Transcript
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You’re listening to GLC on ReachMD. This activity, titled, Conference Coverage at ICCBH 2026: From Achondroplasia Presentation to Practice,is provided by Global Learning Collaborative.
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Dr. Hoover-Fong:
Hello, and welcome. I'm Julie Hoover-Fong.
Dr. Savarirayan:
Hello, and I'm Dr. Ravi.
Dr. Hoover-Fong:
Ravi, it's really great to be having this conversation with you. The treatment landscape for our patients with achondroplasia is evolving really rapidly. And at ICCBH 2026 we had new important data that were presented here, and clinicians are eager to understand it. So to start with this conversation, can you briefly put the current treatment landscape into perspective and explain why these new data generated so much interest?
Dr. Savarirayan:
Yeah, thanks, Julie. Great to be with you today. And as you know, for so many years people living with achondroplasia had really no therapeutic landscape, because there was no treatment that addressed the underlying physiology, and over the last decade, you and I have seen a real explosion in options for families with a real increased focus on modifying the condition in terms of patient outcomes, and we're getting further there. And what happened at ICCBH yesterday was just another step in the direction to better health outcomes and treatments for families, which is super exciting.
Dr. Hoover-Fong:
One of the most anticipated presentations for ICCBH this year was the PROPEL 3 study. So for clinicians who might not have been able to be at the presentation, what are the most important findings from the data that you could share?
Dr. Savarirayan:
Yeah, thanks, Julie, and it's great, everyone's getting it from the horse's mouth, because you and I are the first and second authors of the paper, which is great.
But basically, the study was a gold standard, double-blinded, randomized, controlled design in children with achondroplasia all of whom had been in an observational study for 6 months to establish their baseline characteristics, not just growth but also proportionality and other issues that they were having, and then they were randomized 2:1 to either a medicine called infigratinib, which is an oral molecule that inhibits the FGFR3 receptor, or placebo, and basically they were all followed for 52 weeks.
And we've just had the headline results, which show that there was a significant increase in growth and improvements in body proportionality in treated versus untreated children and, very importantly, the safety profile of children given the medication versus the children given the placebo was very similar.
So another step forward in the therapeutic landscape, so super exciting.
Dr. Hoover-Fong:
So beyond the efficacy and the safety results that you were just talking about, what findings stood out most to you as particularly important from the results from the study?
Dr. Savarirayan:
So we know achondroplasia should never be thought of as just a short-statured condition. It's a condition in which there are many complications, and some of those are due to the disproportionality. Children who have shorter legs and shorter arms, which means they can't be as functionally independent and reach things. And so what the study has shown was not only was there a good efficacy effect in terms of height, but we also had a good effect in terms of proportionality.
In the subgroup of patients aged 3 to 8, we saw a significant improvement in the upper-to-lower body segment ratio, which is a kind of indication that the legs are growing and people are becoming more like average children in their proportionality, which we hope will translate into better functionality. And we saw the same thing with arm span, because we want to make sure that the arms are growing with the trunk and the legs and everything appeared to be growing in a more proportional manner. And we hope that this will allow children to be more functionally independent, have better quality of life, and actually do more. And obviously it's not game over, because we're following all these children now until they finish growing, and we can assess these things directly.
Dr. Hoover-Fong:
Well, the follow-up is so important.
Dr. Savarirayan:
Absolutely, yes.
Dr. Hoover-Fong:
If a clinician remembers just one thing from the results of the PROPEL 3 study, what should it be?
Dr. Savarirayan:
We would like clinicians to know, firstly, that there are new treatments for children with achondroplasia, and one promising treatment in development is an oral therapy that is looking very, very promising and may be approved. So it's important to know it may be available soon. But we have better therapeutic options for children than just waiting. That's the key message. People need to know it does exist.
Dr. Hoover-Fong:
So clinical trials can be statistically significant, which is nice for publications, but families want to know if that really means something in everyday life. So how should clinicians interpret, again, some of those results or the magnitude of some of the benefit from PROPEL 3 into their patients?
Dr. Savarirayan:
Yeah. Great question. I think even though it’s the phase 3 trial and it's published, it's just the first step. What we need to do is now translate our study endpoints into meaningful patient outcomes. I'm always saying to people, never confuse the primary endpoint of a study, which is a regulatory thing, with the purpose of treatment, which is better health for our patients.
