Evaluating Long-Acting CNP Therapy in Achondroplasia

This episode, titled “Evaluating Long-Acting CNP Therapy in Achondroplasia,” features panelists examining the mechanism and clinical evidence supporting once-weekly CNP prodrug therapy. The panel first discusses how the TransCon platform extends exposure to active CNP. Following subcutaneous administration, active CNP is gradually released from the prodrug, allowing a much longer effective half-life than native circulating CNP and supporting once-weekly administration. Once released, the peptide can bind its receptor and counteract the excessive FGFR3 signaling that impairs normal chondrocyte proliferation.

The discussion then turns to the pivotal phase 3 ApproaCH trial, which enrolled children with achondroplasia and evaluated efficacy and safety. The panel reviews the improvement in annualized growth velocity compared with placebo and highlights additional outcomes related to skeletal structure and physical function. These include tibial-femoral angle, mechanical axis deviation, lower-extremity proportionality, and parent-reported measures of physical function. Safety findings are also reviewed, including low rates of injection-site reactions and the absence of clinically significant hypotension or treatment-related discontinuations. The panel discusses the presence of antibodies in some participants but notes that they did not appear to affect clinical outcomes.

Two-year follow-up data add evidence of sustained growth benefit and continued improvement in lower-extremity alignment, raising questions about whether these changes may ultimately influence gait or future orthopedic needs.

In the next episode, “Exploring Combination Therapy in Achondroplasia,” panelists will examine a strategy combining navepegritide with long-acting growth hormone. They will discuss early growth findings as well as questions about bone age, durability, and long-term safety.