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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.
The world we know is changing. I'm Moira Gunn, and welcome to Biotech Nation. Over time, we may develop conditions where we either stop producing hormones or produce less than we need, or alternatively overproduce hormones. Today, we'll look at the French company, AMOLED Pharma. It's developing a number of hormone correcting treatments, and we'll talk about 2.
Dr. Moira Gunn:One condition is caused when the parathyroid, that tiny gland behind the thyroid, is injured or removed. We'll also talk about a second condition called acromegaly when the pituitary gland overproduces growth hormone causing abnormal and visible growth in the hands, feet, and face. Doctor Mark Sumeray is the chief medical officer of AMOLYT Pharma. I was able to speak with him from AMOLYT's offices in Cambridge, Massachusetts. Well, doctor Summeray, welcome to the program.
Dr. Mark Sumeray:Thank you very much. Pleasure. Thank you for the opportunity.
Dr. Moira Gunn:Now, everybody has a thyroid.
Dr. Mark Sumeray:Mhmm.
Dr. Moira Gunn:What could go wrong?
Dr. Mark Sumeray:Well, most of the time, nothing. But occasionally, there's a variety of things that can happen with the thyroid gland that mean that the gland may need to be removed. For example, you can develop, cancer or tumor in the gland, or you can have cells in the glands that are overactive and producing too much of the hormone that is produced by the thyroid gland, thyroxine, or or not enough. In which case, you have to have, replacement, tablets to make up for the missing hormone. So there's a variety of things that can happen.
Dr. Moira Gunn:Now from our earlier conversation, I also learned that you don't just have a thyroid, you also have a parathyroid. What does that do?
Dr. Mark Sumeray:Yes. So those glands are immediately behind the thyroid gland in the neck. And they're important because they produce another hormone called parathyroid hormone, which regulates primarily the amount of calcium you have in your bloodstream. So it's very important to make sure that the levels of calcium don't go too high or too low.
Dr. Moira Gunn:Don't they usually say calcium, you know, strong bones, good teeth? Isn't that the isn't that the message from the milk people?
Dr. Mark Sumeray:Yes. That's true. So you you don't want to have too little calcium and and having too little calcium in your diet can cause problems. But you also don't want to have too much in circulating in the blood. So these glands are important for keeping the calcium exactly where it should be.
Dr. Moira Gunn:So it's not the calcium, but it's what helps the calcium be in the right proportion.
Dr. Mark Sumeray:Exactly. It's producing the hormone that the body needs to regulate the calcium levels.
Dr. Moira Gunn:So when you have thyroid surgery as an example, does that involve the parathyroid?
Dr. Mark Sumeray:Well, it shouldn't because, usually, the surgeon is trying to remove the thyroid gland and that gland alone. But because the parathyroid glands are very small and they can be difficult to see at the time of the surgery, and they're often very very closely caught up in the thyroid gland. They can be removed at the same time inadvertently, or simply because the surgeon isn't able to remove the thyroid gland without removing the parathyroid glands as well.
Dr. Moira Gunn:And could the parathyroid simply be not operating correctly?
Dr. Mark Sumeray:So it's not usually the case. What happens is that the surgeon has removed the thyroid gland usually because of a cancer or because the gland is simply too big and it's causing problems because of its size. And when the thyroid gland has been removed, the parathyroids are damaged or removed as well. And it was something that the surgeon wasn't able to avoid doing. So then what happens after the surgery is a result of having inadvertently removed the parathyroid glands and then caused a problem because now the patient's parathyroid hormone levels are too low.
Dr. Mark Sumeray:So, it's a if you like, an unintended consequence of the surgery on the thyroid gland.
Dr. Moira Gunn:How often does this happen? How many people are affected?
Dr. Mark Sumeray:Well, fortunately, it doesn't happen very often. But even in the most experienced surgeon's hands, we can say maybe between 1 3% of cases. So it just, although it doesn't happen very often, even with the most experienced surgeons, it's sometimes unavoidable.