So it's really important that we set expectations, and we say yes, this is an important step, but what we want is these changes in height and proportionality to translate into increased functionality, decreased medical complications, and we need to really redefine response as health. It's not just height as our response, and that's really going to be important for the medical community to get their heads around, because that's what families want: 1.74 centimeters in a vacuum means nothing. But if that means a child can now be more independent and reach things and do more things like toileting and getting onto a bus more independently, that's important.
Dr. Hoover-Fong:
Agreed. So what gives you the confidence that the study findings actually could change actual practice, day-to-day practice for our patients with achondroplasia? And then what's still unknown about the results for using this treatment?
Dr. Savarirayan:
Yeah, I think the strength is the strength of our study, the gold standard randomized controlled trial, and I think the fact that it was published in TheNew England Journal of Medicine is a big thing, because they take the best evidence that will be changing practice. And so we've got to now follow up on that with following all these children to make sure we realize that that effect is not just 1 year but 2 years, and then final adult height, and how that then translates into all the health outcomes I talked to as well.
Although we're quite confident with the safety, we need to keep monitoring to make sure that there are no safety signals that come out down the track. So that's really important.
But most important for me would be making sure we translate those endpoints to meaningful health outcomes for families. And they've really been set by families, so we really need to be guided by what our patients ask us, and that's where it's lucky, because you and I spend our whole lives with patients, so we get to hear the unfiltered voice.
Dr. Hoover-Fong:
Yeah. It's beyond height.
Dr. Savarirayan:
It is beyond height. Amen.
So, Julie, I'm going to turn interviewer to you now. So we are arriving at a time, as we've discussed, when the therapeutic landscape is changing, and really quickly, can you talk us through a little bit of how these particular results fit into the broader picture we're seeing in achondroplasia?
Dr. Hoover-Fong:
Sure, it's just an exciting time that you actually have choices now for your patients and have that discussion. There are differences between what is out there, and it's very important for people to understand those things. The big differences of modulating the FGFR3 function through C natriuretic peptide, but now we have this where we're hitting the base of the whole abnormal function at FGFR3 with this new drug.
And it's exciting, and we are set up so that we can watch for the long-term benefits. We just said it's beyond height. It is so much beyond height. And in addition to the safety, we want to make sure that that sustained additional growth that we have goes on and on and that we see the changes in function over time. And we're at a really exciting place where we're starting to see maybe some of those secondary problems that need surgeries later, maybe we're going to be able to avoid that.
So all of that together is just a tremendous accomplishment and really exciting for our families.
Dr. Savarirayan:
And I guess the other thing that's been that step forward is there's no currently approved therapy that's an oral medication. Currently, they're all injectables, and for young children, oral is a nice way if we can show the effectiveness.
Dr. Hoover-Fong:
If a family chooses to take on one of these medications, that is huge. You and I are both in the clinic with the young kids, and taking an oral medication over an injection is definitely a plus.
Dr. Savarirayan:
And this feeds perfectly into the next question: What do you think will be the most important outcomes when families are trying to compare and contrast treatments?
Dr. Hoover-Fong:
It is an individual decision. We both have these conversations with people. There are some families that are completely focused on the height part of the potential benefit, but all of the functional differences that could come from that. Particularly, you mentioned the arm span earlier. That's huge. That's really huge. Those are things that could potentially change someone being able to drive without having to be so close to the steering wheel, for example. That's a big quality of life potential.
Hopefully these potential opportunities from these medications can really meet the needs that the families feel like they have for their children. And I just think it's exceptionally important that it's a shared decision-making process as we figure out with the family what the best route is for them to go, and duration of treatment too.
Dr. Savarirayan:
Absolutely. I mean, you and I have spoken about the fact this is not a 5-minute conversation with a family anymore, because in the past it was, “We don't have any treatment. Bye bye.” Now there are many different treatments, and it is a complicated discussion because families need to make informed choices.
Dr. Hoover-Fong:
Yep. Agreed.
Dr. Savarirayan:
So, Julie, there's a lot of information out there for families. How do you help families decide which one of these therapeutic options they might want to take when you're having a conversation, say, with a new 4-year-old and their parents?
Dr. Hoover-Fong:
It's a tricky question, and it's a question that happens every day as we're seeing these patients. I think it's exceptionally important to explain to families that there are options, and it's a matter of meeting them where they are. So those scenarios, you said a 4-year-old, that's a different prospect than a newborn and also a different prospect than a 10-year-old. So a 4-year-old has that ability to talk back and maybe not be so thrilled about the options of an injection medication versus an oral medication, which is kind of what we're talking about today.
