Molecular Therapies Research

The Molecular Therapies research group at MCRI is dedicated to improving health outcomes for children with skeletal disorders through clinical trials of innovative precision therapies.

Led by Professor Ravi Savarirayan, a clinical geneticist and translational scientist, the group focuses on genetic disorders of the skeleton, known as skeletal dysplasias.

While individually rare, these conditions are collectively common and can cause significant medical, functional, and psychosocial challenges throughout life.

Historically, treatment options have been limited and outcomes poor. However, advances in genetic technologies have deepened our understanding of the molecular mechanisms behind these disorders. This has opened the door to precision medicine, where therapies target the root causes of disease.

Our research goals

We aim to:

• improve diagnosis and genetic counselling
• identify new therapeutic targets
• evaluate the safety and effectiveness of emerging treatments
• enhance quality of life for children living with skeletal dysplasias
• help to manage the nutrition of children with skeletal dysplasia
• advance allied health research in children with skeletal dysplasia conditions

Our methodologies

Our research spans:

• clinical drug trials
• natural history studies
• development of best-practice guidelines
• translation of evidence based research into clinical practice

Contact us

Dr Supriya Raj
Team Leader/Senior Research Coordinator, Molecular Therapies
Email: show email address
Phone: show phone number  

Research projects

1. Clinical outcomes following prescription of Vosoritide in children with Achondroplasia 0-2 years of age.
   
   
2. Does education in positive parental behaviour during needle procedures improve the response of children with ACH to subcutaneous injections?
   
   

Ongoing commercially sponsored clinical trials

Biomarin pharmaceutical trials

BioMarin is a global biotechnology company that has developed medicines to treat conditions such as achondroplasia, severe hemophilia A, and several rare diseases. 

• 111-205: A Phase 2, Open-Label, Extension Study to Evaluate the Long-Term Safety, Tolerability and Efficacy of BMN111 in Children with Achondroplasia.
• 111-302: A Phase 3, Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children with Achondroplasia.
• 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.
• 111-303: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vosoritide in Children with Hypochondroplasia.
• 111-210: A Phase 2, Randomised, Controlled, Multicentre Study of Vosoritide in Children with Idiopathic Short Stature.
• 111-211: A Phase 2, Randomized, Human Growth Hormone-Controlled, Multicenter, Basket Study of Vosoritide in Children with Turner Syndrome, Short Stature Homeobox-Containing Gene Deficiency, and Noonan Syndrome with an Inadequate Response to Human Growth Hormone.
• 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.
• 111-308: A Phase 3, Open-Label, Long-Term Extension Study to Evaluate the Safety and Efficacy of Vosoritide in Children with Hypochondroplasia.
  
  

Ascendis Pharma trials 

Ascendis Pharma is a global biopharmaceutical company. They use innovative TransCon® technology platform to develop new therapies that demonstrate best-in-class potential to improve treatment safety, efficacy, tolerability, and convenience.

• ApproaCH: A Phase 2b, Multicenter, Double-Blind, Randomized, Placebo-controlled Trial evaluating Efficacy and Safety of Subcutaneous Doses of TransCon CNP Administered Once Weekly for 52 Weeks in Children with Achondroplasia followed by an Open Label Extension period.
• AttaCH: A Phase 2, Multicenter, Long-Term, Open Label Extension Trial, Evaluating Safety, Tolerability, and Efficacy of Subcutaneous Doses of TransCon CNP Administered Once Weekly in Children and Adolescents with Achondroplasia.
• reACHin: A Phase 2, Multicenter, Double-Blind, Randomized, Placebo-controlled Trial,evaluating Safety, Tolerability, and Efficacy of Subcutaneous Doses of TransCon CNP Administered Once Weekly for 52 Weeks in Infants (0 to <2 years of age) with Achondroplasia followed by an Open Label Extension (OLE) period.
  
  

QED Therapeutics trials

QED clinical program includes multiple achondroplasia clinical trials that are designed to better understand FGFR3-driven skeletal dysplasias and to evaluate an oral investigational therapy option for these conditions.

• Propel 3: A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Infigratinib in Children 3 to 18 Years of Age 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.
• Propel I& T- Phase 2b, Randomized, Double-Blind, Placebo-Controlled Clinical Trial, Preceded by a Single Ascending Dose Portion and a Phase 2 Open-Label Portion, to Evaluate the Safety and Efficacy of Oral Infigratinib in Infants and Young Children with Achondroplasia.
• Accel 2/3- A Phase 2/3, Multicentre, open-label, Phase followed by a Double-blind, Randomised, Placebo-controlled Study to Evaluate the Efficacy and Safety of Infigratinib in Children with Hypochondroplasia.
  
