So there isn't a lot of wiggle room. When I tell you that, in the first-year post-transplant, probably 70% of people get those drugs.

In a few cases, you may drop one drug, or you may add another, but most people get the same drugs.

BECKER: And tell us the primary goal.

NEWELL: The primary goal, as these drugs were developed, because of the way they're evaluated and approved, is to decrease the risk of rejection in the early post, early after a transplant.

BECKER: And without, you must take these drugs, right? If you don't take them, it's likely that organ will be rejected.

NEWELL: It's almost certain that it will be lost in fairly short order.

BECKER: And so then what are the primary side effects that you hear from patients, or reasons that you might have to make an adjustment?

NEWELL: Somewhere around 20% of patients will develop diabetes following the transplant, as a result of the medications. The mainstay of the medications we use as a class of drug called calcineurin inhibitors, they were developed and introduced into practice in the '80s. Those cause kidney failure.

For instance, there's a fairly high rate of kidney failure following liver and heart transplant simply due to the drug that prevents the rejection of the organ. As we heard, there are like problems with headaches, tremors. It can cause high blood pressure or make the existing high blood pressure worse.

Certain cancers, particularly like skin cancers, are much, much more common due to the anti-rejection medications people take.

BECKER: And we're going to get into how these drugs are evaluated and how new ones might come on the market. But I wonder, if they do come with these series of problems, these drugs, what's the upside?

What do we know about how these drugs improve the life of an organ and make sure that it can stay with someone for a certain amount of time?

NEWELL: If you look at transplant around 1980, the rate of rejection was 90%. That doesn't mean all the transplant organs failed or were lost, but they needed to be treated with even more aggressive anti-rejection medications.

And the likelihood of a kidney transplanted in the late '70s, early '80s, surviving a year, was under 50%. With the introduction of this new class of drug, the calcineurin inhibitors, those numbers basically flipped. You got an organ that survived with about a 80% probability at a year and rejection rates fell to less than 50%.

So in terms of the organ working and keeping you off dialysis and alive, the medications are quite effective. They just come with a lot of unwanted side effects, and in the end aren't quite up to the task of making that organ last as long as we'd like it to.

Part II

BECKER: People are able to live longer with transplanted organs.

However, these new medications that allow that to happen also have a lot of side effects, like diabetes and cancer and high blood pressure. So I'm wondering, do we have the science now to improve those post-transplant drugs and eliminate some of those side effects?

NEWELL: I believe the answer is that we almost certainly do.

The problem is you need to change your target. We've become very good at hitting the target we're aiming at, which is how is the transplanted organ doing it a year? But that's not the target, as we've heard, that patients are really interested in now. If you think about a young person, maybe 20 getting a transplant, it's almost taken for granted that a year, things will be okay.

But you start saying, what about five years, 10 years, 15 years? To most of the patients we transplant, that is a really important question that we don't address. And drug developers can't necessarily develop drugs to address that need. Because they don't have the right endpoint to get a regulatory approval.

BECKER: I just want to say, is part of this because these organs didn't last so long before, and these drugs allowed that to now become possible, is this sort of a way that the system needs to evolve to accommodate the fact that we have these new medications? Would you say that? Or would you say it's a lot more complicated than that?

NEWELL: No, I think you're correct. I think now we're hearing from patients who are beginning to feel comfortable saying, thank you. It's wonderful that I got a transplant, but I've still got problems and I need you to help me solve these problems, or at least reduce them. And now that we're hearing that, I think we're much more in tune with the need to develop better drugs to treat people after their transplant.

BECKER: I want to bring someone else into the conversation here. William Fitzsimmons is an advisor to the Transplant Therapeutic Consortium. He spent 29 years in the pharmaceutical industry, so he can tell us a little bit about developing new drugs. And he did help develop some transplant drugs. Some made it to market.

Some didn't. Bill, thanks so much for being with us on the show today.

WILLIAM FITZSIMMONS: Hi, Deborah. It's my pleasure to join you.