Dr. Moira Gunn:What is it like if for any reason you lose your parathyroid gland?
Dr. Mark Sumeray:Well, in the beginning, so once the thyroid gland has been removed and this is the most common scenario, the patients are monitored very carefully to see if they have adequate parathyroid glands, left behind. And it's not apparent whether or not that's happened, until usually 6 months after the surgery. So the patient's calcium levels are monitored very carefully. And often, the parathyroid gland, function will recover because usually there's some gland that's still been left after the surgery. But if, after 6 months, the patient is still needing calcium supplements because the parathyroid hormone levels are too low, that's usually when the diagnosis is made.
Dr. Mark Sumeray:And, that's when, certainly after a year nowadays, the conventional, time point for the diagnosis to be formally made, that's when that happens. So if there's no recovery of the parathyroid, glands a year after surgery, then the patient is formally considered to have hypoparathyroidism, which is the the medical term for low parathyroid hormone levels.
Dr. Moira Gunn:How many people are affected by this?
Dr. Mark Sumeray:So in the United States, approximately 70,000 people are thought to have hypoparathyroidism. And those people, when they're diagnosed, they have a disease which is something that will stay with them unfortunately for the rest of their life because we, you know, we can't, replace the the glands. So what we have to do is manage the consequences. And those consequences are a result of not enough parathyroid hormone which leads to low levels of calcium in the blood. So these patients suffer symptoms of hypoparathyroidism that can be extremely debilitating.
Dr. Mark Sumeray:They can have symptoms caused by muscle cramps, muscle spasms, strange, tingling and numbness sensations that affect the the skin. They often find it very difficult to concentrate on routine everyday tasks. They have a condition which is called brain fog, which is a very, you know, descriptive term for, how they feel. And, they it really interferes with the quality of life. And the problem is that the only way that they can manage these symptoms is by taking large quantities of calcium tablets and vitamin d, which helps with the absorption of those calcium tablets.
Dr. Mark Sumeray:And as a result, they have to walk around everywhere with a supply of calcium tablets in a ziplock ziplock bag. And it's it's something that really dominates their lives. And, of course, the other problem is that they can manage the symptoms to some extent with these calcium tablets. But at night, of course, when you're asleep, you know, you get, you can't remember to take calcium tablets as soon as you start to feel symptoms. So they often will wake up with these symptoms, and it causes a lot of, as you can imagine, distress and debilitation.
Dr. Mark Sumeray:And many of these patients end up, you know, becoming quite depressed about the, the condition that they have.
Dr. Moira Gunn:What are the long term effects on the body of having this condition?
Dr. Mark Sumeray:So in addition to the symptoms that I described, the effects on the body are caused by deposition of calcium, salts in some of the tissues in the body over the years. And also the damaging effects of having too much calcium in the urine because in this disease, because they don't have the hormone, the kidneys are not able to reabsorb calcium normally. So the calcium that they do have in the blood ends up leaking in high quantities into the urine and that causes kidney, damage caused by kidney stones and, a deposition of calcium in the tissue of the kidney. So long term, there are multiple consequences and the kidney is certainly one of the organs that's affected.
Dr. Moira Gunn:Well, why not just give them the hormone?
Dr. Mark Sumeray:We'd like to do that, but unfortunately, we have to inject the hormone. And when we inject it, it has a very short duration of action because it has a a short residence time in in the blood and in the body. So after 45 minutes, half of it's gone completely from the bloodstream, and the effect only lasts really for an hour or 2. So constantly giving injections of this hormone isn't really an option. We need to find an alternative.
Dr. Moira Gunn:Now this is what AMOLED is working on. What are you doing?
Dr. Mark Sumeray:So we've taken, an approach which involves modifying the hormone so that we have something we can inject which has a very long duration of action even though it has a short residence time in the blood. So, the the the drug that we have, which is called enebaparatide, is specifically designed to bind to the same target as the natural hormone, but its activity lasts a lot longer. So after a single injection, we still see the action of the drug on the calcium levels 24 hours later.