  

Incyte Biopharmaceutical Corporation trials 

Incyte is a global biopharmaceutical company focused on finding innovative solutions for serious unmet medical needs.

• A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of INCB000928 in Participants With Fibrodysplasia Ossificans Progressiva (PROGRESS).
  
  

Tyra Biosciences trials

TYRA is a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in FGFR biology Tyra is working to advance BEACH301, a clinical study of TYRA-300 for children with achondroplasia.

• A Multicenter, Phase 2, Dose-Escalation/Dose-Expansion Study of TYRA-300 in Children with Achondroplasia with Open Growth Plates: BEACH301.
  
  

Natural history studies

These are preplanned observational study intended to track the course of the disease.

• 111-902: A Multicenter Multinational Observational Study of Children with Hypochondroplasia.
• Accel- Prospective Clinical Assessment Study in Children with Hypochondroplasia.

Funding

Thank you to our supporters

• European Union Horizon 2020 grant
• National Health and Medical Research Council (NHMRC)

Collaborations

We partner with leading institutions worldwide, including:

• Biomarin Pharmaceutical Inc
• Ascendis Pharma A/S
• QED Therapeutics
• Pfizer
• Incyte
• Sanofi
• Tyra Pharmaceuticals
• Alexion

Featured publications

Savarirayan R, Irving M, Bacino CA, Bostwick B, Charrow J, Cormier-Daire V, Le Quan Sang KH, Dickson P, Harmatz P, Phillips J, Owen N, Cherukuri A, Jayaram K, Jeha GS, Larimore K, Chan ML, Huntsman Labed A, Day J, Hoover-Fong J. C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia. N Engl J Med. 2019 Jul 4;381(1):25-35. doi: 10.1056/NEJMoa1813446. Epub 2019 Jun 18. PMID: 31269546.

Savarirayan R, Tofts L, Irving M, Wilcox W, Bacino CA, Hoover-Fong J, Ullot Font R, Harmatz P, Rutsch F, Bober MB, Polgreen LE, Ginebreda I, Mohnike K, Charrow J, Hoernschemeyer D, Ozono K, Alanay Y, Arundel P, Kagami S, Yasui N, White KK, Saal HM, Leiva-Gea A, Luna-González F, Mochizuki H, Basel D, Porco DM, Jayaram K, Fisheleva E, Huntsman-Labed A, Day J. Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. 2020 Sep 5;396(10252):684-692. doi: 10.1016/S0140-6736(20)31541-5. Erratum in: Lancet. 2020 Oct 10;396(10257):1070. doi: 10.1016/S0140-6736(20)32074-2. PMID: 32891212.

Savarirayan R, Tofts L, Irving M, Wilcox WR, Bacino CA, Hoover-Fong J, Font RU, Harmatz P, Rutsch F, Bober MB, Polgreen LE, Ginebreda I, Mohnike K, Charrow J, Hoernschemeyer D, Ozono K, Alanay Y, Arundel P, Kotani Y, Yasui N, White KK, Saal HM, Leiva-Gea A, Luna-González F, Mochizuki H, Basel D, Porco DM, Jayaram K, Fisheleva E, Huntsman-Labed A, Day JRS. Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study. Genet Med. 2021 Dec;23(12):2443-2447. doi: 10.1038/s41436-021-01287-7. Epub 2021 Aug 2. PMID: 34341520; PMCID: PMC8327889.

Ireland PJ, Savarirayan R, Pocovi T, Tate T, Coussens M, Tofts L, Munns C, Pacey V. Development of the Screening Tool for Everyday Mobility and Symptoms (STEMS) for skeletal dysplasia. Orphanet J Rare Dis. 2021 Jan 21;16(1):40. doi: 10.1186/s13023-021-01681-z. PMID: 33478535; PMCID: PMC7818550.

Savarirayan R, Ireland P, Irving M, Thompson D, Alves I, Baratela WAR, Betts J, Bober MB, Boero S, Briddell J, Campbell J, Campeau PM, Carl-Innig P, Cheung MS, Cobourne M, Cormier-Daire V, Deladure-Molla M, Del Pino M, Elphick H, Fano V, Fauroux B, Gibbins J, Groves ML, Hagenäs L, Hannon T, Hoover-Fong J, Kaisermann M, Leiva-Gea A, Llerena J, Mackenzie W, Martin K, Mazzoleni F, McDonnell S, Meazzini MC, Milerad J, Mohnike K, Mortier GR, Offiah A, Ozono K, Phillips JA 3rd, Powell S, Prasad Y, Raggio C, Rosselli P, Rossiter J, Selicorni A, Sessa M, Theroux M, Thomas M, Trespedi L, Tunkel D, Wallis C, Wright M, Yasui N, Fredwall SO. International Consensus Statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia. Nat Rev Endocrinol. 2022 Mar;18(3):173-189. doi: 10.1038/s41574-021-00595-x. Epub 2021 Nov 26. PMID: 34837063.

