A Last Wish Fulfilled

Rembrandt is considered as one of the greatest Dutch painter ever. His Renaissance paintings have inspired generations and will inspire generations to come.

Many hope to see these famous paintings sometime in their life. An unnamed patient wanted to see the Rembrandt paintings, but ALS was a seemingly impassable barrier that couldn’t be broken. The museum was often crowded, and wheeling in a hospitalized patient wasn’t an option.

Kees Veldboer, a former ambulance driver, formed the Ambulance Wish Foundation. When the Dutch charity heard about this woman’s last wish, they decided to fund the venture.

After arranging with the museum, a special audience after hours was arranged. The woman was brought into her own private viewing to fulfill her wish. Along with three other terminally ill patients, they enjoyed the legendary paintings for the last time.

Man Who Invented Ice Bucket Challenge Honored

Social media sites were exploding this last summer with the latest trends, but one trend took the prize for the most popular. The ALS Ice Bucket Challenge. According to Forbes, the Ice Bucket challenge has raised over $100 million. That outstanding amount of money was all masterminded by one man.

Pete Frates was a Division I baseball player for Boston College. He was elected the team captain in 2007, and went on to play professional baseball. Tragedy struck when Pete was diagnosed with ALS at age 27. Instead of wallowing in self-pity, Crates masterminded an idea that has changed the ALS world. With the Ice Bucket challenge, Frates was able to bring national attention and money to ALS.

Frates has been a lifelong Red Sox fan. He played the Red Sox in college, and was able to hit a homerun in Fenway Park. This year, the only jersey worn was #3, Pete’s Boston College jersey number.

Pete was unable to attend the game, but his family was able to attend. Instead of Frates being on the field, it was his wife and seven month-old daughter Lucy. His wife Julie said seeing Lucy on the field “might be one of the greatest joys of his lifetime”.

To donate to the “Pete Frates #3 Fund” visit: http://petefrates.com/index.html#.VPjvwns5AqM

ALS Crowd Radio Episode 10: Dr Jonathan Katz, M.D., Sutter Pacific Medical Foundation

Dr Jonathan Katz, M.D.,

Sutter Pacific Medical Foundation

Interview Date: February 26, 2015

Dr. Katz speaks about the complex issue of the right to try for patients with ALS.  Can an ALS patient be allowed to try an experimental drug before it is approved by the FDA?  Dr Katz explains why it can take up to ten years for drug development, and the reason for exclusions in clinical trials.  He shares his vision for a shared database of information between the 90+ ALS clinics around the country that can make a huge impact for the ALS community.

ALS Crowd Radio Show with Dr. Katz

Full Transcript:

Seth: Hello and welcome to episode 10 of ALS Crowd Radio. I am your host, Seth Christensen. I have the delight to introduce a new co-host today, a fellow pal, Whitney Hill. Whitney, can you introduce yourself?

Whitney: Sure. I am Whitney Hill, a friend of Seth’s. I have been diagnosed with ALS starting in November of 2012. I am still not quite sure that I agree with that diagnosis, wishful thinking maybe. And I live here in the Salt Lake area. I’m a wife and a mom.

Seth: Thank you, Whitney, for being here. We have the pleasure of having Dr. Jonathan Katz here with us today as our guest. I’ll have Whitney introduce Dr. Katz.

Whitney: Dr. Jonathan Katz is the director of neuromuscular program at Forbes Norris ALS Center in San Francisco, one of the largest centers on the West Coast. He is currently the national principal investigator in multicenter clinical trials of — I don’t want to butcher this — Rasagaline and diaphragm pacing. He’s also the current president of ALS-RG, a national organization of clinical investigators that is tasked with improving efficiencies in clinical research.

Dr. Katz has written over 70 peer-reviewed articles in ALS and in other neuromuscular conditions and has given numerous lectures on ALS. He is the co-director of a busy social media website for neuromuscular physicians, which focuses on the dissemination of knowledge among those practicing in this area.

Prior to joining the Norris Center, he was an Associate Professor of Neurology at Stanford University School of Medicine. He did his neuromuscular training at the University of Texas, Southwestern Medical Center in Dallas, his neurology residency at University of Washington in Seattle, and Medical School at Tulane in New Orleans. He is a graduate of Johns Hopkins University. He is currently an Adjunct Professor of Neurology at Kansas University Medical Center. And even with all those accomplishments, probably the biggest one is that he is also could be the twin of Woody Harrelson. So all pretty impressive feat.

Seth: Thank you, Whitney. And Dr. Katz, are you with us?

Dr. Dr. Katz: I am here.

Seth: Great. Would you like to refute anything Whitney said?

Dr. Katz: I think she got it pretty much on the number. I’ve been all around the country, and I feel like the only city I miss was Salt Lake City.

Seth: Well, we will have you out there after this show. Thank you for joining us today. We are thrilled to have you.

Dr. Katz: Nice being here.

Seth: Thank you. Before I get to our main topic, I’d like to try to talk about your overall work in ALS and your focus areas. What can you tell us about what excites you in ALS?