Dr. Moira Gunn:Doctor Mark Summeray is the chief medical officer of AMOLED Pharma. AMOLED's focus is on rare endocrine and related diseases. We've just been talking about their drug candidate to continuously replace the hormone which processes calcium in the body. It requires a daily injection. Now when you give someone an injection, it it covers their whole body.
Dr. Mark Sumeray:Mhmm.
Dr. Moira Gunn:Does it do different things in different places?
Dr. Mark Sumeray:So the the the drug binds specifically to the receptors that we have, that are there because of the natural hormone. So it's binding to the same receptors and it is present in different tissues in the body. But this drug effect is really focused in the kidney and the bone, Where in the kidney, it stimulates the reabsorption of calcium so that patients no longer have the problem with excessive amounts of calcium in the urine. And in the bone, it stimulates, the bone to turn so called turnover, which means that we break down old bone and replace it with new bone, which is something that in normal healthy situation happens all the time. So in patients with this condition, because they lack the hormone, the bone goes to sleep.
Dr. Mark Sumeray:It becomes dormant. So the old bone accumulates and is not broken down and replaced by new healthy bone. When we treat them with an with our drug, what we see is the reawakening of the bone, and the bone starts to turn over again. An old bone is broken down and new bone is made to replace it. So the actions of the drug are largely focused, in the kidney where we see the reabsorption of calcium and in the bone where we see a restoration of normal balanced turnover of bone.
Dr. Moira Gunn:So without a medication such as this, over time your bones are gonna be in terrible shape.
Dr. Mark Sumeray:Well, so it's a bit controversial in the disease whether or not patients have who have hyperparathyroidism have a higher risk of bone fracture. That's the thing we are concerned about. We do know that this old bone, situation, is not normal. So we we know that the structure of the bone is not as it should be. It's not healthy.
Dr. Mark Sumeray:What we're not sure about because we don't have enough patients with this disease followed for long enough is what incidence of increased risk of fracture that represents. However, we know it's not a normal healthy situation. And one of the main problems actually with the bone in this condition is that many of the patients with this disease are postmenopausal women. And the reason for that is that postmenopausal women are more frequently have thyroid cancer than other demographics. And postmenopausal women as everyone generally is aware tends to have bone loss over time because of the absence of estrogen.
Dr. Mark Sumeray:So they're at more risk of bone fracture. So one of the most important components of managing this condition is to replace the function of the hormone, parathyroid hormone, with a treatment that does not cause bone loss. And in other words, to keep the calcium levels in the blood in the normal range, but not to do it by withdrawing the calcium from bone at the expense of causing, a loss of bone mass because particularly in peri or postmenopausal women that could increase the risk of bone fracture beyond what they already have.
Dr. Moira Gunn:What was so interesting to me about what you said is so many times we say we just wanna fix this, and you're like, wait a minute. We have a complex situation here. We wanna make sure all of these things return to balance, none at the expense of another.
Dr. Mark Sumeray:Yes. Exactly. And it's very important that we don't solve one problem and then create another one. And in particular, the bone situation for a sizable subgroup of patients with this disease is one that needs special attention because of the the, the fact that post peri or postmenopausal women are increased risk of bone fracture. So we we mustn't make that situation worse, in solving the problem they have with the calcium levels in the blood.
Dr. Moira Gunn:Now you're currently in a phase 3 trial, the last phase of clinical testing.
Dr. Mark Sumeray:Mhmm.
Dr. Moira Gunn:Tell us about it. What is it like for someone in it? Where are you testing in the world? And, can people still join this trial?
Dr. Mark Sumeray:Yes. So we have sites in hospital centers in various countries around the world including, several sites in the United States as well as in Europe and Australia, Canada. So the study has just started as you as you said. It's open to patients who have hypoparathyroidism. And generally speaking, it's a fairly straightforward set of criteria that one has to satisfy to be eligible.