But a tradeoff that's really important to go through with the family is that we have a lot of longitudinal data for some of the medications that have been around a little bit longer. And when a family is really wanting to know are we getting a response? Do we expect that this is going to work? That's an important consideration. We have lots of data on that.
Now, having said that, I know you do the same thing. We're talking with these families that we're following over time. We're going to keep revisiting that every time they come in. Is their child responsive to that medication, whatever they choose? If they choose to use treatment like that, are they responsive to it? And then we're making that decision: do we keep going further, or do we need to reassess and see if something else is an option? Now we have options. It's kind of amazing.
And I think the other thing for the longitudinal care with the family, I know you will agree with me on this, is that the treatment of monitoring for obstructive sleep apnea, the hearing issues, all of that still happens. It doesn't matter what medication you may pick, or no medication at all, you still need to come to clinic. We still need to see you for that longitudinal follow-up.
Dr. Savarirayan:
Absolutely, I agree with everything, and the only thing I would add is we have to individualize the conversation to every family. We can't just do a standard talk and give it to everyone. It depends on the age of the family, the expectations of the family. It may be very different if the family is from a family where there are many people with achondroplasia or it's a new family. All of these things change.
And the other thing to remember, there's some practical considerations. If we're talking to a 1-year-old in my country or the US, there's only one medication available.
So we have to be very practical, and then we have to balance the ease of administration with the amount of evidence we have, but I guess it's very exciting that we've got such good preliminary and pivotal evidence for this molecule, infigratinib, so far. But it's a complicated conversation, and one that I probably take sometimes 45 minutes to an hour with families to discuss as part of their routine care. And as you alluded to, quite rightly, it's not a conversation you have and then don't have again, because the landscape is changing rapidly. In almost every 4 months, there's something new coming out.
Dr. Hoover-Fong:
Yep, as the new data come in, we need to explain that to our families.
Dr. Savarirayan:
Yeah, so it's an exciting time for families.
So, again, you've alluded to this, but when families ask, “What can we realistically hope for?” how has that changed, even compared to, say, 12 months ago?
Dr. Hoover-Fong:
That's a good question.
So setting them up for that idea that we're with them for the long haul and that we're going to continue to check in with the safety, with the response, and making sure that we're monitoring for the other potential issues that come along with achondroplasia. This is what's important, and we're committed to it.
Dr. Savarirayan:
Absolutely, and also emphasizing to families, like that you and I do, the treatment doesn't replace all the other care; it doesn't replace the advocacy. Making sure their kindergarten is set up and that people are more tolerant and not using social media inappropriately—doesn't change any of that. It just gives us another option for health.
Dr. Hoover-Fong:
That's super important. Super important. Sleep studies are still needed, good neurologic exams, plotting people on the growth curves to make sure that stays under control.
Dr. Savarirayan:
You still have to come in and see Dr. Ravi and Dr. Julie.
Dr. Hoover-Fong:
Yes, you don't get a free pass.
Dr. Savarirayan:
You don’t get a free pass.
Dr. Hoover-Fong:
This has been great. Before we tie this all up, what's the most important message you think, Ravi, that clinicians should take away from the PROPEL 3 findings and this sort of bigger discussion about growth?
Dr. Savarirayan:
For me, the key takeaway for people watching is that people with achondroplasia have significant medical problems and functional issues, and we now have therapies that might address those and make their lives better. Be aware of them and be aware that one that is emerging is an oral option and that we need to keep finding more about these medications and the balance of their benefits. But it's an exciting time. So please have the conversations with families, because the worst thing would be for a family not to know of these options, and so it'd be great that they're aware and they feel empowered and can at least make an informed decision, even if that decision is no thank you.
Dr. Hoover-Fong:
I agree. I agree. You don't want to be 10 years down the road when the growth plates have closed, there's no chance for any potential benefit, and that's the regret. That's a big regret for us, for the families. So.
Dr. Savarirayan:
Absolutely.
Dr. Hoover-Fong:
Options are there.
Dr. Savarirayan:
Options are there.
Dr. Hoover-Fong:
And that's all the time we have today. I want to thank our audience for joining us, and thank you, Ravi, for having this discussion. It was great to talk with you about this.
Dr. Savarirayan:
Always a pleasure, Julie. Thanks, and goodbye.
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