Dr. Katz: Well, I come from the background of being the clinician. First and foremost, I have a clinic in San Francisco. I see a lot of patients so I try to take that patient perspective as much as possible and try to understand what people want and what the right thing to do is. Obviously, this is a frustrating disease in the sense that we’re trying to find a cure and trying to move the world forward.

So I see also the research side of everything. From a research end, personally I am interested in clinical trials and how to bring a drug that might be successful in ALS as fast as possible and as efficiently as possible to people. So I think a lot about that issue. I am not, just to be clear, a scientist in ALS, but I think there’s a lot of work to be done by the scientists to figure out exactly how the disease is happening. I try to stay in touch with that topic as much as possible. But I think it’s probably the most important part of all the puzzle together when it comes to solving this thing.

And then I think right now the things that excite me is I am directing, as you heard, a couple of clinical trials nationally, one with the diaphragm pacer and the other with this drug, Rasagaline. I am doing one with Jeremy Shefner who is in Arizona, and the other with Rick Barohn who is in Kansas. My pet project of all is I am very interested in data right now. So I’m working on a project that hopefully will allow all the ALS clinics in the country to start entering common data like if you were at a bank or something like that and you wanted a mortgage, say, at Wells Fargo or some bank, they wouldn’t let all the mortgage brokers enter your information haphazardly anyway they want to do it.

So I am working on a project right now that would get eventually the 90 or so ALS centers in the county to understand that it would be very useful to the field if we are all entering the same clinical information every time we saw a patient that would go into a database and help us begin to understand the disease a lot better. So that’s kind of where I am right now.

Seth: Well, we are excited about those things as well. And thank you for your work in those areas. I can tell our listeners that Dr. Katz is one of the most forward-thinking leaders in the country in data. We hope to have a lot more time on our future episode to address that topic in and of itself. Thank you for that intro.

Speaking on the first point, the bringing of drugs to market and to the ALS community, what is your interest in the right to treat or right to try?

Dr. Katz: Well, it’s a timely topic, right to try. It’s super interesting topic because for the one part it’s becoming reality. It’s a law. So the right to try is basically a legal movement that will give people the right and give companies the right to use drugs or give out drugs or sell drugs as long as the agent has been proven effective, it’s been proven safe in a Phase I trial.

So it’s an interesting movement because from the one side, from a patient perspective, it’s going to give people more opportunity to get to resources that they might think are important. On the other side, it’s going to make it easier to get drugs that haven’t necessarily been proven effective. So it’s a super interesting topic in the sense that I think it’s really important for people to understand all the different sides of this, the potential for good but also the potential for risk. Hopefully today, if people want to ask questions, we could open some of that discussion.

Seth: Great. I know here in Utah, there was bill passed yesterday on the right to try. So timely it is. We are told that we are having a significant static. I think we would like to try and call you back, Dr. Katz. If you could hang up and we will immediately call you back.

Dr. Katz: Hello.

Seth: Dr. Katz, we hope that this is better.

Dr. Katz: Sounds better.

Seth: All right. Great. And my apologies to our listeners. We hope that will clear up some static. So as I was saying, I know this is happening in a number of states including here in Utah yesterday. How from a regulatory perspective is this rolling out?

Dr. Katz: From a regulatory perspective, I think you have — I hope I answer the question the right way — but on the one side, you have some organizations tend to be somewhat conservative leaning, pushing the right to try from this standpoint of the government. In this case, the government would be perhaps considered the food and drug administration. From their point of view is that the government has been a bit of an impediment in slowing down process, making it hard for drugs to come to market. They should basically get out of the way. I use the term a conservative worldview because it tends to be that it’s the conservative side of the various think tanks or the conservative think tanks that ask for the government to get out of the way and decrease regulation in general.

In this particular case, there is a nice fundamental relationship to be had with people who really do in the immediate present of the world want these drugs because why would you want to go to the process of having to volunteer for clinical trials. And maybe you don’t meet criteria for clinical trials or you can’t get into clinical trial because there’s not one in your area or you’ve had the disease too long or for whatever reason or you don’t have enough abnormalities to have the disease to be qualified for a study or your disease is too mild or too severe and so on and so forth.

And then the other thing about people, PALS, is that they’re going to be in a clinical trial. The trial is going to take two or three years to get done. That’s not really fair that you’re being asked to enroll in a clinical trial for the benefit of the next generation of people who are struck with ALS. So there’s a real desire for people to get their hands on drugs. So the movement is a natural relationship between PALS and conservative think tanks.

So that’s I think who is pushing the legislation for the most part. It’s a legislation if you think about it that your liberal agendas are going to be in favor of because how are you going to say no to a bunch of people who really have a legitimate need for something. And on the other hand, the conservatives are going to be in favor of it because it’s anti-regulatory. So I think from a legal standpoint or from a fundamental legislative standpoint, it’s got pretty sound backing. Now, there is another side to it which I am sure somebody is going to ask me about.

Seth: No, please go ahead and preempt them. We will open the callers in a bit. But if you want to talk about this, go ahead.