BECKER: Can you tell us what you think is the holdup, really? We heard a little bit from Dr. Newell, but I'm wondering what you think is the holdup to making sure, if we do have the science to improve transplant drugs, what do we need to do to get them better, to eliminate some of these side effects and still make sure that people can have organs that survive, transplanted organs that survive as long as they do?

FITZSIMMONS: I think the key thing that we need to do is to incentivize the pharmaceutical industry to bring those new therapies into transplantation, rather than taking them into other diseases or conditions, or in addition to taking them into studying other diseases or conditions. To do that, they need a pathway to show improvements from a regulatory standpoint with the FDA, over the current therapy.

Also, that those, we need an endpoint that would be indicative of long-term outcomes. As Dr. Newell indicated, will that kidney continue to function for many years post-transplant? And so that they can promote those advantages of their new therapy over the current standard of care.

BECKER: It would seem that there are tens of thousands, hundreds of thousands of people who have transplanted organs.

Why isn't this being done?

NEWELL: We're trying to do it, but I think that right now we haven't been successful yet in convincing the FDA and taking action to qualify a new endpoint. And that qualification of that endpoint allows us to take advantage of some of the expedited pathways that other conditions are taking advantage of with the FDA to bring new therapies more quickly onto the market.

BECKER: And so when you say endpoint, what, explain to our listeners what exactly you mean, and ideally how you would like that endpoint to change in terms of developing new drugs.

FITZSIMMONS: The endpoint, Deborah, is a measure of efficacy. So how does the drug work and what can we measure in a clinical trial?

So in this situation, as was pointed out, the current endpoint really revolves around, is the organ being rejected, is there rejection that is occurring? What we want to do is change it to an endpoint where we're looking at the health of the kidney and the immune response to the kidney.

BECKER: And what about looking at the side effects?

Where does that fall into the picture in terms of an FDA review?

FITZSIMMONS: The FDA always will look at the side effects of a new medication. However, it's not the primary endpoint that this determines whether a new drug is approved. So it is included in the labeling of the drug, but it's not the primary reason for approval.

We have to first show that the drug is efficacious, and then also that the safety is evaluated and balanced with the benefit and risk of the new drug.

BECKER: And I wonder, if you could say, really, how does this compare to other medications for other disorders? We certainly hear about things like accelerated approval for types of cancer medications, and different things happening from the FDA.

Why is that not happening with post-transplant medication, do you think?

FITZSIMMONS: Yes, I think that the key part of that is in oncology, where there is the most, new therapies being brought forward, they're able to use what's called a surrogate endpoint, meaning can they measure the efficacy of the drug before looking at the survival of the patient. And that allows them to take advantage of the accelerated approval pathway through the FDA.

So for instance, in cancer, they're able to look at the shrinkage of the tumor, and that's a predictor of whether the patient will live longer. And that allows them to bring a drug onto the market, oftentimes using only one clinical study, and much quicker than if they waited to measure survival.

BECKER: So is it FDA policies that you would say are mostly holding this up or what, why do you think that there's such a stall on these particular medications?

FITZSIMMONS: The FDA policies exist. What we need to do is be able to take advantage of those specifically in transplant. And I think that the stall is that the division that reviews transplant drugs is very interested in continuing to use the traditional endpoint that's based on rejection.

So we need to augment that endpoint and also use a new endpoint. And the other stall, I think, is that in other areas, there's lots of clinical trial data that we can use to leverage and bring a new endpoint forward. However, in transplant, we've scoured the world, literally, to get all the information on thousands of patients and provide that to the FDA.

So the FDA is interested in more clinical trials, but there aren't any more to actually supply to them. And if we want to wait for five-year outcomes, we can't start a new trial now and say, we'll get back to you in five to 10 years.

BECKER: Why is the division that reviews these post-transplant drugs interested in continuing to use the one-year endpoint or that endpoint when we know that perhaps it should be expanded, and we certainly know from patients, that they feel that their quality of life could be improved if, in fact, there were other ways of dealing with this. Why hold on to that?

