Children with achondroplasia, the most common form of pediatric dwarfism, have historically had few treatment options.
Some doctors have prescribed growth hormones in hopes of pushing past the average height of around 4 feet 2 inches to 4 feet 4 inches, with little success. Others have attempted to quell the condition’s related health problems — including sleep apnea, spinal curvature, recurrent ear infections and fluid build-up in the skull — through invasive and risky bone lengthening surgeries.
But today, a rising crop of drugs targeting the underlying gene mutation that drives achondroplasia offers a new approach.
BioMarin Pharmaceutical scored the first approval for a cutting-edge achondroplasia treatment Voxzogo in 2021. Children who start taking the drug at 6 months old and stay on it until adulthood could add as much as 10 inches to their projected height, according to the drugmaker’s models. Trial data show that the medication also appears to reduce leg bowing, a common and painful complication seen in children with the condition.
Several other treatments are now also in the works.
The most advanced is TransCon CNP from Ascendis Pharma, which is under priority FDA review with a PDUFA date of Nov. 30. BridgeBio Pharma is in phase 3 with its candidate infigratinib while Tyra Biosciences is developing an oral therapy, dabogratinib, it believes could offer a next-generation approach.
While growth increases are easy to measure, it’s really a surrogate endpoint, said Todd Harris, Tyra’s CEO.
“The broader goal is long-term health outcomes. We have a tagline that we like to use — health beyond height,” he said.
Ultimately, their investigational once-daily pill could achieve both.
A key target
Up-and-coming achondroplasia drugs target the underlying mechanism that drives the condition, a gene mutation affecting fibroblast growth factor receptor 3. This mutation causes the FGFR3 to be overactive, suppressing bone growth, mostly in the upper arms and legs. It also produces characteristic features of the condition, such as a larger-sized head. While the condition can be hereditary, 80% of patients are born to parents without it.
Voxzogo, a biological CNP analog, doesn’t target FGFR3 directly, but acts on a related pathway, while dabogratinib takes aim at FGFR3 head on. It’s a tricky strategy because too much inhibition could spur bone overgrowth or compromise bone strength, raising the risk of fractures, Harris said.
“We want to … turn this gene down, but not off,” he said.
The company’s work on dabogratinib began in a type of bladder cancer that also involves FGFR3, but expanded into achondroplasia once researchers saw enough evidence the drug was safe for children, Harris said. Tyra researchers are now testing a handful of dosages in phase 2, and hope dabogratinib will achieve higher-growth rates than Voxzogo, which doesn’t increase height enough to reach the typical range.
“With direct engagement of … FGFR3, there is the potential to put growth back onto a typical track and lead to better outcomes,” Harris said.
Whether dabogratinib can live up to that promise remains to be seen, but the first batch of data from its phase 2 will likely emerge during the second half of 2026, Harris said.
“We have a unique opportunity with this drug, because unlike gene therapy … we have an opportunity to adjust the signaling pathway on a daily basis, with just a simple pill. So, the hope is that we can bring outcomes, as close to what you'd see in a typical healthy population as we possibly can,” Harris said.
If trial data pans out, they also hope to push treatment to the earliest stages, just weeks after birth, Harris said. For now, the company is focused on earning and keeping the trust of families who are willing to take a chance on this investigational drug.
“We spend a lot of time and energy going to patient group meetings, speaking with advocates who are passionate about this community,” he said. “It's infectious to be part of it.”