Dr. Katz: So in a way, I am not a legal scholar but I am somewhat familiar with the term the slippery slope. So everything sounds good on its face that we can make drugs available to people, but there as some downsides to it because now if you cut out the regulatory center of the relationship between companies and patients, what’s to prevent a company from giving a drug that’s safe. I mean safe is not a very high bar really or charging money or getting people excited about taking a drug if you don’t even talk about the fundamental issues of cost or the fundamental issues of who’s going to pay for this. But now you have the issue of a drug that hasn’t been proven getting into people’s hands.

Well, how hard can a company push before you get into false advertising in that situation? What kind of press releases could a company release that gets people excited about something? If you think of any clinical trial or new drug, the reality is the only way you’re going to get people to fund the trial is if you get them very excited about it in the first place. But the reality is most drugs we’ve tried are not effective, so you need the hype machine turned on to get the drug even to be studied and to go to trial. But you really have to know the answer before you are really going to trust people having the drug.

So it opens up the door to a lot of behaviors that regulation might serve a purpose to prevent where a company over-hypes a drug and people get overexcited about it. The other potential downside to that is we have to enroll people in clinical trials still to find out if drugs are actually effective, like that problem doesn’t go away.

So what follows from that is we have to either be really clever in how we study drugs given the right to try. So if I am going to live in a world where everybody gets drug who wants it, I really would like a deeper ability to be able to predict the outcomes in the patients that are getting the drugs so I could see if what the expected outcome gets altered by the drug. So maybe with the right to try we have an outside chance especially something super effective of seeing it work because we’d say, “Hey, this was supposed to be the course of ALS patients.” But in fact they got the drug and it seems like the PALS all did better than we would have expected.

So we’d have to have some sort of ability to track what’s going on under the right to try to really get to understand things, and I am not sure that’s built into the legislation. The other solution with the right to try, I mean there’s a lot of things tossed around would be to say you have the right to try provided you don’t meet criteria to be in a trial. But then that’s not fair to the people who are in the trial because still it would only be the people who meet criteria that would be subject to having to possibly get placebo and that kind of thing.

So all I am really saying is there are definitely a lot of sides to this discussion I think things that get out into legislation. Personally, I don’t think that’s the right place to make decisions. I am not a big fan of government myself. So you really don’t want people who are not that educated in this topic and businesses pushing stuff through lobbyists in making decisions. I think the last thing I will say is the ALS community, ALSA, some of the other organizations, and you can ask me later about specific examples, but they’re in a bit of a though situation saying, “We really want to do trials the right way, but we really want patients to have access to drugs as much as possible.”

So trust me when I say there’s a lot of really good and really smart people in our field that are thinking really creatively and really openly about how we’re going to make this work for everybody. I am big fan of letting the people who are the stakeholders like the patients and some of the doctors that are involved in this being at the forefront of the decision making. Once it gets into legislation, I am always a little bit queasy that things are going to get out of our hands pretty quickly and who knows where it goes from there. But that’s just about as much background as I could give you right now.

Seth: Great. For those new to the drug development process, this is an old conversation. It seems that two gaining factors are time and money. We wouldn’t be having a conversation about being treated outside of trials if trials moved the speed of light and were all well funded, but that is not the case. Any thoughts on the time cycle required for drug development?

Dr. Katz: You hear all sorts of things and you just use the two magic words: time and money. And in ALS, I’ll answer the question two different ways. You could look at the time in a well-funded large pharma company for how long it takes a drug to get to market and those guys have to go through the initial development of the drug, all the preclinical research in test tubes and in laboratory rats, all the safety studies that have to go on after that to make sure that a new molecule is not going to hurt people. And the safety studies have to start off at the animal level and sometimes companies do see things, go slightly wrong.

And then after assessed risk, if you should keep things going forward, if maybe there is a little problem in an animal model and then you have to try small studies in humans, either with or without the condition you are interested in to make sure it’s safe and small, studies that require now communicating with the doctors and all the IRBs and the federal IRBs, meaning the review boards at all the individual institutions. And then you have the FDA to contend with. And then after all that is done and you’ve pumped in all the funds to get that started, then you might have to go to a small clinical trial to see if something is effective. And that could take a year and then you have to go back to the FDA after that. And then after you’re done with the FDA, now you have to do the really big study to prove that the drug is effective which could take a year or two.

And it’s an incredibly long and incredibly expensive procedure. I think it’s all geared towards diseases that are much less fearful. If you have a high blood pressure medicine and you’re going through that kind of process, who cares? Everybody is getting a high blood pressure taken care of fairly well. But if you have a disease like cancer or ALS, there is not really time for that sort of process so we need other strategies. So that process I just described could take 10 years.

And then to go back to what I said at the beginning, the other side of the whole thing is that in ALS sometimes it’s not big pharma that’s starting the process. It’s a little company that’s out there like in Silicon Valley or somebody who had an idea with the molecule and they want to test it. So there they’re going to have to scrounge up their money to do even the first stages of something. And by the time that they get done with the small trial which is already fairly far off the road, they’re broke and their funders may have disappeared. Significant time passed or the people that are funding them think a couple of million dollars is a giant amount of money to put up for risk.

