Growth hormone deficiency is a rare condition that is the result of inadequate secretion of growth hormone from the pituitary gland. Though recombinant human growth hormone has long been used to treat people with pediatric growth hormone deficiency, it requires either daily or weekly injections and when injections are missed, results can be sub-optimal. Lumos Pharma is developing a once-daily oral therapy that works by promoting secretion of growth hormone. We spoke to Rick Hawkins, chairman and CEO of Lumos Pharma, about the company’s experimental therapy, how it works, and why it may be an attractive alternative to existing approaches.
Daniel Levine: Rick, thanks for joining us.
Richard Hawkins: Well, thank you Danny. It a pleasure to be here.
Daniel Levine: We’re going to talk about pediatric growth hormone deficiency, Lumos Pharma, and its effort to change the way the condition is treated by developing a once-a-day oral therapy. Let’s start with the condition itself. What causes pediatric growth hormone deficiency?
Richard Hawkins: Well, pediatric growth hormone deficiency, or PGHD is a disorder of growth in children and adolescents. And PGHD occurs when the pituitary gland does not produce the normal amount of growth hormone needed for kids to grow taller. So, growth hormone is a key hormone produced in the pituitary gland and supports essential metabolic functions and bone growth among others. And there are a lot of different causes, but it’s usually divided into two categories, either organic, where there’s severe growth hormone deficiency when patients can’t produce any growth hormone at all, or idiopathic growth hormone deficiency where their pituitary access is still functional and they produce some growth hormone, but not quite enough.
Daniel Levine: At what age is it generally diagnosed and how is it diagnosed?
Richard Hawkins: Well, first of all, the incidence is about one in 3,500 children in the U.S. and it can be diagnosed as early as age 2 or 3, but typically patients take a growth hormone treatment, an injectable treatment, for seven to eight years of their lives. But children grow from birth to late adolescence or early adulthood, and depending on the severity of the growth hormone deficiency and the cause, you know, PGHD can be diagnosed in young children as well as adolescents. The phenotype is the fact that that children then end up with short stature, where reduced height compared to their same age peers. And the physicians or families may understand that they have this medical condition fairly early on when at different times they don’t keep up with the growth of their peers, or adolescence when adolescents typically have a growth spurt and that doesn’t happen. So then they get referred to a pediatric endocrinologist. But there are a lot of different ways that you can be referred into the medical system. But these patients are typically eventually referred to a specialist of pediatric endocrinology. Once they get to the pediatric endocrinologist, then they can do certain kinds of lab tests, but also they get an x-ray to check to make sure that their bones or their growth plates or their epiphyses are still open and to see exactly where they are in their growth, or how much more growth they have to go. Then they essentially get referred fairly easily into the system to a pediatric endocrinologist.
Daniel Levine: Beyond being short, what are the effects of the condition and how necessary is it to treat?
Richard Hawkins: Well, the main effect is delayed linear growth or growing taller slower than expected for your age and sex. But in addition to short stature, other effects such as growth failure, delayed puberty can also occur, in other words, other metabolic effects. And because linear growth stops in sort of late adolescence-early adulthood, there’s a limited window of opportunity to treat these patients with PGHD. And so, if treatment is delayed, the child may not achieve their maximum growth potential and be shorter than their adult peers, which ultimately can cause some significant psychosocial distress in many children.
Daniel Levine: One of the earliest products of the biotech industry was recombinant human growth hormone. How effective has this been at treating the condition?
Richard Hawkins: Well, recombinant growth hormone was made available now almost 40 years ago and it is an effective treatment, but it’s burdensome just because you have to take daily injections. And until recently, there’s one company that’s come on the market with a weekly injection, which can be painful and also cause quite a bit of distress in a child. But it also doesn’t restore the natural pulsatile release of growth hormone that our drug does. And I maybe can go into that a little bit later, but even weekly injections, as recombinant growth hormone as an option, arrived on the market only last year. And while these injections really decrease the overall injection burden, it does not eliminate it. But I can just say that the kids just don’t like injections. So, our initial market research supports a very good appetite for an oral therapy versus even a weekly injection. And that was a survey taken of pediatric endocrinologists, but also of families.
Daniel Levine: Lumos’ lead experimental therapy is LUM-201 or ibutamoren. This is not a hormone replacement therapy, but a once-a-day pill that stimulates production of human growth hormone. How does it work?
Richard Hawkins: So, our drug is not a formulation of growth hormone. It’s a small molecule that stimulates production of growth hormone in the pituitary. It’s natural. In other words, it is what we call a growth hormone secretagogue. It acts on a specific—it agonizes a specific receptor in the hypothalamus and the pituitary, and then increases the natural production of growth hormone. In other words, you make your own growth hormone, and we stimulate the further production of it. And that’s important because this feedback loop, this pulsatile release of growth hormone happens naturally 23 to 25 times a day. And all we do is increase the amplitude of each one of those pulsatile releases in a 24 hour period, and so really stays within the natural physiology of a person’s body.
Daniel Levine: Merck was originally developing this. How did Lumos come to develop it?
