Growth Hormone Deficiency Learning Zone
Transcript: Comparing treatment options in children
Professor Mehul Dattani, Dr. Charlotte Höybye, Professor Steven Simoens, Dr. Shankar Kanumakala and Dr. Robert Murray
Interview recorded Jul 2023. All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
So thank you very much, Rob. Dr. Shankar, over to you for the next one. So if I just forward the slide. And this is obviously now "Comparing growth hormone deficiency treatment options" in the light of the introduction of long-acting GH in children. So thank you, Shankar. Thank you, Mehul. And thank you Medthority for this very important growth hormone deficiency treatment roundtable discussion. These are my disclosures. And when we come to the treatment options with growth hormone therapy, one treatment option is completely closed because as we all know, human growth hormone is a large protein molecule and cannot be taken orally. So growth hormone has to be administered parenterally via injections or transjections. And when we look back over the decades, there has been numerous advances with growth hormone therapy. And looking ahead, we are all sure that many more advances are likely to come in the years to come. But the pivotal point perhaps was the mid-'80s, when extracted growth hormone from cadaver pituitary glands was discontinued, and first biosynthetic growth hormone became available.
And since then, various other biosynthetic preparations followed. The first biosimilar growth hormone was licenced in 2006. And as we know, the long-acting growth hormone analogue therapy with weekly injections, was licenced in 2022. And when we come to the daily injections, we have in the daily injections or the somatropin, which is given as a subcutaneous injection. And looking backwards, the alternate day regimen, and intramuscular injections of growth hormone preparations were also discontinued in the '80s. And now we have several biosynthetic preparations of somatropin, and one biosimilar preparation. And there are many options here with the devices. We do have pen-filled cartridges, we have pre pen-filled prepared pens, we have needle cover, we have autoinsertion of the needle, and we also have single-use disposable devices with the preparations. And all these things will improve the what is that availability and options for treatment, based upon personal choices, personal preferences, and what is that in some instances, what is that unique characteristics of the patient. Like for example, if a patient has got such severe needle phobia, a needle cover would be really helpful in order to disguise the needle. Or when they have tremors, autoinsertion of the needle will be really helpful.
Now going forward, the weekly injection or long-acting growth hormone preparations, namely somatrogon and what is that, lonapegsomatropin, came into the market and became licenced in 2022. But what is important for all of us to remember is, over the years, many long-acting growth hormone preparations have been withdrawn, and many long-acting growth hormone preparations are still in various stages of clinical trials. The weekly or the long-acting preparations have some benefits over the daily injections, and this is to do with the treatment burden. The daily injections, as we know is daily, and in the mid-'80s, the weekly or alternate day injections and various other regimens have been shown to be less effective and has gone out. And now the daily injections versus weekly, once a week injection, will definitely improve the treatment burden for the child and the family. Now will this also, what is that improve the adherence? The short term study shows yes, it will improve adherence. But is it the real world longer term practise is a matter to be, what is that, established? And many patients in the clinical trials have preferred the weekly growth hormone injections, rather than the daily growth hormone injections. And these weekly injections are shown to be equally efficacious and equally safety in phase 3 trials.
When we look at somatrogon, it has shown the annualised height velocity of 10.1 centimetres versus 9.8 centimetres per year, is non-inferior to daily somatropin treatment after 12 months of treatment. With the other licenced long-acting growth hormone preparation, namely lonapegsomatropin, the annualised high velocity in this cohort study showed not only a non-inferior outcome, but also statistically significant outcome of 11.2 centimetres versus 10.3 centimetres in the daily somatropin use. Now it is hypothesised by these authors that the regular use of the somatropin, by the long-acting lonapegsomatropin, is superior or is much more physiological rather than the daily injections where it is only released once a day. Obviously it needs to be proved and obviously it needs to be in the longer-acting, whatever in the long term studies. When we come to the safety profile, it is comparable.
