An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
From Ascendis: COACH Week 78 Results and Provides Update on Achondroplasia Programs and YUVIWEL® Uptake in the U.S.
On August 6, 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% 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.”
Monotherapy Update
(TransCon CNP; navepegritide)
In completed and ongoing clinical trials of children with achondroplasia, treatment with once-weekly TransCon CNP monotherapy demonstrated durable improvements in height, as well as benefits beyond height, and a safety and tolerability profile similar to placebo, including a low rate of injection site reactions, consistent with the incidence rate reported in the FDA label.
- Week 104 data from the pivotal ApproaCH Trial of TransCon CNP at 100 µg/kg once-weekly in children with achondroplasia aged 2 to 11 years demonstrated:
- Durable improvements in height as measured by AGV and height Z-scores over 104 weeks for those randomized to TransCon CNP, and significant improvement for those switching from placebo to TransCon CNP at Week 52.
- Benefits beyond height with TransCon CNP monotherapy, including improvements in lower limb alignment and body proportionality, as demonstrated by improved tibial-femoral angle and upper-to-lower body segment ratio, respectively, with durable treatment effect over 104 weeks for those randomized to TransCon CNP, and substantial improvement at Week 104 for those switching from placebo to TransCon CNP at Week 52.
- Through two years of treatment, TransCon CNP was generally well-tolerated. Most adverse events in TransCon CNP-treated children were mild or moderate, with none leading to treatment discontinuation or withdrawal from the trial. There were no occurrences of symptomatic hypotension, and the overall rate of injection-site reactions, all of which were mild, was 0.35 per person-year of exposure.
- Completed target enrollment for pivotal reACHin Trial, supporting planned regulatory filings for infants 0 to <2 years of age with achondroplasia.
- To date, 96% of the 140 children enrolled in the AttaCH long-term open-label extension trial remain on TransCon CNP monotherapy, with up to nearly 6 years of treatment, or are in the ongoing COACH combination therapy trial.
- The AttaCH Trial, following children to near-final adult height, continues to enroll children who complete TransCon CNP monotherapy trials (ACcomplisH, ApproaCH, teACH, and reACHin).
- The ongoing pivotal reACHin Trial is evaluating the safety, tolerability, and efficacy of TransCon CNP in infants with achondroplasia (aged 0 to <2 years).
- The ongoing pivotal teACH Trial is evaluating the safety, tolerability, and efficacy of TransCon CNP in adolescents with achondroplasia (aged 12 to <18 years).
- In the European Union, a decision is anticipated in the fourth quarter of 2026 for the Marketing Authorisation Application for TransCon CNP as a monotherapy for children with achondroplasia.
“I am excited to see compelling long-term efficacy, safety, and tolerability data for TransCon CNP monotherapy,” said Carlos Bacino, MD, FACMG, Professor of Molecular and Human Genetics, Baylor College of Medicine and Texas Children’s Hospital. “TransCon CNP has demonstrated positive effects compared to placebo on multiple aspects of skeletal growth, including statistically significant improvements in height and lower-limb alignment, with growing long-term data highlighting its unprecedented efficacy when used in combination with TransCon hGH. That and its once-weekly administration and low rate of injection site reactions mark it as an important potential new treatment option for children with achondroplasia.”
“We are encouraged to see research on navepegritide continue to examine areas the achondroplasia community has identified as important, including outcomes beyond linear growth,” said Mike Hughes, Chair, Biotech Industry Liaison Committee, Little People of America. “The ApproaCH findings add to our understanding of body proportionality and lower-limb alignment, while continued study will be important to determine whether these anatomical changes translate into meaningful differences in function, mobility, or the future need for surgical intervention. Clear, balanced evidence can help individuals and families make informed decisions aligned with their own goals and values, including whether treatment is right for them.”