FITZSIMMONS: What we've heard from them is that there's a number of reasons. One, it's historically been what they've used for approving other drugs, so it's difficult to change that precedent.

The other thing is that when we give an immunosuppressive drug, we're trying initially to prevent the rejection of the organ. So they want to make sure that they continue to measure the amount of rejection that occurs in the transplanted organs. I think those are the two key things. And when a patient has rejection, it does prompt treatment with other drugs.

So there's certain side effects that are related to the treatment of rejection. We've really said to them, it's fine to keep the current endpoint, but what we need is to add an addition to it. Another endpoint that can actually suit the needs of the field and the patients better.

BECKER: Dr. Newell, I wonder do you, are you in agreement for the most part with what Bill is saying here?

Would you like to add to that? Do you think that this is an issue with endpoints and there is work that needs to be done here? And how would you describe it? I wonder.

NEWELL: I would say that without a new end point, a new way to identify drugs that are better than what we have, the field can't progress.

If we continue to use the end point we're using, I suspect that over the next 10 years, nothing really transformative will come to transplant.

BECKER: Bill, you actually developed transplant drugs, right? In one, about 10 years ago, you worked on a drug that looked like it was going to work, but it didn't. Can you tell us that story?

FITZSIMMONS: Sure, yes, I have worked on a number of different transplant drugs. I was working on one that in monkey studies, which are the key animal studies we do to predict efficacy in humans, it was able to extend survival and worked in preventing rejection of transplanted kidneys in monkeys. However, the company decided not to take it forward into transplantation and instead have developed it for rheumatoid arthritis, and it's approved in a number of other countries.

But one of the main reasons that it was decided not to move forward in transplantation is that because we had only the current endpoint, we didn't see a way to show that our new innovative therapy was better than the current therapy. And the current therapy is relatively inexpensive and it's available generically.

So the company didn't see a way to have an adequate return on investment and saw a better commercial value actually taking it into autoimmune diseases like rheumatoid arthritis.

BECKER: Explain why someone would need that end point, why the pharmaceutical industry would need that end point changed for a new therapy to be worth the cost to pharmaceutical drug developers.

FITZSIMMONS: There's several reasons. One is that the company needs to be able to tell the doctors, as well as the patients, about the advantages of their new therapy. And that's really based on the label that's approved by the FDA. And there's very strict regulations in the U.S. on what the companies can promote.

So we need to be able to get in the label the advantages of the drug so that we can tell patients and physicians about those advantages. So that endpoint has to be in the label, has to be part of the approval of the new therapy.

BECKER: And in the case that you were just telling us about, in terms of the determination to go away from post-transplant drugs and toward rheumatoid arthritis, explain why that's different for the drug developer, is it simply because there's no FDA nod of approval on that, so there's more money in the rheumatoid arthritis end of things?

FITZSIMMONS: There's still the regulatory FDA approval process that exists for the drugs in rheumatoid arthritis, but there are several key differences currently compared to transplant. One, we're able to see the efficacy in transplantation, we perform relatively long clinical trials. Secondly, we're able to demonstrate the advantages of that superiority of a new rheumatoid arthritis drug over the existing drugs with the end points we have in rheumatoid arthritis.

And thirdly, the FDA oftentimes will allow a pharmaceutical company to only perform what we call one pivotal or phase three trial. That's the final clinical trial that's done before the FDA approval. Whereas in transplantation, historically they have asked for two pivotal or phase three trials, and each of those trials not only takes many years to complete, but also take about a $100 and $100 million in order to support the conduct of that trial.

BECKER: I asked Dr. Newell this question, I'd like to ask you as well. Do we have the science right now to improve these post-transplant drugs?

FITZSIMMONS: I believe absolutely we do. The immunosuppressive science is there.

We have innovative new therapies. They unfortunately have been only developed in other therapeutic areas like rheumatoid arthritis or autoimmune diseases historically. Those drugs oftentimes are safer than our current drugs, that we can see that they don't have the kidney toxicity, the diabetogenicity that was described earlier.