But the two studies does show that there is some differences. And in the somatrogon study, there is some increased whatever complaints regarding injection site erythema, pain, pruritis with somatrogon, whereas more headaches was recorded with somatropin. With the lonapegsomatropin study, there was slightly, not significant, but slightly high serious adverse events in the somatrogon patients, as compared to the somatropin patients. But the longer term data and also the real world evidence in years to come, will hopefully settle this question. But in the short term, the practical questions still remain and they are, "what is the method of dose adjustments?" And in both these studies, a standard dose was used. And in order to achieve individual optimised height outcomes, how do you really adjust these what is that doses for these patients? And that is an important practical question. And another important practical question I think is, what is the timing of monitoring IGF levels and its influence in the long-acting growth hormone preparations and its dose adjustments? So everything is not, within inverted commas, hunky dory going forward But we do have important, what is that, progress in this area. But finally what I want to say is growth hormone therapy has come through forward in bounds and leaps, but there are still questions that needs to be answered. And one of the thing is, which my colleagues will tell about the real life is, it is only effective when it is given. And we do know that what is that treatment adherence, is going to be one of the important factors for good patient outcomes with growth hormone therapy. I think I'll stop there and open up for discussion and guidance from the team. So I think in the UK at the minute we only have somatrogon, don't we?
Rather than the lonapegsomatropin. And also the REAL 4 study, which was somapacitan, showed benefits similar to the other two products. But I can't see that that's been licenced or hasn't been advanced, so- No. Do you know why there's a difference in these products getting to the UK market or to the European markets? I'm afraid that I don't know the reasons why it is not coming into the UK market. But I do know that the other product is still in its early stages and it has not received, what is that, approvals from either EMA or FDA. But probably we might see that one in the near future. These products. Do you feel they will be accepted into the market for adults just based on adherence? Or in adults, will we expect the adults to take their once daily rather than pay more for a product that might be increased adherence? I mean, I believe, what is that, there is a role for the weekly growth hormone. And that at this point in time, it is thought to be the adherence.
However more whatever things will come to light in the years to come, as our experience with it improves. Now the lonapegsomatropon suggests to be, that it is slightly more superior than daily growth hormone therapy because of the way it is regularly and continuously released into the system. And when we are thinking about, what is that getting the best outcomes for the patient, the importance is both signs on the one side, but also the patient choices or patient preferences on the other side. So here we do have a trade off. Whatever you do, you have to take the growth hormone, and what will be the one that you will be willing to take? Yeah, I think, sorry, one's got to be a little bit careful of sort of saying that one's better than the other. I mean, I think at the moment it's comparable efficacy is what I would say. Correct. The costs I gather they're trying to keep as similar as they can to their daily product.
Yeah. And obviously we are talking more about somatrogon in UK and Europe. Yeah. But you're right, Shankar. I mean, I think we are finding our way around it, and I think what would be a sensible approach I guess, is to try it in things that you are more familiar with, like isolated GHD. Absolutely. And you know, maybe even hypo-pit, but again the dose you've got to be careful, certainly in severe GHD. Because these children are very, very sensitive to low doses of growth hormone. Yeah. I never start with high doses. I start with very low doses and then build up according to the IGF-1. Yeah. And I think, you know, my personal feeling is this was going to be useful in selected groups of patients where adherence is a problem. Yeah. The other groups are children with learning difficulties or autism, where, you know, it may be much easier.
Yeah, I mean when you come to the children with learning difficulties or whatever it is, some children can be really, really troublesome, where giving an injection is going to be a daily hurdle for the child, and the family, and the carers. Whereas a weekly injection would be much, much better and kinder. Having said that, when some children with autism, after a period of time become, what is that, used to this new routine, and then they will accept it. But what is that to start off with giving them a lower treatment burden would be kinder and more appropriate. And I completely agree with that point. Yeah, yeah. I mean, do you think, Rob, that in adults that there will be a role for this in due course, and that there will be an update? I worry about the adult side of things 'cause it really is adherence and you're just thinking a health system with finite resources, that if the funding is different and it's slightly more expensive, then the funding which is essentially the government is going to say, "Adults should be able to take this on a daily basis." So unless the costs are fairly equivocal, I suspect given that we don't have something as important as growth, that we'll have more trouble getting this product to market, to be able to use it. Yeah, yeah.
You were saying something, sorry. Yes, I would like to say also for the adults at least, but maybe also for the children because of the different pharmacological capacities of these weekly injections. There's also a different pattern of, we're so used to looking at IGF-1 as a marker and it's the 24 hours variations. But with these weekly products, we have a different relationship between growth hormone concentration and IGF-1 concentration. Maybe it will have, it will play a role in the long run for the development of diabetes or not, or for neoplasm, we don't know. Correct. Absolutely. And because of the different pharmacological... Pharmacology of these products, we also need to use a higher dose of them. The dose need to cover the whole week. Yeah, I think we need to find our way. I think I'd better wrap the session up then. So, thank you very much. Thank you, Mehul. Shankar, it's good discussion.
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