So what happens is you get these results that might be optimistic in early phases, but you can never do the trial because the company can’t raise the funds for the later parts of the trial. And what happens there is we go through all the statistics and we say before we do the study, just like we do for everything, here’s what would be an important outcome and we create these terms like P values and this and that. And the study gets done and the issue has nothing to do with anything you’ve talked about for the first two or three years of putting the project together.

Now, you are just talking about is can the company get money to do the next phase of their trial? And if they can’t, it’s done. If there’s not enough excitement on the outcome, they can’t get funds for the second trial. In our particular field like a couple years ago, you had this gigantic study from Biogen on dexpramipexol that came out negative. After that, because it was such a big negative outcome, people get scared about putting the funds up for the next drugs. So immediately, after that we get into a period where everything slows down again because the optimism wanes because of a negative study and money is a big part of it. And like you said, time is a big part of it. So there really are so many different factors that go into this.

Seth: And the trial process, is a very complicated thing.

Whitney: I want to tell the listeners that if they want to call in with a question, the number is 516-590-0362, and press 1 to indicate that you have a question.

Dr. Katz, I have a question regarding trials from a patient’s point of view. I don’t understand why you basically have two years from diagnosis to be included in any trial and after that you don’t qualify. Why is that?

Dr. Katz: We got asked that question all the time, and there’s a really good answer to it from the perspective of somebody doing a trial and it seems really unfair. Obviously, to start up a thing, if we forget the trial altogether and we have a new drug out there, why can’t everybody just have the drug?

Whitney: Right.

Dr. Katz: Trial to people who have the disease for more than two years. But here’s the but side of it. Here’s what happens when you are doing it.

Whitney: Dr. Katz, we’re going to have you start your answer to that again. We lost you for a minute.

Dr. Katz: Oh. Where should I start?

Whitney: Right after I said, “Why is that?”

Dr. Katz: Okay. That’s great. Let me hit my rewind button for a second. So I think I start here. So anyway, the answer to that question — before I even answer the question, I just want to say it sounds really unfair that we cut the access to a drug in a clinical trial off at two years. So in other words, people who have the disease for more than two years just can’t get into a trial. Sometimes it’s three years for the cutoff. Sometimes it’s two years. And on its phase, from a really simplistic fairness perspective, one can argue it’s really wrong.

Now, if we don’t look at it from that perspective, if we look at it from the perspective of everything I just talked about which is the money that goes into a trial, the funding that goes into a trial, if I am the person paying for a clinical trial, I want to find out if a drug that I am interested in is effective or if I am a government funding agency that’s just going to say — I’ll make a number — 2 million dollars to somebody who can put together a trial for me, I have a limit to what I could spend on this trial. So I really do have to begin to think how best can I understand if the drug works at the end of the trial? How do I make sure that I am going to not spend those 2 million dollars and at the end of the day have no answer to my question?

Two million dollars which is often just a rough amount of funding for an early trial, sometimes it’s more, sometimes it’s even less, sometimes it’s 7 million dollars or whatever, but what you are talking about early trials here, at low levels of funding, I really do have to take into account the risk that I am going to blow it without answering the question. It just turns out that if you have the disease for more than two years and you are not so sick at two years that you are in desperate condition, that would mean you are a slow progressor. Your progression is very slow because you’ve lived a long time and you are still in pretty good shape to be part of a trial. So you are a slow progressor.

From a purely statistical point of view, the problem with slow progressors is that they’re not going to change much over the course of the trial or at least there is a big risk they are not going to change much over the course of the trial. If I am interested in studying whether a drug works, I don’t want to spend — again I am not talking about fairness, I am just talking about determining if a drug works. I don’t want to spend a lot of my resources on people that aren’t going to change over the one year I am observing them in trial because you don’t get any information from those people as far as just the raw statistics.

What I really want is people that are going to progress over the course of a year, and I am going to compare them, the people who are on placebo to the people on drug, and I am going to see if I could alter that progression. If I put a lot of people in my trial who are going to show no change over a year, then I really run the risk that since the change is so small, I have to put more people in the trial to be able to see that, to see the difference if I could slow it down with the drug if the change is very small which means I have to pay more. And as you know, the way I started this discussion is these trials frequently don’t have enough money to do that.

So it really is about what we call statistical power. It’s the ability to see that we’re making a difference. Now, on the other side is we also cut off the breathing limit in a lot of trials at a certain number and that’s because the other thing you don’t want to have happen is you know somebody in a trial and they pass before the trial is done because then you also lose a lot of information. So it really is one of those things where in the perfect trial — and again we are just talking about the trial itself — we need the kind of like the goldilocks of people that are going to progress enough that you are going to be able to see a difference but not progress too much that they’re not going to make it through the observation period. Does that make sense?

Whitney: Unfortunately, you made it sound so practical. I am kind of bugged. But yeah, that makes sense.