So we'll afford a better quality of life for patients. So there's no doubt the science there exists. What we need to do is couple that with the regulatory science, meaning how can we bring those forward through the FDA approval process.

BECKER: And I wonder how does the U.S. compare to other countries without an FDA and without these endpoints that are getting in the way? Is the U.S. the largest market and is something similar happening to patients who are in other countries? What do you say about that, Bill?

FITZSIMMONS: Yeah, no doubt the U.S. is the largest market. So the pharmaceutical companies look at the U.S. first and foremost. You'll see most new therapies are approved in the U.S. before any other country.

The other, every other country has some form of a regulatory body like the FDA, just under a different name. But their rules about how drugs are promoted and how they're approved are completely different oftentimes than the FDA. For instance, we were able to have a new endpoint for kidney transplant, approved by the European Medicines Agency.

Much more quickly than we have been through the FDA.

BECKER: But, and so in patients in Europe, are they taking similar drugs? Are they taking newer drugs? What's happening in terms of their experience with post-transplant care?

FITZSIMMONS: Most patients around the world are taking similar drugs, the drugs that Dr. Newell described. There are a few therapies that have been approved in Europe that are not yet available in transplant in the U.S. But, by and large, the companies will first and foremost try to develop in the U.S. And if they're unable to, it actually may stifle innovation around the world because they don't see the return on investment to bring it into other countries.

Part III

BECKER: Many patients say that the side effects from these drugs are so severe that it's hampering their quality of life.

And right now, these drugs are measured by the quantity of life, rather than quality. So what's key, both of our guests say, is changing the way the FDA looks at the effectiveness of some of these drugs long term. And I do want to say, we did get a response from the FDA regarding some of these things.

And part of what the FDA said was, quote, it does not develop drugs or drug endpoints. The response also pointed out that the FDA has held workshops with the participation of several stakeholders to try to create a platform for discussion and innovation about new post-transplant medications. And the FDA statement pointed out that the agency, it says, is committed to the integrity of the so-called accelerated approval program to bring safe and effective drugs to market. Now we briefly mentioned this accelerated approval program earlier in the show, but I wonder, Dr. Newell what do you say to that statement from the FDA that it is encouraging input from a variety of stakeholders to improve some of these post-transplant medications?

NEWELL: I would certainly agree that it's not the FDA's job to design and study new therapeutics. Their job is to evaluate the data that is presented in support of a new therapeutic.

In terms of the workshops, it's good to hold a workshop, but Bill can correct me. I believe there have been six workshops over the last more than decade. And as the patients pointed out at the last one, nothing has changed over the last decade. So to hold a workshop is a good thing, but it has to benefit the patients, or they will grow tired of attending and expressing their opinions and then having nothing change.

BECKER: And why? Why hasn't it changed? If you're hearing from all these patients that they're having these difficulties, what's the main holdup?

NEWELL: I think there's a concern that with any new innovation, there's risk. If you look at something that occurred during my lifetime, the change from big open surgeries with big incisions, to less invasive surgeries with smaller incisions, there was a risk there.

Clearly the patients benefited and they preferred that, and that drove change. I think there's always risk when you propose a new end point that it may not work as well as you want. And you can say this end point isn't perfect, but if you compare the end points being proposed to what we currently have, it's night and day difference.

So I think the concern about what if it's not perfect is overshadowing the, what we have now is totally inadequate for the patient's needs.

BECKER: Bill, it's my understanding though, that there has been some update really on changing end points, right? And the FDA is at least considering that.

Can you explain?

FITZSIMMONS: Yes, that's correct, Deborah. We have submitted, it was called a qualification plan. There's three steps in getting a new endpoint qualified by the FDA and we're in the middle of the second step. And in March of this year, the FDA accepted our qualification plan for review, which should put us on a timeline to hear back from them in September of this year, on their acceptance of that plan.

And then we would move to the third stage of the qualification.

BECKER: What's the third stage? Then what do you do? And how long does that take?

