Ascendis Pharma A/S provided updates across its achondroplasia programs.
“The rapid uptake of YUVIWEL in the United States underscores its highly differentiated profile and reflects our core values and our patient-centered development of therapies,” said Jan Mikkelsen, President and Chief Executive Officer of Ascendis Pharma. “We are very pleased to see continued unprecedented results from our combination therapy trial, which further reinforce our commitment to ensure that as many children as possible can access YUVIWEL.”
Combination Therapy Update
(TransCon CNP + TransCon hGH; navepegritide + lonapegsomatropin)
Treatment with the combination of once-weekly TransCon CNP and once-weekly TransCon hGH continued to demonstrate durable growth in children with achondroplasia, with a mean annualized growth velocity (AGV) meeting or exceeding the 97th percentile of children of average stature, without compromising safety or tolerability at Week 78.
Highlights of the Topline Week 78 COACH Trial Results
Consistent with Week 26 and Week 52 results, mean AGV for children treated with combination therapy through Week 78 remained at or above the 97th percentile AGV of children of average stature, with changes over time following age-related growth patterns, and sustained increases in ACH height Z-score, indicating a tripling of efficacy compared to TransCon CNP monotherapy.
For the TransCon CNP treatment-naïve cohort, mean AGV at Week 78 was 7.73 cm/year, with an increase in mean ACH height Z-score of +1.29, increasing from 0.46 to 1.75 over 78 weeks.
For the TransCon CNP-experienced cohort (mean treatment duration with TransCon CNP of 2.56 years), mean AGV at Week 78 was 7.67 cm/year, with an improvement in mean ACH height Z-score of +1.10, increasing from 1.28 to 2.38 over 78 weeks.
Children treated with combination therapy demonstrated continued improvements in body proportionality through Week 78, aligning with the increase in linear growth.
Safety and tolerability were consistent with those observed for TransCon CNP and TransCon hGH monotherapies. Combination therapy was generally well-tolerated, with a low incidence of injection site reactions and generally mild treatment-emergent adverse events (TEAEs).
To date, 100 per cent of the 21 enrolled children completed 78 weeks of treatment and remain on therapy in the COACH Trial.
Additional data from Week 78 of COACH to be presented at an upcoming medical meeting.
COACH Trial Design
COACH is an ongoing prospective Phase 2 open-label trial to investigate the efficacy, safety, and tolerability of combined treatment with once-weekly TransCon CNP at 100 µg/kg/week and once-weekly TransCon hGH at a starting dose of 0.30 mg/kg/week (“combination therapy”) in children with achondroplasia aged 2 to 11 years. The trial included a cohort of TransCon CNP treatment-naïve children (N=12, mean age 5.26 years) and a cohort of previously TransCon CNP-treated children (N=9, mean age 8.32 years), who had received TransCon CNP (100 µg/kg/week) for a mean of 2.56 years in clinical trials. The trial population is representative of children with achondroplasia and the prior treatment benefits of TransCon CNP monotherapy.
“I became involved in advocacy in part because parents were increasingly eager to learn more about emerging drug development programs,” said Chandler Crews, Founder of The Chandler Project. “YUVIWEL is a new treatment option that has brought hope to many in our community seeking to prevent complications of achondroplasia that may, without effective pharmacologic treatment, lead to chronic pain, mobility issues, surgeries, and impact on quality of life.”