Seth: Now, we come to the topic of right to try, collection of data and proof of validity of a potential drug is a whole other topic. I know that overseas they do agree to treat people under the topic of compassion, but they have the same problem, the data collection and including the overall trial at risk. I know that if you simply go and do a Bing or Google search of the topic, ALS and right to try, you will come up with a number of people suggesting ways of collecting data outside of the trial from those who are using a drug under right to try. Do you ever see that gaining legs or accepting that by the FDA?

Dr. Katz: Well, I think the answer to that question is: absolutely. It’s not ideal. It’s not the best way to study drug. I think there will always be a place for the basic trial like we’re doing it now, but I also think that we could probably think more creatively and find ways to actually capture that information. Now, I’ll say one more thing. For that information, if we’re going to basically say anybody who wants to take a drug which I think is a great goal, we need to think completely differently about how we understand drugs. And I kind of hinted it this earlier in the conversation. If you want to give everybody the drug and know if the drug works, you’re going to have to be much more clever at predicting the outcomes of everybody who gets that drug.

So if I have a patient that comes to me and they say, “My ALS started in 2012 and I think I am in pretty good shape,” well, I could quickly do the math. That’s three years ago and they’re still in pretty good shape. So I probably say in the next three years, there’s not going to be a lot of change in that person. And if somebody comes to me and says, “My disease started at the end of 2014 and I am already in really bad shape,” I could predict that that person is probably not going to do great over the course of the next month.

Now, statistically, we should make the effort to take, say, a hundred patients and hear their stories about what’s happened up to the time they got the disease and be able to predict really, well, if I were to give drugs to these hundred patients, what would I expect the average rate of progression to be in those hundred patients? I think this could be done but we have to put the effort into studying the prognosis in patients to be able to do that. And so far, the problem we have is that most of the databases we have are only patients who have been in trials.

So we have to really extend it to the whole population if we’re going to really be able to make the effort to see what’s going on. We have to get much better at prognosticating and to do that, I think we have to get much better at collecting large amounts of data on patients and to understand this other thing that comes up all the time, their biomarkers. We have to understand what’s in their blood or maybe what’s in their DNA or what’s in their spinal fluid a little bit better to really understand how we’re making things change. I think eventually if everybody starts thinking together, this movement can have some success from a scientific standpoint, not just from an access standpoint.

Seth: Thank you. We’re going to have Whitney read the number again and invite callers.

Whitney: The number to call in is 516-590-0362, and press 1 to indicate that you have a question.

Seth: Now, we have a number of callers on the line. We’re going to pause for a moment to take our first caller. Caller ending in 4475, you are on the line with Dr. Jonathan Katz. Go ahead with your question.

Caller: Dr. Katz, I’ve got a question about on the right to try. Is there a differentiation between treatments that are approved for non-ALS issues versus brand new drugs, for example, Lipitor or Flomax or Viagra? Somebody got an idea that that might be effective and they started a study on it. Since they have to be FDA approved, is there an easier path of having right to try for those types of things or is it even an issue since you might be able to get your physician to prescribe it?

Dr. Katz: That’s a great question. We had that come up before. A few years ago there was Tamoxifen which is like a breast cancer drug that affects estrogen that people were super interested in trying for ALS. And if somebody out there wants to call me on it, maybe I am getting mixed up but I think it was Tamoxifen. And we had a bunch of patients because it a prescription drug. So we had a bunch of patients saying, “Can you please start me on that drug?” So we would. So it’s not really what right to try is about. Right to try is really much more about non-FDA approved drugs.

Now, I’ll add on to that that sometimes the insurance companies aren’t exactly going to pay even though something is FDA approved. So if we take what you just asked and make it a little bit more complicated which is, let’s say, let’s look at the diaphragm pacer which is probably a $25,000 to $50,000 procedure where you need a surgeon to put something into the body, there the FDA for certain ALS patients has approved the procedure but the insurance companies don’t always want to pay for it. So Medicare pays for it. A lot of the insurance companies pay for it. But Kaiser out here in California won’t pay for it.

So that get into that’s not really what the concept of right to try is, but it does get into the issues downstream of will insurance companies even pay for a drug or a procedure if it’s too expensive and whatever? So you don’t really always have the right to have what you want. But if it’s a cheap drug like Lipitor and you have this conversation with your doctor saying, “I’d like to try this,” I don’t see a problem there whatsoever. But the two big show stoppers are the drug is expensive or the procedure, so who’s going to pay for it? And then obviously, if it’s not FDA approved, that’s really what right to try is about.

Genervon has a drug right now, for example, that people want to get their hands on. And obviously, you’ll know about this from looking at the internet or from being part of it. But that’s really what right to try is about; it’s getting your hands on drugs that are not FDA approved.

Caller: Yeah, okay. Thank you.

Seth: Thank you, Caller 1, for the great question. We will take another caller ending in 0311. Caller 2, you are on the air with Dr. Jonathan Katz.

Caller: Hi. Thanks, Seth. I have a couple of questions. One is the right to try seems somewhat vacuous because for clinicians there’s still IRB to go through and the FDA. The FDA simplifies the compassionate use form from an hour to 45 minutes, but still they need to be complied with because state laws don’t trump the federal regulations. So is there any significance to right to try when it comes to experimental stuff?