FITZSIMMONS: Yes, the third stage is submitting all of the data and really, we've submitted it all already, but we answer any additional questions the FDA has, submit all of that additional data.

And the hope is that in 10 months, the FDA will take action on that, but it's hard to hold them to a timeline, because the timelines are very loose in terms of how the description of that qualification.

BECKER: So 10 months from now, next spring, could it really happen that there could be a new endpoint or no, there's more sort of procedural things to go through there?

FITZSIMMONS: What we would, if they accept our qualification plan in September of this year, then we would submit the next, this third stage. And so that would probably be submitted in early 2025. And then that would take 10 months. So we're really looking at the end of 2025 in the best, most optimistic case.

BECKER: So it's a ways away.

FITZSIMMONS: Yes, but we're on the path and we're still optimistic.

BECKER: Are there new innovations that you're hearing about that maybe aren't necessarily changing the endpoints of these post-transplant drugs? But, we've heard certainly, there's a lot of attention on new therapies, pig organs, stem cells, stem cell transplants and using those and what they might mean for these medications.

Are there other ways to help transplant patients?

FITZSIMMONS: Absolutely. I think I look at it as there's two key things we need to do. One is increase the number of organs available to patients. As you heard, there's 100,000 plus organ transplant patients that are on the waiting list currently, and pig organs for the long term may be one of the solutions of that, but that's a still a long ways away.

I think more immediately what we need to do is do a better job in keeping the current transplant organs functioning well for a long period of time and having those patients feel better, have safer drugs with better quality of life. And there are therapies that are currently in development to try to improve the outcomes that are clearly safer, and could have a better tolerability to the patients, but they're in early stages of what we call phase one and two of development.

BECKER: What's the best way, do you think, to increase the number of organs? And Dr. Newell, I'd like you to answer that too, because we've been hearing about this in a variety of ways, and I think it is a real issue for folks and it's part of the debate here, because I do think, as we heard from Genevieve at the start of this program, it makes people reluctant to complain because they feel so fortunate to even be able to get an organ.

What do you think needs to be done to try to increase the supply of organs available for transplant?

NEWELL: I believe that there are a number of things happening, and there are more organs available now than there have ever been. Some of those are through recent advances in how organs are stored. Once someone donates an organ, it has to get from where that person is.

To where the person who needs it. And so they've come up with a technology called machine perfusion, where they can put the organs on pumps, and it helps us test the organs and make sure they're okay. And it gives us more organs, because sometimes the organs will even show signs of improving their function.

So I think that's an important step. You mentioned organs from pigs, so called xenotransplantation. I think education around the population is important. All these things will help get more organs, but it's not an 'and, or,' it's a 'yes, and.' So we need to get more organs, but about right now, about 15% of all kidney transplants performed are performed in people who had a transplant already and lost it. So not only does that surgery become more difficult, but it consumes organs or takes organs that could go to new people. So if we could prolong the survival of transplants, that would also increase access to organs for transplantation.

BECKER: Bill, do you have anything to add to that?

FITZSIMMONS: No, I think that's absolutely right. We need to do both increase the input into the system, meaning more organs. The immediate things are machine perfusion and expanding some of our use of the organs, that we oftentimes will discard organs and some of them may be able to be used in the long term, increase the use of pigs.

And then decrease the output, meaning the loss of organs, so that patients don't have to be re-transplanted.

BECKER: And do you feel that the FDA is listening to patients as much here? I'm wondering if more voices would help, right? Is patient input considered if patients are having difficulties with these medications, and how is that weighed in this whole process of evaluating these post-transplant drugs?

FITZSIMMONS: I think the FDA is listening. There's no doubt through their workshops, they're hearing from patients and they're hearing a voice that's more clear and loud now than ever before, which is a very good thing. I think translating that though into action, in terms of how to bring new therapies forward, is where we're somewhat stalled at this point.

And that's the connection that we hope to make, using these new measures or new endpoints.

BECKER: Is that the most significant thing that you believe will lead to improvement, or are there other ways that this process could be improved for more transplant patients?

