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Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.
Can you imagine having to get a blood transfusion every few weeks just to continue living? That's what life is like for the 20 to 30000 new patients each year and numerous more who suffer from a condition called MDS. Doctor John Scarlett is president and CEO of Geron Corporation. Doctor Scarlett, welcome to the program.
Dr. John Scarlett:Thanks so much, Moira. I really appreciate it.
Dr. Moira Gunn:Now before we start, I do wanna tell everyone that Geron has a drug which has made it successfully through the phase three clinical trials. We're always saying, how are you doing? Where are you in the phase three clinical trials? And has what we call a PDUFA date, coming up with the FDA, where the FDA hopefully is gonna say thumbs up. It usually says thumbs up, but let's make sure we get there, and that's when we can commercialize and go to market.
Dr. Moira Gunn:But before we do that, let's lay some groundwork. If there's one thing we all need and we we know we need it, it's for our bodies to produce blood cells, good healthy blood cells in the quantities we need. Now we're talking about, MDS today. What is it? How is it treated?
Dr. John Scarlett:MDS, which stands for myelodysplastic syndrome, is a bone marrow cancer that results in inadequate production of blood cells. And in the form of MDS that we're studying, those cancer cells take over the bone marrow and do not produce the normal amounts of red blood cells, which is the oxygen carrying portion of blood that's so important for our daily lives. And so patients with MDS, the version we study, they become anemic and eventually become transfusion dependent. So the goal is, above all, to get them off of transfusions if at all possible.
Dr. Moira Gunn:How often do they have to get a transfusion?
Dr. John Scarlett:So it's a progressive disease, and what might start out as sort of a watch and wait, eventually, these patients sometimes become mildly transfusion dependent, meaning they may only need 1 or 2 units of red blood cells every couple of months. But eventually, they become heavily transfusion dependent. And that's actually a really terrible thing, from a couple of perspectives. 1, they're tethered. 2, they have to be in an infusion center to get those transfusions very frequently, often as frequently as every other week.
Dr. John Scarlett:That entails a lot of logistics, a lot of driving, waiting around for blood to be cross typed and matched. Sometimes the blood has to be brought in from another center because they didn't have the right blood for them. And so they become really dependent on, on, becoming dependent on these transfusions also means they become really hobbled. Their quality of their life, their daily living is really hobbled by that. And so they may take upwards of 10 units of red cells every couple of months.
Dr. John Scarlett:And that in and of itself also causes dangers. Red blood cell transfusions, cause deposition of iron in major, organs, and that can cause failure of those organs. And so there's there's lots of things that transfusions do that you would really like to make people transfusion free or reduce the burden of transfusion as much as possible.
Dr. Moira Gunn:So here's where Geron comes in. This is where you're working. What is your drug doing specifically? Because I know in the overall, you wanna get them off those transfusions. But what is it doing specifically about this condition?
Dr. John Scarlett:So our drug is what is called the telomerase inhibitor. And, you know, all cells ordinarily have a normal life cycle. They get born. They do whatever they do as cells, and then they die in a pretty orderly fashion. And they die after, you know, proliferating a few rounds, and then they then they senescence and die.
Dr. John Scarlett:But cancer cells in general, and these MDS cells in particular in our case, actually have, an enzyme in the bone marrow that is upregulated called telomerase, which causes those cells to continue to proliferate. And as long as that enzyme is present and upregulated, they're going to become, much longer lived and, as I say, proliferate at very high rates. So a telomerase inhibitor is intended to take away that that enzyme's action, and then the cells become more like normal cells, and eventually, the proliferation lowers. They apoptosamine die.
Dr. Moira Gunn:Now if I understand what you're saying is that if I had this condition, these cells would, like, not die filling up my bone marrow. They're not producing healthy blood cells. So over time, I have fewer and fewer of those. And what your drug is doing is it's going in finding those cells and saying, no, I'm afraid you're gonna have to die, which makes room for your healthy blood cells.
Dr. John Scarlett:That's exactly right, Mara. Just as you, alluded in patients treated with a telomerase inhibitor, ideally they become far less dependent on or not dependent on, transfusions to address their anemia, and, lots of other good things happen to them in that regard. So that's a a key goal, of treatment.
Dr. Moira Gunn:Now as I said earlier, you have not only gotten into phase 3, you've completed phase 3. And that meant phase 1 went well, phase 2 went well, and now you really have a good body of knowledge. Tell us about this phase 3 trial. What did you do? Who was in it?
Dr. Moira Gunn:How long did it last?
Dr. John Scarlett:Right. So this was a study that was done in many, many centers around the world, including United States, North American general, also in the far east and certainly in, in Europe. And we took patients who had a version of MDS called lower risk MDS, just as we've described. And we randomized them to receive either Imetelstat or placebo. Of course they could continue to receive transfusions if needed.
Dr. John Scarlett:And so for example, the majority of placebo patients continue to receive transfusions. And then, percentage of patients, that no longer needed transfusions, really was the main outcome of that study, outcome measure of that study. And in our case, 40% of the patients had at least an 8 week transfusion free interval, in the Imetelstat treated or the drugs treated arm as opposed to the placebo treated arm. What's really impressive though is that those patients, actually went on to have, on average about a year of not requiring transfusions. And that's really substantially, better than you could do with any other drugs that have been on the market prior to this.