Dr. Katz: Yeah, that was a very smart question because you still have the FDA in a way. But I don’t think that the groups that are pushing right to try have necessarily stopped the push at the state houses, right? I think there’s more push that’s going to go on and we’re just seeing the beginning of this movement.

Caller: Oh, so they want federal law?

Dr. Katz: Right. So the pressure is going to end up on the FDA eventually. I don’t know which way it’s going to spin out at the end of the day. I don’t know if there’s going to be a permissive FDA at the end of the day that says, “Yeah, people have a right to try. We’re not going to get in our way.” Or if the FDA is going to say exactly what you just brought up which is the current world because we’re not there yet where they’re going to say, “No, you can’t. Even though you have the right to try this drug you still need a permission slip from your doctor and the IRB of whichever center is prescribing it.”

Caller: People like ALS Emergency Treatment Foundation, they say the current regulations are fine because there’s expanded use trial provision for FDA and that was taken advantage of back in the day of AIDS treatments before for ACT and so forth and that’s enough, and that’s what needs to go forward instead of right to try.

Dr. Katz: Well, that is true, but then you have the issue where — in the expanded use question, it’s a totally different variable because now you have the question where all right, I am a company and I am interested in getting my drug approved. I could theoretically make expanded use part of this proposal. I’ll talk to the FDA. I’ll make sure that people who can’t be part of my trial can get access to the drug for whatever reason that I think that that’s the right thing to do.

But from a company’s perspective, that’s expensive and it’s also really risky because you are opening up the use of the drug in a way that’s out of control of your study. So you are taking on a lot of risk that could end up shooting you in the foot as you are going through a process because somebody has a side effect in Tuscaloosa, Alabama, and the study is not in Alabama and they end up in a hospital and it gets into the press. How do you know how that’s going to spin out? And it takes effort to get the drug out there.

So the easiest way to do it for a company is to say I am going to get my permission slip to do the drug in the trial, and I will only do what I am allowed to do on that permission slip. I am not going to put any resources into anything else because in fact all the resources I have need to go into the trial right now. So from a concept of risk, from a concept of cost, expanded use doesn’t always make sense. The AIDS epidemic was a little bit different in the sense that the voices were a little bit louder. I think in reality it was bordering on unethical to not give people expanded use because you are starting to really have successes of these drugs.

So ALS, we haven’t even talked about it, but we also have the issue that people in drug trials in the back of our minds or in the back of some people’s mind, they almost hate saying this, are always a little skeptical still that a drug is going to work. So AZT in the AIDS era, I think there was like a really legitimate belief that it could end up being effective. So the ethics just vary between the diseases if that makes any sense for reasons of belief of whether you think a drug is going to work or not, the deepest innermost levels.

Caller: Thank you.

Seth: And thank you, Caller 2. I believe our Caller 2 was a friend from Boston. Thank you. We would invite the other callers on the line to press 1 if you have a question for Dr. Katz on not just the right to try but anything related in his work in ALS.

Dr. Katz, thank you for the conversation so far. You brought up the topic of Genervon. Can you speak specifically about where we are in that trial?

Dr. Katz: Yes. I think anything I am going say about Genervon I am going to say carefully because it seems like a bit of like a multifaceted social event right now. But it’s a good case study on everything we’re talking about because I’ll say it from the standpoint of an honest ALS researcher. I look at the work that’s been done which I can summarize is their drug which has moderately interesting underlying scientific basis has been given to a really small number of patients. Their data to say, “Hey, this thing is really great,” is not there. In reality, I don’t look at what Genervon has done and say, “Boy, this is the most exciting thing and it’s going to work.”

So that’s just the background. I don’t want to completely throw the idea of Genervon’s drug out without saying I think drugs need a chance to be proven whether they work or not. But I just want to say that where Genervon is right now, they haven’t gotten over a bar to say, “Hey, this thing is great.”

Now, you moved away from the science for a second. What’s interesting with respect to our time is that now we have social media. It’s possible to raise a very loud voice about something. I think you start putting together what the ALS community wants with respect to drugs, which is to give people hope, to give people a chance to use a drug to make drugs available, to not have to deal with the FDA for 5 or 10 years. And you put together a company that is willing to press that button and willing to be part of that discussion, about fundamental access, instead of a company that wants to work with the proof of principle that a drug works in the usual manner.

You have a bit of a powder keg that could explode because historically the companies, because of the FDA, because of regulation, have stayed on the side of the scientist, of the clinical scientist. But here with the media, not surprising for companies, again money is involved or whatever, you begin to press some buttons that are a little different than the buttons that were pressed in the past. In this case, it’s the social media buttons and it’s the feeling that we’re not giving patients everything they need fast enough which is legitimate. And when you press those buttons, maybe you do end up approaching the FDA differently. Somebody sooner or later is going to get somebody at the FDA to say, “You are right. We have to make the access a lot greater and we have to give people a chance.”

