European journal of endocrinology · 2026
Navepegritide combined with lonapegsomatropin for the treatment of children with achondroplasia: 52-week results from the phase 2 COACH trial.
СтатьяКлиническое исследование II фазыМногоцентровое исследованиеРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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McDonnell Ciara M, Irving Melita, Nolting Line Aagaard, Abdelrahman Sohair G, Dalby Lene Worsaae, Iklé Jennifer M, Jensen Simon Mejlhede, Komirenko Allison S, Ominsky Michael S, Shu Aimee D, Hove Hanne B
Аннотация
OBJECTIVE: Navepegritide, a prodrug of C-type natriuretic peptide, has demonstrated improved growth and additional benefits, including lower limb alignment, in children with achondroplasia. The well-described mechanism of action of navepegritide in the growth plate is hypothesized to enhance its receptivity to lonapegsomatropin, a prodrug of somatropin, to provide benefits beyond those seen with monotherapies in achondroplasia.
METHODS: In the proof-of-concept phase 2 COACH trial, children with achondroplasia aged 2 to 11 received weekly navepegritide and lonapegsomatropin. The primary efficacy endpoint was annualized growth velocity (AGV) at week 52 vs AGV with navepegritide monotherapy in the ApproaCH trial (NCT05598320).
RESULTS: Twenty-one children were enrolled: 12 received no prior growth-promoting treatment (treatment-naive, TN) and 9 had been receiving navepegritide monotherapy for >1 year (navepegritide-experienced, NE). At week 52, TN children receiving navepegritide and lonapegsomatropin had a least squares mean AGV of 8.69 cm/year versus 5.95 cm/year for matched children who received navepegritide monotherapy, a difference of 2.74 cm/year (P < .0001). Observed mean AGV for TN children was 8.80 cm/year, a +3.89 cm/year increase from baseline (P = .0015). NE children had an observed mean AGV of 8.42 cm/year, a +3.28 cm/year increase from navepegritide-treated baseline (P < .0001). An improvement in body proportionality was observed and arm span increased substantially (+9.4 cm in TN and +7.9 cm in NE children), in line with gains in height. Treatments were well-tolerated with generally mild adverse events and no treatment discontinuations.
CONCLUSIONS: In this prospective trial, the robust growth and anthropometric results suggest that by continuously relieving the pre-hypertrophic block in achondroplasia, navepegritide may make the growth plate more responsive to the strong complementary effect of lonapegsomatropin.
TRIAL REGISTRATION DETAILS: ClinicalTrials.gov NCT06433557.
METHODS: In the proof-of-concept phase 2 COACH trial, children with achondroplasia aged 2 to 11 received weekly navepegritide and lonapegsomatropin. The primary efficacy endpoint was annualized growth velocity (AGV) at week 52 vs AGV with navepegritide monotherapy in the ApproaCH trial (NCT05598320).
RESULTS: Twenty-one children were enrolled: 12 received no prior growth-promoting treatment (treatment-naive, TN) and 9 had been receiving navepegritide monotherapy for >1 year (navepegritide-experienced, NE). At week 52, TN children receiving navepegritide and lonapegsomatropin had a least squares mean AGV of 8.69 cm/year versus 5.95 cm/year for matched children who received navepegritide monotherapy, a difference of 2.74 cm/year (P < .0001). Observed mean AGV for TN children was 8.80 cm/year, a +3.89 cm/year increase from baseline (P = .0015). NE children had an observed mean AGV of 8.42 cm/year, a +3.28 cm/year increase from navepegritide-treated baseline (P < .0001). An improvement in body proportionality was observed and arm span increased substantially (+9.4 cm in TN and +7.9 cm in NE children), in line with gains in height. Treatments were well-tolerated with generally mild adverse events and no treatment discontinuations.
CONCLUSIONS: In this prospective trial, the robust growth and anthropometric results suggest that by continuously relieving the pre-hypertrophic block in achondroplasia, navepegritide may make the growth plate more responsive to the strong complementary effect of lonapegsomatropin.
TRIAL REGISTRATION DETAILS: ClinicalTrials.gov NCT06433557.