Dr. Moira Gunn:So that's what leads you to successful phase 3. That's great. Now a lot of people think, well, that means just go out and start manufacturing and distributing it to, medical centers everywhere and and doctors. But the truth is is there's a space between successful phase 3 and this PDUFA date. PDUFA are the letters p d u f a.
Dr. Moira Gunn:They come from the US government act, Prescription Drug User Fee Act. And it has to do with that's the date that the FDA will have absolutely done a whole lot of stuff in reviewing exactly what went on. So tell us, as a company, you get these great results and you get from here to the PDUFA date. What do you do then?
Dr. John Scarlett:Well, the first thing you do is you make an application to the government through the FDA to be allowed to market the product. And we call that a new drug application or NDA. That, generally is filed about a year before you would expect to be be approved. And in that application, which covers literally all aspects of your drug, all aspects of the disease, You make all the arguments why the data, strongly support the idea that the efficacy of the drug is more than adequate and actually that the benefit risk of the drug is strongly in favour of treatment with the drug. And that's the fundamental lens through which the FDA looks.
Dr. John Scarlett:But of course there are many, many, different, angles that are, looked at, in both the efficacy and the safety side of the product. Once you're through that review, if you will, then there's other things that you do with the FDA, which include, agreeing on the professional instructions for use of the drug, which we call variously the package insert, which people would be very familiar with. You get a package insert. Most of the time, you get a prescription drug. It's usually a very large piece of paper that's folded up very tiny and stuck on the, on the, on the, on the drugs container.
Dr. John Scarlett:You also there there's, there almost every aspect of the sale of a product in the United States, via this, via the approval of an NDA is covered in the whole review and approval process down to what the advertising can say and how you can say it.
Dr. Moira Gunn:Now I forgot to ask you how many people were in that last phase 3?
Dr. John Scarlett:Right. There were a 180 people in that last phase 3. And, as I said, they were in a a large, a large number of, of centers around the world.
Dr. Moira Gunn:Lot of people for a lot of months. A lot of months. Well, it's like, guess what? Your PDUFA date is coming right up. June 16, 2024.
Dr. Moira Gunn:You've turned in, I guess, just about everything to the FDA so far, and now you're waiting.
Dr. John Scarlett:Yeah. There's, some back and forth still, but, what I would say is that right now, the company is really focused on being ready to start to sell the product if approved. That would most likely come around the time of the PDUFA date, as you've said. There's a huge amount of activity that's focused on supplying the commercial needs of the market once you do have approval. And you have to kind of anticipate that, right, because you don't wanna get an approval and then not be able to go out and provide the drug to the market, in appropriate way for months.
Dr. John Scarlett:And so we've hired sales reps, we've got a whole commercial team working on the correct messaging and the, access to the healthcare system, which in this country is very complex and requires a lot of people to sort of navigate all the different ways that we end up getting drug to patients and we end up getting information to their health care providers and and hematologists in this case, so that they know, how best to use the drug and and so forth.
Dr. Moira Gunn:Well, it's it's kind of amazing in one sense. It's like, well, we just talked about this for a few minutes. The PDUFA date's coming up in 4 weeks, at the time of this interview. And this has been a 30 year journey. You just didn't get here now.
Dr. Moira Gunn:I mean, tell us, just just sort of quickly, you know, what what's the what are the bones, the bare bones of that 30 year journey, and what does it feel like now?
Dr. John Scarlett:So I will get to what it feels like now, which I can summarize very simply as saying it feels great. But the 30 year journey is what you often see behind the scenes in highly innovative products. Because you really start out with a hypothesis that a certain mechanism, a certain enzyme to be, targeted, whatever, is is important and and can be targeted, but you don't even have a drug to target it. And so the first thing you really work on usually is getting a drug, and that can take quite a number of years as you go through the process, you know, the chemistry and the biology of, of manufacturing and making a drug that is, is appropriate to interact with the target, in this case, the telomerase target. And then the second then you, once you've done that, you have to do a lot of preclinical, studies to establish appropriate doses and safety and efficacy, and then you go into the clinic.
Dr. John Scarlett:And as you know, Mara, there's usually phase 1, which is first time in man. That's often looking for evidence of activity in different areas that you think might be valuable. Then once you've settled on that, then you have phase 2, which explores dose and the and the way in which you, give the product to patients and establishes the background for proving that your, ideas about how to use use the drug can be proved in what we call usually a double blind and randomized controlled study, which is what is the long name for a phase 3 study, which, establishes the the strength of the data, that regulators can look at and that they can hopefully believe in that allows you then to be approved.
Dr. Moira Gunn:30 years to be an overnight success. I think that
Dr. John Scarlett:That's a good way to put it.
Dr. Moira Gunn:How to phrase that? Doctor John Scarlett is the president and CEO of Geron Corporation. More information is available at geron.com. That's ger0n, geron.com.