But the flipside of that, like we said earlier, is well maybe Genervon starts pushing the drug in directions that we’re not used to, not through clinical trials but through access and maybe they get to profit from that. So you can see where I am going. It really is complicated and the last thing I want to see is for people — I want people to have access. I think that’s important. I think we have to think about it. But just to have a lot of access out there without a strategy to prove the drug is effective, it raises a lot of questions and in fact a lot of fear that somebody is going to take advantage of the system at some point.

So the last thing I will say is the ALS Association really tried to address this with a letter to let everybody know that the organization cares about this. But an organization that’s funding clinical research historically and wants to see the right thing happen which is both access and learning about drugs, has to be somewhat — is in a difficult position to say the right thing to everybody which is we really want you guys to all have what you want and we want drugs to be studied faster. But I think the steps forward from all of these are all about really going to be all about helping everybody think a little differently about how we’re going to study drugs as with the fighting right off the bat or letting a lot of hard feelings out there saying people don’t want what’s for the best. We just have to balance two slightly conflicting ideas.

Seth: Very much so. Thank you. We will now go to another caller. Caller ending in 6431, please go ahead with your question. Caller 3 ending in 6431, you are on the air.

Caller: Thank you so much. Dr. Katz, I just really appreciate your presentation. It’s so informative and considering the different directions that this whole issue has to be observed. I just need to express my appreciation for you to be sharing this with a group such as alscrowd.org because if I understand this organization, their great direction is to improve data collection. And when you talk about the necessity with expert data collection, DNA awareness, the whole issue of understanding each patient were they to undergo one of these trials or results or one of these opportunities, the results, I think that data collection is paramount.

I am so excited to have you associate or have you speak through an organization such as alscrowd.org because that is such a push on their — if I understand the organization correctly, that is their main thrust is to coordinate the data to make this applicable, to make it worthwhile for everyone. And I appreciate that so much. Thank you for working with them and sharing with us your information.

Dr. Katz: Well, thank you for saying that. I will plug both myself and them together. We look at this collection of data as extremely important. If I had to just talk for a second about like where data collection should go on the field, I think it’s a gigantic vision in the sense that, number one, what I said earlier, it’s kind of crazy if you think about it that we have 90 plus ALS centers in the country and everybody is just collecting at the bedside every time a patient comes in. Every week I see 15 ALS patients in my clinic. We’re just collecting notes in all 90 centers completely differently and passing the notes on to Medicare so they can bill. That makes no sense whatsoever. We have this great opportunity.

I mean what’s in a clinic? You have a doctor, a patient, sometimes all the other clinicians. You have the ability to order wheelchairs. You have the ability to — five years ago there wasn’t a computer in the clinic. Now, there’s a computer. You can feed information back to people, educate them on the disease. So we’re not taking advantage of these clinical centers which I think is a giant mistake and we have to fix it. I think a lot of the research we’re talking about, trials would flow from that because you understand patient outcomes better.

But there’s also just like the community that develops from being able to collect data together, and the opportunity for different people to get to know about each other and learn about the disease and learn about outcomes. And then there is all of the other places that ALS could connect to like making wheelchair ordering cheaper or making speech devices better. There’s just a ton to learn by having a structured internet. That doesn’t really go one way where we get the patient’s data because the other way where we can give the patient’s data.

I think Seth has a really great vision also, that’s the second plug, which is to begin to really hook ALS up. My interest is to do it from the bedside but his is to hook up ALS to the rest of the world and to really begin to use some really creative ways to put all this data, genetic information, blood information — I’m probably leaving out a thousand things — historical information, ancestry information to really create a very deep understanding of the disease. I think that’s where things really need to go. So I am glad you brought up that question.

Seth: And thank you, Caller 3. You’ve added us as the data go-to.  I can re-plug Dr. Katz. He is a very forward-thinking on how to get the data, one, standardized at the clinic level; and two, out into the open away from the clinic so that we can actually use that data as a community. And the community is critical here. We need to not reinvent the wheel but instead use all of the wheels that have been invented and use them for what they are designed to do which is solve this riddle. So I thank you both.

We will take another caller. Caller ending in 1034, you are on the air.

Caller: Hi, Dr. Katz. Thank you so much for doing this show today. I really appreciate it.

Dr. Katz: Thanks.

Caller: I have a follow-up question about the data. If you can wave a magic wand and maybe pick one of the most critical pieces, the standard process in clinical trials in drug development is an 8 to 10 year process. Drugs develop for potentially a particular target and it goes through the whole process and that many years later you get an FDA approved drug. What do you see as the biggest shortcut where you can develop hypothesis on a really rapid scale? Because without targeted biomarkers that you are going after in ALS, it’s even more of a challenge.

Dr. Katz: You said it right there. I mean the first answer is to find the biomarkers. It would make things a thousand times easier. If we had something we could just look at that would require fewer numbers of patients because there’s a lot of variability on functional scores, some people decline faster than others, if we had a biomarker that we could just measure, that would be fantastic because we could shrink the size of trials and speed them up. It would be a lot more trustworthy if you just had the blood test to measure things from a distance because when you are measuring functional decline from a distance, who knows what everybody is measuring and whatever.

