Voxzogo (vosoritide) / BioMarin - LARVOL DELTA

Early Neonatal Administration of Vosoritide in Achondroplasia: A Report of Two Cases. (PubMed, Am J Med Genet A) - "These observations are descriptive and hypothesis-generating only and do not support changes in current clinical practice. Further data are required to clarify the potential benefits and limitations of initiating vosoritide therapy during the neonatal period."

Journal • Genetic Disorders • FGFR3

Safety and Efficacy of Voxzogo for Growth Deficits in MPS IVA and VI (clinicaltrials.gov) - P1/2 | N=6 | Active, not recruiting | Sponsor: University of California, San Francisco | Trial completion date: Dec 2026 ➔ Dec 2029 | Trial primary completion date: Dec 2025 ➔ Dec 2028

Trial completion date • Trial primary completion date

852370: When the Trial Ends Early: Perspectives on Premature Clinical Trial Closures in Rare Disease Therapeutics (ACMG 2026) - "Medical genetics has entered a new therapeutic era, with increasing FDA approvals for rare disease treatments such as pegvaliase, vosoritide, and Skysona. Dr. Melinda Peters will offer a regulatory view on the complex aftermath of abruptly halted trials.Together, these perspectives highlight the need for sustainable, ethical frameworks to advance therapeutics in rare disease care.Learning Objectives:• Describe the evolution of therapeutic development in medical genetics and its impact on rare disease management.• Identify the regulatory, ethical, and practical challenges posed by premature clinical trial terminations.• Discuss the psychological and clinical consequences of early trial closure on affected patients and families.• Evaluate potential strategies for maintaining patient care continuity when investigational therapies are halted."

Clinical • Cognitive Disorders • Rare Diseases

ASPEN: A Phase 2/3 Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia (clinicaltrials.gov) - P2/3 | N=160 | Not yet recruiting | Sponsor: BioMarin Pharmaceutical

New P2/3 trial • Genetic Disorders

Development of Muscle Function in Children with Achondroplasia Under Vosoritide Treatment: A Retrospective Single-Centre Observational Study. (PubMed, J Musculoskelet Neuronal Interact) - "While vosoritide produced significant height gains, no significant changes in muscle function z-scores were observed in this cohort. These findings are exploratory and suggest that muscle function may develop in parallel with that of unaffected children."

Journal • Observational data • Retrospective data • Genetic Disorders • FGFR3

Effect of vosoritide on spine morphology in children with achondroplasia: 1-year results from a randomized phase 2 study. (PubMed, J Endocr Soc) - P2 | "These preliminary results suggest that early vosoritide treatment may improve spinal morphology and reduce the risk of spinal stenosis in children with achondroplasia. Clinical Trial Information: NCT03583697."

Clinical • Journal • P2 data • Genetic Disorders • Musculoskeletal Diseases • Orthopedics

Effect of vosoritide on genu varum in children with achondroplasia after 1 year in randomized placebo-controlled trials. (PubMed, J Endocr Soc) - P2, P3 | "Children aged ≥5 years improved in ankle joint to distal fibula physis distance (difference in LSM change from baseline, -0.07, P = .010) and fibula/tibia ratio (-0.025, P < .0001), and children aged 2-5 years had improved fibula/tibia ratio (-0.033, P = .0032). Preliminary results suggest vosoritide may improve or limit genu varum in children with achondroplasia."

Clinical • Journal • Genetic Disorders • Orthopedics • Pain

111-212: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Vosoritide in Infants and Young Children with Hypochondroplasia, Aged 0 to < 36 Months (clinicaltrialsregister.eu) - P1/2 | N=30 | Recruiting | Sponsor: Biomarin Pharmaceutical Inc.

New P1/2 trial

111-308: Long-Term Extension Study of Vosoritide to Treat Children with Hypochondroplasia (clinicaltrialsregister.eu) - P2/3 | N=44 | Recruiting | Sponsor: Biomarin Pharmaceutical Inc.