FITZSIMMONS: I think it has to be a combination of things.

We need everything from the investment community to say transplantation is a good place to put our money and invest for new therapies. We need the pharmaceutical companies and biotech companies to bring their new therapies forward. And we need the regulators around the world, including the FDA, to say we want to facilitate that process and look for ways to help bring these new therapies forward that are both safe and effective.

BECKER: And Dr. Newell, what would you say to that?

NEWELL: I would agree completely with Bill. I think we need to make it easier for the companies and the investors to see a path forward in transplant right now. The problem is every trial that's done takes a decade. It costs a lot of money, as Bill mentioned.

And at the end, what I'm allowed to say is, I have a new therapy that's no worse than the old therapy. And that's not compelling, right? You want to say it's better. And we need to have the regulatory authorities help us come up with endpoints where we can say this is actually better.

BECKER: Do you think that lawmakers or Congress should get involved to try to help change some of these things, maybe fund new initiatives, maybe spur the investment that you're talking about. Is that even a possibility here? And I'd like both of you to answer that. Bill, what would you say first?

FITZSIMMONS: I think that from the FDA perspective the main thing that they are limited by is the resources in order to work on different programs like qualifying a new endpoint. So I think lawmakers can help provide the FDA the resources to do that, because they're overworked. They have many things to do at the FDA, and their priority is the new drugs where there's a strict timeline on when they have to act. So that things like the work we're doing in endpoints falls to the bottom of their work pile because there's not as strict a timeline and they're so overburdened with other things to do.

BECKER: What's an estimated cost of something like that? When you say not enough resources, are we talking that doing this and changing this from what it's been for decades would cost millions of dollars? What would you say?

FITZSIMMONS: No, I don't think we're speaking about millions.

I think we're talking about adding a head count, more people at the FDA, particularly in the qualification program, to help move this process forward. Because what they're doing is utilizing expertise within the FDA that are doing many other jobs at the same time. So we just need more people with the expertise to evaluate this within the FDA.

BECKER: Dr. Newell. Do you think that there's room here for lawmakers or Congress to try to step up and change things?

NEWELL: There are probably others who can better speak to that than me, but I believe there is because, they set priorities. What Bill is really saying is what are the priorities and that determines what resources are allocated.

And so to me, it seems if Congress recognizes the log jam that's created here, the barriers to innovation and how that's impacting the health of people living in our country, they can reprioritize and help the FDA get the resources it needs to more expeditiously. It is a daunting timeline.

The project that Bill's working on started, correct me if I'm wrong, Bill, but formally back in 2017, and we still are in the midst of it.

BECKER: Do you think that there are patients, Dr. Newell, who don't get a transplant or maybe don't get another transplant because of the experience that they've had with these post transplant drugs? I believe certainly, I don't know that anyone would say, I don't want to be transplanted. I know though that there are people who contemplate that, and as we heard, more and more people, there have been a number of surveys of patients done, where we ask patients, what do you think? And they really say it's not just how long I live, it's the quality of my life, and how does it impact my family, and it's a much broader question than just am I alive?

BECKER: Would you like to, what's the main thing you'd like to see happen going forward?

NEWELL: For me, I do believe that to get the patients the new therapies, we need to change how the therapies are evaluated. Right now, every drug that's approved is approved based on the ability to maintain or slightly improve the outcome at one year.

That's not what the patients are interested in. I don't believe that will encourage pharmaceutical companies and investors to support transplant. I think we need an outcome that measures something important to patients, which is a longer term outcome, as well as a quality-of-life outcome.

BECKER: And Bill, in the last minute, what would you like to see happen?

What's the most important thing that you think would be significant going forward?

FITZSIMMONS: I think the most important thing is that we see transplant as a place to bring new innovative therapies, that everyone is working together in the ecosystem to do the right thing for patients and transplant recipients.

If we create that, like it's been done in oncology, we'll have a very robust pipeline of new therapies for many of the different conditions in transplantation. And that takes all of us working together, regulators, scientists, patients all rowing in the same direction.