Richard Hawkins: Well Merck stopped developing it and put it on the shelf. But I can tell you it was designed to do exactly as it was purported to do or show in studies. They initially studied it in about a thousand elderly. And the drug as I said, did exactly as it was supposed to do. It restored growth hormone levels to a late 20 year old, early 30 year old in these elderly folks. And they were studying it for indications such as sarcopenia, or muscle wasting and aging. Essentially the FDA told them that they had no regulatory pathway because these were natural causes and indications, or symptoms of aging. And so therefore they had no regulatory pathway and they put it on the shelf. Their advisor at the time was a renowned endocrinologist, Michael Thorner at University of Virginia. He was also my advisor at the same time when I was developing another drug called Somavert for the opposite problem called acromegaly. And Michael was able to essentially license this drug from Merck and Michael then called me, and that’s when we started on a full development plan.
Daniel Levine: You alluded to the fact that there can be different causes of the growth deficiency. The body in some cases may be unable to produce growth hormone. What percent of patients with pediatric growth hormone deficiency might benefit from this approach?
Richard Hawkins: Well, the range of growth hormone deficiency is quite, you know, as I said, they’re there. Those severe organic patients who don’t make any growth hormones, their access is just not working at all. Those patients should be on recombinant growth hormone. But those patients with moderate growth hormone deficiency still have an intact pituitary that still can make some growth hormone, but they just don’t make enough. Our compound will treat [them]. And that’s essentially about 60 percent of the market.
Daniel Levine: What’s known about ibutamoren from studies that have been conducted today?
Richard Hawkins: Ibutamoren has been thoroughly evaluated by Merck, including extensive toxicology studies in adults and children. Let me start over again, guys. Okay, ibutamoren has been thoroughly evaluated by Merck. They’ve conducted numerous toxicology studies and also in juvenile animals, but they’ve studied in adults and children, and they revealed no safety concerns. And this has been exposed to over 1000 adults and about 300 children.
Daniel Levine: There was interim data from a phase 2 study that compared ibutamoren to recombinant human growth hormone, one factor that suggested the drug didn’t perform as well. What happened and how concerning was the interim analysis?
Richard Hawkins: Well, in the Merck study, Merck included those patients this drug would not work in. They didn’t understand the biology at the time. So, they included those severe organic patients who don’t make any growth hormone and, and a secretagogue compound will not work in that patient population. But when we did a sub-analysis of the data and took those patients out that had severe growth hormone efficiency, the drug showed equivalency to a standard dose of growth hormone, and that’s at 0.8 mg/kg/day.
Daniel Levine: What’s the development path forward?
Richard Hawkins: So, our path clearly was looking at the results of the Merck study and PGHD patients. And we understood that Merck just didn’t give a high enough dose. So, we started with 20 patients and in one arm of a study started with that 0.8 that Merck used, then we doubled it in another arm of 20 patients with 1.6 mg/ kg/day, and then in the third arm, we quadrupled at 3.2 mg/kg/day versus the final arm of 20 patients who took a standard dose of recombinant growth hormone. And the endpoint is height velocity at six months, then annualized. And that’s the design of the study where we released interim results. We were quite pleased with those interim results. In the growth hormone arm there were two patients who were the youngest two patients in the study. And endocrinologists know that the younger the patient, the greater the height velocity. So, there are two outliers in the interim release of the data in November. But clearly, as more patients have been entered, and we’ve just now announced completed enrollment there, there’s been greater balance in those arms, and especially as we stratify by age into the other arms of the study.
Daniel Levine: Recombinant human growth hormone is approved for use of a number of rare conditions beyond pediatric growth hormone deficiency. This includes such things as Turner syndrome and Prader-Willi syndrome, and more. How broadly applicable might ibutamoren be and what’s the plan for pursuing other indications?
Richard Hawkins: Well, Danny, we have engaged the growth hormone community worldwide. And I think we know that we have a chance for a number of indications, but we really, at this point, have narrowed it down to idiopathic short stature or ISF-ISS with a focus on the Asian market because that market is growing so rapidly in that indication. And then also Prader-Willi syndrome. It’s a genetic syndrome characterized in part by poor growth and short stature. And that’s where we’re going to focus next. But I can tell you PGHD and getting the final results from this current study is our complete focus in designing a phase 3 study going forward.
Daniel Levine: Like a lot of biotech stocks, Lumos is down considerably from its high. It’s trading around $3.60 today with a market cap of about $30 million. How far will existing cash take you and what’s the plan for raising additional capital?
Richard Hawkins: Well, we’re obviously an undervalued stock. I mean, we’re trading much below cash, and here we are with an interim result and a phase 2 study and getting ready to release results in the fourth quarter of this year on a full 80 patients on drug for at least six months. We will report final results from this study and a full 80 patients in the fourth quarter of this year. And that allows us to have an enough cash to go into the third quarter of next year. So that gives us plenty of time to not only tabulate these results, but also, we’ve really decided on 1.6 mg/ kg/day as our dose. So, all the advanced planning for that phase t3study is progressing.
Daniel Levine: Rick Hawkins, chairman and CEO of Lumos Pharma. Rick, thanks so much for your time today.
Richard Hawkins: Thank you, Danny. Appreciate your time, too.
This transcript has been edited for clarity and readability.
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