New P2/3 trial

An Extension Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia (clinicaltrials.gov) - P3 | N=119 | Active, not recruiting | Sponsor: BioMarin Pharmaceutical | Trial completion date: Dec 2024 ➔ Jun 2031 | Trial primary completion date: Oct 2024 ➔ Jun 2031

Trial completion date • Trial primary completion date • Genetic Disorders

An Extension Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia (clinicaltrials.gov) - P3 | N=119 | Active, not recruiting | Sponsor: BioMarin Pharmaceutical | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Genetic Disorders

A Study to Evaluate Long-Term Safety, Tolerability, & Efficacy of BMN 111 in Children With Achondroplasia (ACH) (clinicaltrials.gov) - P2 | N=46 | Enrolling by invitation | Sponsor: BioMarin Pharmaceutical

New P2 trial • Genetic Disorders

A Study to Evaluate Long-Term Safety, Tolerability, & Efficacy of BMN 111 in Children With Achondroplasia (ACH) (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: BioMarin Pharmaceutical | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Genetic Disorders

A Study to Evaluate Long-Term Safety, Tolerability, & Efficacy of BMN 111 in Children With Achondroplasia (ACH) (clinicaltrials.gov) - P2 | N=30 | Enrolling by invitation | Sponsor: BioMarin Pharmaceutical | N=46 ➔ 30

Enrollment change • Genetic Disorders

A Study to Evaluate Long-Term Safety, Tolerability, & Efficacy of BMN 111 in Children With Achondroplasia (ACH) (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: BioMarin Pharmaceutical | Trial completion date: Oct 2022 ➔ Feb 2028 | Trial primary completion date: Oct 2022 ➔ Dec 2027

Trial completion date • Trial primary completion date • Genetic Disorders

Maternal decision-making through temporal uncertainties: The anticipatory biopolitics of Vosoritide in dwarfism communities. (PubMed, Soc Sci Med) - "Vosoritide emerges not only as a site of biomedical possibility, but also as a biopolitical discourse, shaping how mothers of children with dwarfism (re)imagine and manage their child's body, future, and identity. In doing so, this research advances sociological scholarship by exposing the temporal and anticipatory 'logics' through which biopower operates in the governance of dwarfism."

Journal • Endocrine Disorders • Genetic Disorders

FGFR antagonists avoid pseudarthrosis in a mouse model of osteochondrodysplasia. (HMGC 2026) - "Lastly, we found that treatment with a tyrosine kinase inhibitor (BGJ398, infigratinib) or a C-type natriuretic peptide (BMN111, vosoritide) fully rescued the defective endochondral bone repair observed in Hch mice. Taken as a whole, our findings show that FGFR3 is a critical orchestrator of bone repair and provide a rationale for the development of potential treatments for patients with FGFR3-osteochondrodysplasia."

Preclinical • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • BIRC2 • DUSP9 • FGFR • FGFR2 • FGFR3 • SOCS3

Vosoritide Therapy in a Patient with Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans (ACMG 2026) - "Conclusion Our case demonstrates that vosoritide use in SADDAN leads to improved growth and lung function. Studies are needed to confirm the beneficial effects and further evaluate the long-term outcomes of vosoritide use in SADDAN."

Clinical • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Orthopedics • Pulmonary Disease • Respiratory Diseases • FGFR3

From Early Access to Routine Care: Prospective Real-World Follow-Up of Vosoritide in Achondroplasia in France (ACMG 2026) - "Vosoritide demonstrated sustained growth benefits over 36 months in children with achondroplasia. No tachyphylaxis, treatment interruption, or new safety signals were observed in routine care. This real-world experience aligns with published data and supports early and long-term use of vosoritide in children with achondroplasia to optimize patient outcomes."

