Molecular Therapies
To improve current and future health outcomes in children with skeletal disorders by conducting clinical trials utilising new precision therapies.
Prof Ravi Savarirayan leads the Molecular Therapies research group and is a Professorial Fellow at the University of Melbourne, and Consultant Clinical Geneticist at Victorian Clinical Genetics Services. He is a clinical geneticist, and translational scientist with bench-to-bedside expertise in genetic disorders of the skeleton.
Skeletal dysplasia is an individually rare, but collectively common musculoskeletal disorders caused by impaired development, growth, and maintenance of the human skeleton. Individuals impacted by these conditions experience a variety of medical complications, functional limitations, and psychosocial challenges across their lifespan. Treatment options for these conditions are limited, with poor outcomes. However, recent advances in genetic technologies have allowed us to better understand the mechanisms underlying these conditions. This has revealed drug targets to treat these conditions at their very source (precision medicine).
We focus research on translational outcomes of basic/clinical research, such as clinical drug trials, natural history studies, and best practice guidelines for management based on current evidence.
We aim to understand the molecular basis of these disorders to improve diagnosis and counselling, identify new therapeutic targets, and test the effectiveness of new treatments to improve the quality of life for children with these conditions.
Group Leaders
Group Members
Our projects
Commercially sponsored clinical trials
- 111-202: A Phase 2 Study of BMN 111 to Evaluate Safety, Tolerability, and Efficacy in Children With Achondroplasia (ACH)
- 111-205: A Phase 2, Open-Label, Extension Study to Evaluate the Long-Term Safety, Tolerability and Efficacy of BMN111 in Children with Achondroplasia
- 111-301: A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicentre Study to Evaluate the Efficacy and Safety of BMN 111 in Children with Achondroplasia
- 111-302: A Phase 3, Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children with Achondroplasia
- 111-206: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children with Achondroplasia, Age 0 to < 60 Months
- 111-208: A Phase 2 Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children with Achondroplasia
- 111-209: A randomized, controlled, open-label clinical trial with an open-label extension to investigate the safety of vosoritide in infants and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery.
- ACcomplisH: A Phase 2, multicentre, double-blind, randomized, placebo-controlled, dose escalation trial evaluating safety, efficacy, and pharmacokinetics of subcutaneous doses of TransCon CNP administered once weekly for 12 months in prepubertal children with achondroplasia
- PROPEL 2: Phase 2, Open-Label, Dose-Escalation and Dose-Expansion Study of Infigratinib, an FGFR 1-3-Selective Tyrosine Kinase Inhibitor, in Children with Achondroplasia
- PROPEL OLE: Phase 2, Open-Label, Long-Term, Extension (OLE) Study of Infigratinib, an FGFR 1-3-Selective Tyrosine Kinase Inhibitor, in Children with Achondroplasia
- Silverbird: A Phase 2 Multiple Dose, Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Recifercept in Children with Achondroplasia
- INCB 00928-201: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of INCB000928 in Participants With Fibrodysplasia Ossificans Progressiva
- ION373-CS1: A Phase 1-3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION373 in Patients with Alexander Disease
Natural history studies
- 111-901: A Multicenter, Multinational Clinical Assessment Study for Pediatric Patients With Achondroplasia – natural history study
- ACHieve: A multi-center, longitudinal, observational study of children with Achondroplasia
- Propel 1: Prospective clinical assessment study in children with achondroplasia
- Dreambird: An International, Prospective Registry Investigating The Natural History Of Children With Achondroplasia
Research grants (EU Horizon 2020)
- MCDS Therapy: An open label phase I/IIa trial repurposing carbamazepine (CBZ) for the treatment of skeletal dysplasia in children
Research projects
- Barriers and facilitators to continued participation in a long term high burden clinical drug trial for achondroplasia
- Exploring the child and family experience of children aged 2-4 years receiving daily subcutaneous vosoritide injections: A pilot study.
Funding
- European Union Horizon 2020 grant
Collaborations
- Biomarin Pharmaceutical Inc
- Ascendis Pharma A/S
- QED Therapeutics
- Pfizer
- Incyte
- Ionis Pharmaceuticals
Featured publications
- C-type natriuretic peptide analogue therapy in children with achondroplasia.
N Engl J Med 2019; 381:25-35. Savarirayan R, Irving M, Bacino CA, Bostwick B, Charrow J, Cormier-Daire V, et al. - Once daily subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial.
Lancet 2020; 396:684-92. Savarirayan R, Tofts L, Irving M, Wilcox W, Bacino CA, Hoover-Fong J, et al. - Lifetime impact of achondroplasia: current evidence and perspectives on natural history.
Bone 2021; doi: 10.1016/j.bone.2021.115872. Hoover-Fong J, Cheung MS, Fano V, Hagenas L, Hecht JT,..Savarirayan R. - International Consensus Statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia.
Nat. Rev. Endocrinol 2021. doi:10.1038/s41574-021-00595-x. Savarirayan R, Ireland P, Irving M, Thompson D, Alves I, Baratela WAR, et al. - Best practice guidelines regarding prenatal evaluation and delivery of patients with skeletal dysplasia.
Am J Obstet Gynecol 2018;219(6):545-562. Savarirayan R, Rossiter JP, Hoover-Fong JE, et al.