Ascendis Pharma (ASND) Study Update summary

Study design and patient population

• The phase 2 COACH trial enrolled 21 children with achondroplasia aged 2–11 years, including 12 treatment-naive and 9 previously treated with TransCon CNP monotherapy.

• Treatment-naive patients received both TransCon CNP and TransCon Growth Hormone from the outset; experienced patients had growth hormone added to ongoing CNP therapy.

• The primary endpoint was annualized growth velocity at week 52; secondary endpoints included height Z-score, body proportionality, and safety.

• All children completed 52 weeks and continued in the extension trial.

• Baseline demographics were representative of the achondroplasia population, with naive patients being younger on average.

Efficacy and clinical outcomes

• Treatment-naive children achieved an annualized growth velocity of 8.8 cm/year at week 52, a 3.9 cm/year increase from baseline, with a +1.02 SD improvement in height Z-score.

• Previously treated children showed a growth velocity of 8.42 cm/year, a 3.28 cm/year increase, and a height Z-score improvement of +0.86 SD.

• Growth rates exceeded the 97th percentile for average-stature children, representing unprecedented efficacy.

• Durable efficacy was observed, with no waning effect between 26 and 52 weeks and efficacy tripling compared to TransCon CNP monotherapy.

• Improvements in body proportionality and arm span were observed, with arm span surpassing the 84th percentile for achondroplasia.

Safety and tolerability

• The combination of TransCon CNP and Growth Hormone showed an excellent safety profile through week 52, with most adverse events mild or moderate and unrelated to study drugs.

• No symptomatic hypotension, low blood pressure, fractures, or bone-related safety events were observed.

• Injection tolerability was mild and consistent with monotherapies.

• All patients remained on treatment at one year, indicating high tolerability.