navepegritide (TransCon CNP) / Ascendis, Teijin, Specialised Therap - LARVOL DELTA

Ascendis Announces Extension of FDA Review Period for TransCon CNP (navepegritide) for Children with Achondroplasia (GlobeNewswire) - "...In response to the FDA’s ongoing review of the New Drug Application (NDA) for TransCon CNP (navepegritide) for children with achondroplasia,...the FDA has extended the PDUFA target action date by three months to February 28, 2026."

PDUFA • Genetic Disorders

Once-Weekly Navepegritide in Children With Achondroplasia: The APPROACH Randomized Clinical Trial. (PubMed, JAMA Pediatr) - P2/3 | "Moreover, navepegritide demonstrated additional potential health benefits beyond growth. ClinicalTrials.gov Identifier: NCT05598320."

Clinical • Journal • Genetic Disorders • Hypotension • Musculoskeletal Diseases • Obstructive Sleep Apnea • Orthopedics • Respiratory Diseases • Sleep Apnea • Sleep Disorder • FGFR3

Ascendis Pharma A/S…has submitted a Marketing Authorisation Application to the European Medicines Agency for TransCon CNP (navepegritide), a treatment for children with achondroplasia (Investing.com) - "The application is based on data from three randomized, double-blind, placebo-controlled clinical trials and up to three years of open-label extension data, including results from the pivotal ApproaCH Trial....In the United States, TransCon CNP is under priority review by the Food and Drug Administration with a target date of November 30, 2025."

EMA filing • PDUFA • Genetic Disorders

Safety and Tolerability of Navepegritide Treatment in Children With Achondroplasia: 52-Week Results From the Pivotal ApproaCH Trial (ENDO 2025) - "Weekly administration of navepegritide was associated with a low incidence of ISRs and no evidence of treatment-related hypotensive effects. These results suggest that the design of once-weekly navepegritide as a prodrug with a low CNP Cmax contributes to a favorable safety and tolerability profile, and may address limitations of existing ACH therapies and support improved treatment adherence."

Clinical • Genetic Disorders • Hypotension • FGFR3

Improvements in Lower Extremity Alignment are Associated with Physical Functioning in Children With Achondroplasia Treated With Navepegritide: 52-Week Results From the ApproaCH Trial (ASBMR 2025) - No abstract available

Clinical • Genetic Disorders

Once-Weekly Lonapegsomatropin (TransCon hGH) Added to Once-Weekly Navepegritide (TransCon CNP) in Children with Achondroplasia: 26-Week Results from the Phase 2 COACH Trial (ASBMR 2025) - No abstract available

Clinical • Late-breaking abstract • P2 data • Genetic Disorders

FDA Accepts TransCon CNP NDA for Priority Review (GlobeNewswire) - "Ascendis Pharma A/S...announced that the U.S. Food & Drug Administration (FDA) has accepted for priority review its New Drug Application (NDA) for TransCon CNP (navepegritide) for the treatment of children with achondroplasia and has set a Prescription Drug User Fee Act (PDUFA) goal date of November 30, 2025 to complete its review. The FDA also informed Ascendis that they are not currently planning to hold an advisory committee meeting to discuss this application."

FDA filing • PDUFA • Priority review • Genetic Disorders

Effects of Navepegritide on Growth in Children With Achondroplasia: 52-Week Results from the ApproaCH Clinical Trial (ESPE-ESE 2025) - "Statistically significant improvements in ACH-specific height Z-scores in children treated with navepegritide compared with placebo were also observed. These findings suggest that the design of navepegritide – to provide continuous exposure to active CNP – improves growth in children with ACH while maintaining a safety and tolerability profile comparable to placebo."

Clinical • Genetic Disorders • FGFR3

Effects of Navepegritide on Bone Morphometry in Children With Achondroplasia: 52-Week Results from the ApproaCH Clinical Trial (ESPE-ESE 2025) - "Conclusion In the ApproaCH trial, weekly administration of navepegritide demonstrated superiority over placebo in AGV and improved aspects of bone morphometry in children with ACH. These findings highlight that the design of navepegritide, which provides continuous exposure to active CNP, may deliver benefits that go beyond promoting linear growth – actively targeting and addressing critical aspects of skeletal dysplasia in ACH, which are key contributors to health-related complications."

Clinical • Genetic Disorders • Orthopedics • Pain • FGFR3

teACH: A Clinical Trial to Evaluate Efficacy and Safety of Navepegritide in Adolescents (12 - 18 Years of Age) With Achondroplasia. (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Ascendis Pharma A/S

New P2 trial • Genetic Disorders

COACH: A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With Lonapegsomatropin in Children With Achondroplasia (clinicaltrials.gov) - P2 | N=22 | Active, not recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Genetic Disorders

A Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of TransCon CNP Administered Once Weekly in Prepubertal Children With Achondroplasia (clinicaltrials.gov) - P2 | N=57 | Completed | Sponsor: Ascendis Pharma A/S | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders

Progress in managing children with achondroplasia. (PubMed, Expert Rev Endocrinol Metab) - "This review discusses key advances in the therapeutic management of children with achondroplasia, including vosoritide, the first approved drug, and other emerging precision therapies. These include navepegritide, a long-acting form of C-type natriuretic peptide, and infigratinib, a tyrosine kinase receptor inhibitor, summarizing trial outcomes to date...These new treatment options highlight the importance of prompt prenatal identification and subsequent testing of a suspected fetus with achondroplasia and counseling of families. It is hoped that, in the near future, families will have the option to consider a range of effective targeted therapies that best suit their child with achondroplasia, starting from birth should they choose."

Journal • Review • Genetic Disorders

COACH: A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With Lonapegsomatropin in Children With Achondroplasia (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Genetic Disorders

COACH: A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With Lonapegsomatropin in Children With Achondroplasia (clinicaltrials.gov) - P2 | N=18 | Not yet recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S

Combination therapy • New P2 trial • Genetic Disorders

A Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of TransCon CNP Administered Once Weekly in Prepubertal Children With Achondroplasia (clinicaltrials.gov) - P2 | N=57 | Active, not recruiting | Sponsor: Ascendis Pharma A/S

Trial completion date • Genetic Disorders

A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Infants (0 to <2 Years of Age) With Achondroplasia (clinicaltrials.gov) - P2 | N=72 | Recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders

ApproaCH: A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Children With Achondroplasia (clinicaltrials.gov) - P2/3 | N=84 | Active, not recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S | Phase classification: P2b ➔ P2/3

Phase classification • Genetic Disorders

Once-Weekly TransCon CNP Achieved Primary Efficacy Objective in ACcomplisH China Phase 2 Trial (PRNewswire) - P2 | N=57 | ACcomplisH (NCT04085523) | Sponsor: Ascendis Pharma A/S | "VISEN Pharmaceuticals...is pleased to announce the topline results from the ACcomplisH China Phase 2 Trial in children with achondroplasia (ACH) aged 2 to 10 years. In the trial, patients dosed with TransCon CNP at the 100 μg CNP/kg/week showed significantly higher annualized growth velocity (AGV) than placebo (1.180 cm/year, P=0.018) at Week 52...The ACcomplisH China Phase 2 Trial was a randomized, double-blind, placebo-controlled clinical trial conducted across 6 investigational sites in China. The study aimed to evaluate the safety and efficacy of once-weekly TransCon CNP compared to placebo in children with ACH aged 2 to 10 years old.

P2 data • Genetic Disorders