For years, no medication was available to help children with hypochondroplasia grow meaningfully taller. Human growth hormone could speed up how quickly they grew during the first year of use, but in general, it didn't seem to increase adult heights.
Today, newer medicines show promise for adding inches to stature, including for children with hypochondroplasia. Still, as with many new medications, there is some risk. The research is new and ongoing, and doctors aren't yet sure of all the long-term effects of these medicines. Consult your doctor to help you weigh the pros, cons, and unknowns of using these medications.
Ahead, skeletal dysplasia experts explain how these medications work, what the possible benefits and risks are, and what key questions and challenges parents should consider.
Height-Boosting Injections
Among newer growth drugs, the one that's been studied the most so far is Voxzogo (vosoritide). It's a daily injection available to children with hypochondroplasia through clinical trials. It's already earned FDA approval for use in children with achondroplasia, a related condition that leads to more-severe symptoms. (Both conditions usually are caused by a change, or mutation, in the FGFR3 gene.)
Voxzogo is a type of drug called a CNP analog. It helps push on the gas pedal for growth, says Ricki S. Carroll, MD, a complex care doctor on the skeletal dysplasia team at Nemours Children's Hospital in Delaware. Voxzogo aims to counter the growth-slowing effects of hypochondroplasia, in which children's bones grow at a slower rate than that of their peers.
Voxzogo is a daily shot because it stays in your body for a short time. "It basically revs the engine or pushes on the gas pedal for 20 to 30 minutes, and then it's broken down and excreted," Carroll says. The goal over time is to boost the yearly growth rate and lead to a higher adult height, she says. A child can stay on Voxzogo until their growth plates — areas of new bone growth in children and teens — close in their teens.
In one clinical trial of children ages 3 to 17 with hypochondroplasia, those who took Voxzogo for a year grew an average of almost an inch (2.33 centimeters) taller than those who took a placebo.
A newer CNP analog drug called Yuviwel (navepegritide) works similarly to Voxzogo. It stays in the body longer, so it's given as a weekly shot instead of a daily one. Yuviwel hasn't yet been tested in clinical trials for children with hypochondroplasia, but the FDA has approved it for those with achondroplasia. In one clinical trial of children ages 2 to 11 with achondroplasia, those who took Yuviwel for a year grew an average of just over half an inch (1.5 centimeters) taller compared with those who received a placebo.
Height-Boosting Oral Drugs
Skeletal dysplasia experts have their eyes on two drugs taken by mouth: infigratinib and dabogratinib. A phase 2 trial of infigratinib for kids with hypochondroplasia is slated to start soon. Trials of dabogratinib for hypochondroplasia should start relatively soon as well.
Both drugs are known as FGFR inhibitors. They tame the activity of the mutated FGFR3 gene that's often the cause of hypochondroplasia and achondroplasia. FGFR inhibitors are "essentially trying to take the foot off the brake pedal [for growth], as opposed to pushing on the gas pedal" the way height-boosting shots do, Carroll says.
The fact that a child could take a daily pill in "a scoop of yogurt or applesauce" rather than getting a shot "is a huge deal," Carroll says. "I think that's very appealing to a lot of families."
For now, clinical trials of infigratinib are further along in children with achondroplasia. The trials "have been safe and [have] shown an increase in linear growth as compared to untreated children," says Julie E. Hoover-Fong, MD, PhD, director of the Greenberg Center for Skeletal Dysplasia at Johns Hopkins in Baltimore.
Hoover-Fong was the co-lead researcher on a phase 3 trial in which children with achondroplasia who took infigratinib daily grew an average of almost three-quarters of an inch (1.74 centimeters) taller than those who got a placebo pill over the course of a year. The drug also improved the proportions of their bodies.
The children enrolled in these trials continue to be followed to find out if the increased linear growth continues year-after-year, Hoover-Fong says.
Side Effects and Possible Risks of Height-Boosting Drugs
While the short-term side effects of injectable and oral medications are becoming clearer, the long-term risks will take researchers much more time to figure out.
Some common side effects of shots, like Voxzogo and Yuviwel, are redness or swelling where the shot was given, and vomiting. It's possible to have a drop in blood pressure after taking a dose, too, which could make a child lightheaded or dizzy.
Some possible concerns include unscientific reports of an increase in scoliosis (abnormal spine curvature) or femur fractures in children who took Voxzogo, Carroll says. Also, in studies of Voxzogo use for other growth conditions (not including hypochondroplasia or achondroplasia), there have been lots of reports of a hip condition called slipped capital femoral epiphysis (SCFE), she says. Researchers are looking into whether these effects could be caused by the medication.
The possible side effects of oral meds in children with hypochondroplasia and achondroplasia are still emerging. So far, clinical trials of children taking infigratinib have spotted side effects like fatigue, joint pain, constipation, and less appetite. Researchers also have noted isolated incidents of fluid buildup in the brain (hydrocephalus), enlarged adenoids, enlarged tonsils, sleep apnea, a growth in the middle ear (cholesteatoma), and a bacterial infection.
The known side effects of the oral drug dabogratinib mainly come from studies of other health conditions. For instance, a trial of the drug for people with urothelial carcinoma noted diarrhea, and a lab finding indicating elevated liver enzymes in the blood.
As with the height-boosting shots, researchers will need much more time to learn about the possible long-term risks of taking oral medications for hypochondroplasia. Researchers of both the shots and the pills also hope to find out if these drugs have long-term benefits, such as lessening hypochondroplasia complications.
If you're thinking about enrolling your child with hypochondroplasia in a clinical trial for a drug that aims to boost height, ask the doctor to explain all the possible pros and cons, and what a realistic outcome of treatment might be, given your child's age and health.
Other Challenges and Questions to Consider
Injections and oral medicines that aim to boost height are relatively new drugs, so they'll need to go through more clinical trials before the FDA decides whether or not to approve them for more general use in children with hypochondroplasia.
When it comes to enrolling a child in a clinical trial, "there are certainly some families that say, 'I just can't see doing it without more data. Maybe my child will want to use it for their own children.' And that's fine," Hoover-Fong says. "It's encouraging when a medication has gone through the rigorous FDA process, so you can feel that it's as safe as possible."
We simply don't yet know all the potential risks and benefits of new treatments, especially something still in a clinical trial, says Mahim Jain, MD, orthogenetics director at Nemours Children's Hospital.
"There's a lot of unknowns entering it. We do the best we can ahead of time to really understand the potential medicine and what it's targeting to anticipate what potential side effects or risks there could be. But part of being in a trial is going to be trying to make sure that the medicine is safe," he says.
He likes to make clear that being in a clinical trial is a commitment for families: "Often, as we're running a trial, we have very narrow windows of time when we have to have certain visits done. It often will involve families having to travel."
Carroll also talks with families about the mental health aspect of giving children with short stature height-boosting medication. "We want to instill confidence and help children feel pride in who they are, and then we're also injecting them with a drug to make them grow more," Carroll says.
"What does that mean for them? And how do we continue to support them while also giving them a medication to change them?"
Another question for parents to mull: How important is it to change your child's height? "There are many people in the short stature community that don't feel that short stature is something that needs to be changed. It's part of that person's identity," Hoover-Fong says. More important to the well-being of a child with hypochondroplasia, she says, is routine visits with a multidisciplinary health care team (to nip any complications in the bud) and, if needed, social support from other people of short stature.