ESPE Abstracts

Introduction: Achondroplasia is caused by a pathogenic mutation in the FGFR3 gene, leading to impaired endochondral bone growth and multiple medical complications. Vosoritide, a modified recombinant human C-type natriuretic peptide (rhCNP), was approved by the European Medicines Agency (EMA) in August 2021 for treating genetically confirmed achondroplasia in patients aged ≥2 years until closure of epiphyses. Acorn is the first treatment-based registry for achondroplasia, created to monitor long-term safety of vosoritide treatment in real world use.

Methods: Acorn is a multicenter, non-interventional post-authorisation safety study (PASS) requested by the EMA as part of the risk management plan (Category 3 per Risk Management Plan). The study aims to recruit approximately 330 patients into 2 cohorts: (1) incident users aged ≥ 2 to ≤ 8 years old, defined as those who either recently started, or plan to start treatment with vosoritide, and (2) prevalent users aged ≥ 2 years old who initiated treatment as part of the French expanded access program or vosoritide open-label clinical trial. The primary objective is to evaluate the long-term impact of treatment on adverse bone-related safety events, such as fractures and slipped capital femoral epiphyses. Secondary objectives include evaluating the long-term impact of treatment on safety and disease-related outcomes, including achondroplasia-related complications/surgeries and changes in height and weight. The study period is 10 years from the date of first patient enrolled. In addition, patients who complete (reach final adult height) or discontinue treatment during the study, will be followed up 2 years later. Almost all vosoritide treated patients aged ≥ 2 years old to ≤ 8 years will be eligible for the study, leading to a more representative population of achondroplasia patients than in clinical trials. As an observational study, data collected will reflect standard clinical practice and real-life management and treatment use.

Results: The protocol was approved by the EMA in July 2023 and is registered on the EU post authorization study (PAS) register (EUPAS47514). In total, 8-10 countries and ~30 sites are involved; ethics submissions are ongoing. The first patient was enrolled in April 2023 and further data will be shared on the number, location and demographics of patients enrolled.

Conclusion: Vosoritide is the first approved medicinal treatment for children with achondroplasia. Acorn will collect important long-term, real-world data from patients across Europe, and will provide important insights into the impact of long-term treatment on safety, effectiveness and the use of vosoritide in context of other interventions.