Clinical • Real-world • Real-world evidence • Genetic Disorders • Mood Disorders • Orthopedics • FGFR3

Effectiveness of Vosoritide in Children with Achondroplasia Starting Treatment Aged <2 Years: Interim Results from a Japanese Real-World Study (ACMG 2026) - "Children with achondroplasia aged <2 years had good adherence to early vosoritide initiation, with no consecutive missed doses of clinical significance, treatment interruptions, or discontinuations for any reason. Interim results from the first year of the study show robust growth benefit with vosoritide, comparable to that reported in clinical trials in this population. Data from this study will enable assessment of the impact of early vosoritide initiation on brain morphology, surgical burden, and common complications associated with achondroplasia."

Clinical • Real-world • Real-world evidence • Genetic Disorders • Orthopedics • FGFR3

Early Start, Maximum Impact: Long-term Trial Data Supporting Cumulative Clinical Benefit in Children Who Initiated Vosoritide <2 Years Old (ACMG 2026) - P2, P3 | "Vosoritide continues to be well tolerated with high adherence. Durable improvements in height while maintaining stable arm-to-height ratios suggests arm span improvements beyond untreated comparators. Body proportionality and BMI trajectories also improved in children with achondroplasia who initiated treatment aged <2 years vs untreated comparators, supporting guidelines recommending early treatment initiation to maximize clinical benefit."

Clinical • Genetic Disorders • Orthopedics

Interim Real-World Results from the Acorn Study: Long-Term Safety and Growth Outcomes of Vosoritide in Children with Achondroplasia (ACMG 2026) - "The safety of vosoritide was consistent with clinical trials, and no new safety signals occurred. Interim results also suggest a trend toward clinical benefits and sustained growth across ages with vosoritide in a real-world setting for up to 3 years, with good adherence and very few treatment discontinuations. The available results highlight the potential for starting vosoritide treatment early to maximize clinical benefits, such as fewer surgeries, while also maintaining a manageable and predictable safety profile."

Clinical • Real-world • Real-world evidence • Genetic Disorders • Musculoskeletal Diseases • Orthopedics • Rheumatology • FGFR3

Long-Term Vosoritide Improves Bone Mineral Density and Bone Content in Children with Achondroplasia: Results from Quantitative Computed Tomography Analyses (ACMG 2026) - P2 | "Long-term vosoritide over 9 years of treatment was associated with improvement in bone growth parameters in this single-arm analysis, as measured by the QCT analyses. These data complement the previously reported annual height increases in children receiving vosoritide. Overall, long-term vosoritide treatment may potentially improve bone strength over time in children with ACH."

Clinical • Genetic Disorders

BODY COMPOSITION CHANGES DURING 12-MONTH VOSORITIDE TREATMENT IN CHILDREN WITH HYPOCHONDROPLASIA: A DXA-BASED PROSPECTIVE STUDY (ACMG 2026) - P2 | "In this prospective 12-month study, vosoritide treatment in children with HCH led to a significant increase in lean mass and a higher LFR, while maintaining stable fat percentage and BMI. These results indicate a shift toward a healthier body composition profile, potentially reflecting increased muscle function and activity levels as growth velocity improves."

Clinical • Genetic Disorders • Obesity • Orthopedics • FGFR3

Real-World Healthcare Utilization, Effectiveness, Health-Related Quality of Life, and Adherence to Vosoritide in Children with Achondroplasia in the United States (ACMG 2026) - P | "These interim results from an innovative real-world study demonstrate the healthcare impact of achondroplasia on children and their families and high vosoritide adherence in routine clinical practice. Effectiveness data align with real-world evidence from other geographies, and improvements in health-related quality of life outcomes, notably in physical function, underscore the importance of early treatment initiation to improve outcomes for children with achondroplasia."

Adherence • Clinical • HEOR • Real-world • Real-world evidence • Endocrine Disorders • Genetic Disorders • Musculoskeletal Diseases • Orthopedics • Otorhinolaryngology