A blood test is very objective. It’s very fast. So that’s the short answer to the question. But let’s say we don’t have a biomarker for a long time. It starts getting confusing because if you want to study biomarkers during clinical trials, which tends to be what happens, you want to figure out if a drug hits the target every time you do a clinical trial. In others words, your trial gets a lot more expensive, which is going to slow down the speed that you could do trials. So finding a biomarker actually makes it harder to do the other half of what your question was which is to fundamentally speed through trials. You are going to be slowed down until you have that biomarker.

So it just creates a big challenge. I think for every drug that wants to come to market, you have to have a different strategy. I toss this around in my mind all the time, but I think at one level you have to think of the cheap and dirty, fastest trial ever which would be to really understand disease outcomes, you put a hundred people on drug and you just figure out if the drug works and if it doesn’t, forget about it and move on to the next drug. That’s the way you do things fast.

If you have a drug you are really interested in and you have the funding, you’re going to want to learn about is it hitting this target? Learn about biomarkers. And then I think the other piece to it is there has to be a completely separate process to study biomarkers where we’re constantly testing ideas in ALS patients. And again, that gets back into creating the infrastructure at the bedside where we have a lot of station information. And we could take their blood samples or bio samples and give them to interested scientists and study them on a constant basis. What we’re doing right now though, we’re funding one thing at a time over and over again is really haphazard and small and disorganized and we’re not going to get there as fast as we can.

So I guess my answer would be create the infrastructure first that needs to be in place. Communicate a lot better which means having governance and ideas that are tossed about by patients and doctors, the infrastructure governance, and finally I think a real deep understanding of everybody into what our goals are with every single drugs that we could at least speed along as fast as possible. That’s as good as I can do.

Caller: That’s a great answer. But I wonder if it would be reasonable to go backwards and start out with patient outcomes that are working well and drive back down to the, let’s say, five or six of different hypotheses of what worked well and then try to drill down a little bit more on those. I don’t know if that’s possible.

Dr. Katz: Well, I think that that’s actually another really good point because — I am not sure I am going to answer what you said exactly on target. But I do think like another strategy for discovering the disease is to have a really strong hypothesis of what we think are the primary players. It gets into the whole question of what drugs should we be studying. I always envision that there is a meeting of great ALS minds of people that are actually detached from the funding, who would get together and tell us here is the fundamentally unifying hypothesis of this disease that we think is most interesting to test right now and develop drugs towards that hypothesis. I think what you did is bring up a whole another question which is, which drugs should we really be testing, which if we only have limited resources is an enormous question.

Caller: In time. Okay. Well, thank you so much.

Seth: Thank you for your question. We are almost out of time here but I do want to invite you, Dr. Katz, to plug any of your current trials, anything more to share about your diaphragm pacing trial or your drug trial right now?

Dr. Katz: So the diaphragm pacing trial, if anybody has any interest in the diaphragm pacing trial, email Seth, email me. I will get your name and we can see if you’re — after all this I almost hate saying it, but we could see if you are eligible for the procedure. And it’s an exciting procedure in the sense it’s a device that stimulates the diaphragm. And since the breathing muscle which is the diaphragm is super important for the longevity, if you could just make that muscle more functional, you may improve people’s life expectancies.

So that’s why we’re doing the trial. The trial is having a hard time enrolling because it’s a surgical procedure and also because I think some of the super excitement that was there at the beginning is kind of gone away with time. But we’re about 50 patients into 180-patient enrollment. So we’re pushing along. We still think it’s an exciting trial and we hope people would sign up for it. And then Rasagaline is a drug that was helpful in Parkinson’s disease. So we’re looking at it in ALS. It may have slowed down the progression of Parkinson’s disease. And that study is just about done but hopefully you’ll be hearing some results in the next six months or so. We’re done recruiting.

Seth: Thank you. If you could tell our listeners what you said the greatest opportunity to get involved either in your trials or in the ALS community. We’ll wrap up with that.

Dr. Katz: Well, in a nutshell, instead of answering the question exactly as you asked it, I think it’s something that Seth and I hopefully will continue to talk about, but I think we want to use shows like this and we want to use an internet portal to really make people aware of opportunities for trials and actually all of these issues that we’ve talked about. I think that in itself can bring the community together which in a way will make everybody’s voice louder, make people be able to hear the field better, and to make research projects faster and to ensure that we’re going to end up doing the right thing. So if I had to say anything, it’s anything that brings the community together is going to be extremely important.

Seth: Excellent. And lots more kind of on that topic. We want to thank Dr. Jonathan Katz for the time and insights and also, Dr. Katz, for your dedication to the community. We love having brilliant minds on board and it also helps when we really like the people attached to those minds. So thank you for your time today.

Dr. Katz: Thanks so much, everybody.

Seth: And thank you, Whitney Hill, for her exceptional co-hosting of today’s show. We look forward to our next episode. We’ll publish the full transcript from today’s episode in the next week. Thank you for listening.