Ascendis Pharma A/S (NASDAQ:ASND) executives highlighted topline Week 52 results from the company’s Phase 2 COACH trial, which is evaluating a once-weekly combination regimen of TransCon CNP and TransCon Growth Hormone (TransCon hGH) in children with achondroplasia. Management said the one-year data support the company’s view that adding TransCon hGH to TransCon CNP can “boost” outcomes beyond TransCon CNP monotherapy, while maintaining a safety and tolerability profile consistent with each agent individually.
COACH trial design and patient population
Chief Medical Officer Aimee Shu said COACH enrolled 21 children with achondroplasia. The study included two cohorts:
- TransCon CNP treatment-naïve cohort (n=12): received TransCon CNP plus TransCon Growth Hormone from the outset.
- TransCon CNP treatment-experienced cohort (n=9): previously received TransCon CNP monotherapy in another Ascendis trial, and had TransCon Growth Hormone added on top.
Week 52 efficacy: growth velocity and height Z-scores
President and CEO Jan Møller Mikkelsen and Shu both emphasized that AGV levels observed at one year were higher than what they described as historical benchmarks in achondroplasia.
In the treatment-naïve cohort, Shu reported AGV of 8.8 cm/year at Week 52, an increase of 3.9 cm/year from baseline, which she said was statistically significant. Achondroplasia-specific height Z-score increased from 0.46 to 1.47 (a +1.02 change), which Shu compared to a roughly 0.3 standard deviation change observed with vosoritide monotherapy in Ascendis’ Phase 3 trial.
In the TransCon CNP-experienced cohort, Shu said AGV at Week 52 was 8.42 cm/year, an increase of 3.28 cm/year versus baseline, also statistically significant. Height Z-score reached 2.15 at Week 52, representing a +0.86 change from the TransCon CNP-treated baseline (Shu also described this change as statistically significant).
Management also discussed the shape of the response over time, stating the growth effect did not “wind off” between Week 26 and Week 52. Mikkelsen said the trial achieved 100% patient retention through the first year, which he characterized as unusual for a one-year study and supportive of tolerability.
Benefits beyond linear growth: proportionality and arm span
Ascendis framed the trial as aiming to address comorbidities beyond height. Shu said upper-to-lower body segment ratio improved in both cohorts over 52 weeks, with reductions greater than those seen with TransCon CNP monotherapy, which she described as a marker of improved body proportionality (lengthening of the lower body segment relative to the torso).
Shu also highlighted arm span data, describing a “statistically significant increase” in arm span and showing children “cutting across” natural history isopleths and “approaching the 84th percentile” for arm span compared to natural history in achondroplasia. She added that arm span is of interest to both regulators and patients, offering examples such as improved reach for cooking or driving without vehicle modification.
Safety and tolerability at one year
Shu said the combination used TransCon CNP at 100 mcg/kg/week and a starting dose of TransCon Growth Hormone at 0.30 mg/kg/week. Through Week 52, she described the safety profile as “excellent” and similar to each agent alone, with adverse events generally mild and unrelated; she said 85% of adverse events were Grade 1. She reported no symptomatic hypotension, no fractures, and one participant with two serious adverse events that were determined not to be related to study drugs.
Shu also stated that bone age remained consistent with chronological age at Week 52, and injection tolerability was consistent with TransCon CNP alone and TransCon Growth Hormone alone, with all injection tolerability events adjudicated as mild.
Development plans: Phase 3 preparation, dosing approach, and regulatory context
Management said Ascendis began preparing in Q4 for a Phase 3 trial in achondroplasia, describing a “simple” design with two arms: TransCon CNP monotherapy versus combination therapy. Mikkelsen said the primary endpoint would remain linear growth, noting it is established by the FDA, and said the company intends to emphasize additional measures such as body proportionality, leg bowing, arm span, and quality of life.
On how the regimen might be used long term, Mikkelsen described TransCon CNP as a background therapy with TransCon Growth Hormone used as an intermittent “boost,” potentially over two-year periods with breaks, depending on physician, patient, and caregiver decisions. In response to questions on administration, Mikkelsen said patients currently receive two injections weekly in the trial and that the company’s life-cycle management vision is to integrate into a single injection over time, though he said that will take time.
Regarding TransCon CNP’s regulatory status, Mikkelsen said the company is waiting for U.S. approval and is “confident that it’s happening in the near future.” Later, he said the company had answered FDA questions before the year started and had not received additional requests, and was “just sitting and waiting” for a decision. He also said the labeling for TransCon CNP had “more or less” been finalized and that the combination program would build into the TransCon CNP filing, noting the company is continuing under the TransCon CNP IND rather than filing a new IND.
Management also touched on payer considerations and pricing. Mikkelsen said views will differ by country, and argued that adding Skytrofa (Ascendis’ TransCon Growth Hormone) would not be “highly impactful” to the cost structure relative to the benefit. On U.S. pricing mechanics, he said that, until a single-injection presentation is developed, the combination would likely be a TransCon CNP presentation plus a Skytrofa presentation, and that “typically” pricing would be driven by the sum of the two.
About Ascendis Pharma A/S (NASDAQ:ASND)
Ascendis Pharma A/S is a Denmark‐based biopharmaceutical company focused on developing innovative therapies for rare endocrine diseases. Founded in 2015 and headquartered in Hellerup, the company leverages its proprietary TransCon drug delivery platform to create long‐acting prodrugs designed to improve safety, efficacy and patient convenience. Ascendis Pharma maintains research and development operations in Europe and the United States, with clinical studies spanning North America, Europe and Asia.
The company’s lead product, lonapegsomatropin (Skytrofa®), is a once‐weekly growth hormone therapy approved by the U.S.