Dr. Mark Sumeray:So most patients with hyperparathyroidism will be able to participate. And it involves being randomly allocated either to our drug or to a placebo, and then being very closely monitored for 6 months on treatment. And during that 6 month period, the calcium levels in the blood will be evaluated. And the supplements that patients take, those calcium tablets and the vitamin d tablets that they take, will be gradually withdrawn in a careful way. And obviously, those patients who are randomized to the drug, one would expect to be successfully withdrawn from the supplements and to maintain calcium in the desired normal range.
Dr. Mark Sumeray:And those that are on placebo will have to stay on the supplement. So they they'll start to be withdrawn and then they'll have to be reinstated. So that's really the evaluation is how many times, how many patients are able to come off supplements and still have normal calcium levels. The other important thing to know about the study is that the random allocation is 2 to 1. So that means that for every patient who enters the study, they have a 2 in 3 chance of being random randomized to receive the drug and a 1 in 3 chance randomized to placebo.
Dr. Mark Sumeray:But then after the 6 month evaluation period, all patients will be on the drug. So those that were on the placebo will be moved across if you like to, receive the drug, and then there's another, 6 month treatment period on the drug. And actually probably beyond that, all the patients will probably stay on the treatment ultimately until hopefully we get the drug approved.
Dr. Moira Gunn:Now is this self injection?
Dr. Mark Sumeray:Yes. It is. Now obviously we provide some assistance so that patients can learn how to do that and maybe unfamiliar obviously to many people but we make it very easy. So user friendly because we provide a pen device, which has the drug in a solution, in a cartridge within the pen. It's very easy to dial the the dose that is needed.
Dr. Mark Sumeray:So the dose of the drug may change during the course of the evaluation depending on each patient's response. But it's easy to adjust and the physicians who are taking care of the patients in the study provide those instructions based on what happens to the calcium levels in the blood. So each patient will be instructed on how to use the pen. It's very much like, the kind of pen device with a very fine needle that is used by people with diabetes every day. So it's, it shouldn't be, too concerning.
Dr. Mark Sumeray:It should be quite straightforward, for patients to manage.
Dr. Moira Gunn:And this would be once a day, sort of at the same time every day
Dr. Mark Sumeray:Yes.
Dr. Moira Gunn:Approximately?
Dr. Mark Sumeray:Exactly. Yeah. Once a day. And, yes, it's you know, it shouldn't be a problem for for patients and once they get used to doing it, I'm sure, you know, for most people, it's not it's not daunting at all even though it may sound a little bit daunting at the beginning.
Dr. Moira Gunn:Brush your teeth. Give yourself an injection. Very simple. Okay. So I've got a routine a routine here.
Dr. Moira Gunn:Now you've been talking about measuring calcium in the blood. Do you go forward to see a differential in their bone at all?
Dr. Mark Sumeray:Yes. So we we want to monitor what happens to the bone. So as I mentioned before, we expect to see a resumption, a return of bone turnover. So we start to see something that's much more normal or physiological. And we expect that that will translate over the longer term into a stable situation, which is more healthy for patients where they are replacing old bone with new bone, and they're not losing or creating bone over time.
Dr. Mark Sumeray:They're in an equilibrium or a balance. So we're going to do some imaging tests, which are noninvasive and very straightforward for patients to have, based on a special type of x-ray, which will tell us about the total bone mass that that, patients have over time on treatment. So we can see what's happening to the the amount of bone that they have, the density of the bone, and also the quality of the bone to some extent.
Dr. Moira Gunn:Now how do they find out about joining this trial?
Dr. Mark Sumeray:So this is something that they can talk to their own physician about. So patients with hyperparathyroidism will be managed by an endocrinologist. And it's something that the endocrinologist can look into. So some of the patients may in fact already be seen by an endocrinologist that is participating in the study. Other patients may not be, but even in those cases, they can talk to their endocrinologist about that they're aware of the study and the endocrinologist can make the contact for the patient with whichever is the closest, most convenient participating site.
Dr. Moira Gunn:Now I have to tell people that AMOLED is working on a number of conditions, and, there's one that I want to talk about. It's early. It's it's in humans. It's phase 1, but it's another condition which has a a hormone issue. And that's a condition in which you have too much growth hormone.
Dr. Moira Gunn:Tell us about that.
Dr. Mark Sumeray:Yes. So this condition is called acromegaly. It's also a fairly unusual rare, disease. And as you said, it it's caused by high levels of growth hormone that are being produced by a benign tumor. So not a malignant cancer, but a group of cells in the pituitary gland, which is at the base of the brain that are overproducing growth hormone.
Dr. Mark Sumeray:And this causes all sorts of problems over time. It sometimes happens in childhood. But when it happens in adulthood, unfortunately, it's a diagnosis that can sometimes be missed for a long time because these symptoms happen very slowly over time and they're a bit they these symptoms are, not necessarily specific. They don't make the doctor think about acromegaly in the beginning. But the condition is one that needs to be treated.
Dr. Mark Sumeray:And, because it causes symptoms, but also longer term complications like diabetes and cardiovascular diseases, So it's a a serious condition that if it's not treated will lead to long term, organ damage and and and it also negatively impacts patients' quality of life quite substantially. So it causes, joint pains, joint swelling, causes blood pressure to be raised. It causes, tiredness, less, difficulty, low energy, difficulty concentrating. It causes symptoms related to the complications like diabetes and those kinds of
Dr. Moira Gunn:It's like Joe, Joe, you're just getting old. Get used to it.
Dr. Mark Sumeray:It turns
Dr. Moira Gunn:out. It is something. Yeah.
Dr. Mark Sumeray:Yeah. It ends. So these symptoms are rather nonspecific, but they're quite debilitating. And as a result, until a doctor thinks of the possibility, unless they recognize the physical signs, which can be quite subtle, but to an experienced physician, an endocrinologist, they immediately recognize them. Sometimes the diagnosis is missed, but these physical signs include usually facial features that become coarser.
Dr. Mark Sumeray:The jaw becomes a bit bigger. The brows become more prominent. The, the joints become swollen. These these kinds of physical changes, are typical of acromegaly and would be recognized by somebody that sees acromegaly patients, but may be missed by a doctor that doesn't.
Dr. Moira Gunn:Is there a test for it? A medical test?
Dr. Mark Sumeray:Yes. You can measure, growth hormone levels, or a related hormone called IGF 1, which is produced by the liver in response to growth hormone. These are diagnostic, that laboratory tests you can do on the blood.
Dr. Moira Gunn:Well, doctor summary, I have to say there's a lot of interesting things going on at AMOLED Pharma.
Dr. Mark Sumeray:Yes.
Dr. Moira Gunn:You don't take any of the easy ones, do you?
Dr. Mark Sumeray:No. Well, the company is focused on rare hormonal diseases. And, we have expertise in the company that is particularly applicable to these kinds of conditions because people who work at AMOLED have a lot of experience both in terms of the chemistry and the design of the the, the protein, the short protein molecules that we that are our drugs and the development of them once they get out of testing in the lab and into the clinic. So, it's a group of people who've all worked in the field for quite a long time. And, of course, we will benefit, from each other's expertise.
Dr. Mark Sumeray:And hopefully, we we can move some new drugs through development and get them approved so that they're available for patients to to benefit from.
Dr. Moira Gunn:Well, doctor Summer, I thank you so much for joining me, and I hope you'll come back and see us again.
Dr. Mark Sumeray:It's been a pleasure. I hope so too. Many thanks.
Dr. Moira Gunn:Doctor Mark Sumeray is the chief medical officer of AMOLYT Pharma, a French company with additional offices in Cambridge, Massachusetts. More information is available at AMOLYT Pharma dot com. That's amolyt, amolyt. Amolyt. Amolytpharma.com.
Dr. Moira Gunn:Listen to more biotech podcasts at biotechnology.com or subscribe on your favorite podcast provider. Bio Tech Nation is a regular feature of the weekly public radio program, Tech Nation. Listen to the full show via podcast or on your local public radio station. For Bio Tech Nation, I'm Moira Gunn.