Savarirayan R, De Bergua JM, Arundel P, McDevitt H, Cormier-Daire V, Saraff V, Skae M, Delgado B, Leiva-Gea A, Santos-Simarro F, Salles JP, Nicolino M, Rossi M, Kannu P, Bober MB, Phillips J 3rd, Saal H, Harmatz P, Burren C, Gotway G, Cho T, Muslimova E, Weng R, Rogoff D, Hoover-Fong J, Irving M. Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies. Ther Adv Musculoskelet Dis. 2022 Mar 21;14:1759720X221084848. doi: 10.1177/1759720X221084848. PMID: 35342457; PMCID: PMC8941703.

Savarirayan R, Hoernschemeyer DG, Ljungberg M, Zarate YA, Bacino CA, Bober MB, Legare JM, Högler W, Quattrin T, Abuzzahab MJ, Hofman PL, White KK, Ma NS, Schnabel D, Sousa SB, Mao M, Smith A, Chakraborty M, Giwa A, Winding B, Volck B, Shu AD, McDonnell C. Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial. EClinicalMedicine. 2023 Oct 2;65:102258. doi: 10.1016/j.eclinm.2023.102258. PMID: 37823031; PMCID: PMC10562841.

Savarirayan R, Wilcox WR, Harmatz P, Phillips J 3rd, Polgreen LE, Tofts L, Ozono K, Arundel P, Irving M, Bacino CA, Basel D, Bober MB, Charrow J, Mochizuki H, Kotani Y, Saal HM, Army C, Jeha G, Qi Y, Han L, Fisheleva E, Huntsman-Labed A, Day J. Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Child Adolesc Health. 2024 Jan;8(1):40-50. doi: 10.1016/S2352-4642(23)00265-1. Epub 2023 Nov 18. PMID: 37984383.

Dentry T, O'Neill J, Raj S, Gardiner K, Savarirayan R. Exploring the family experience of children aged 2-4 years receiving daily vosoritide injections: A qualitative study. J Pediatr Nurs. 2024 Jul-Aug;77:e167-e176. doi: 10.1016/j.pedn.2024.04.007. Epub 2024 Apr 10. PMID: 38604940.

Savarirayan R, Irving M, Wilcox WR, Bacino CA, Hoover-Fong JE, Harmatz P, Polgreen LE, Mohnike K, Prada CE, Kubota T, Arundel P, Leiva-Gea A, Rowell R, Low A, Sabir I, Huntsman-Labed A, Day J. Persistent growth-promoting effects of vosoritide in children with achondroplasia are accompanied by improvements in physical and social aspects of health-related quality of life. Genet Med. 2024 Dec;26(12):101274. doi: 10.1016/j.gim.2024.101274. Epub 2024 Sep 18. PMID: 39305160.

Savarirayan R, Irving M, Harmatz P, Delgado B, Wilcox WR, Philips J, Owen N, Bacino CA, Tofts L, Charrow J, Polgreen LE, Hoover-Fong J, Arundel P, Ginebreda I, Saal HM, Basel D, Font RU, Ozono K, Bober MB, Cormier-Daire V, Le Quan Sang KH, Baujat G, Alanay Y, Rutsch F, Hoernschemeyer D, Mohnike K, Mochizuki H, Tajima A, Kotani Y, Weaver DD, White KK, Army C, Larrimore K, Gregg K, Jeha G, Milligan C, Fisheleva E, Huntsman-Labed A, Day J. Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study. Genet Med. 2022 Dec;24(12):2444-2452. doi: 10.1016/j.gim.2022.08.015. Epub 2022 Sep 16. PMID: 36107167.

Savarirayan R, De Bergua JM, Arundel P, Salles JP, Saraff V, Delgado B, Leiva-Gea A, McDevitt H, Nicolino M, Rossi M, Salcedo M, Cormier-Daire V, Skae M, Kannu P, Phillips J 3rd, Saal H, Harmatz P, Candler T, Hill D, Muslimova E, Weng R, Bai Y, Raj S, Hoover-Fong J, Irving M, Rogoff D. Oral Infigratinib Therapy in Children with Achondroplasia. N Engl J Med. 2025 Feb 27;392(9):865-874. doi: 10.1056/NEJMoa2411790. Epub 2024 Nov 18. PMID: 39555818.

Savarirayan R, Hoover-Fong J, Ozono K, Backeljauw P, Cormier-Daire V, DeAndrade K, Ireland P, Irving M, Llerena Junior J, Maghnie M, Menzel M, Merchant N, Mohnike K, Iruretagoyena SN, Okada K, Fredwall SO. International consensus guidelines on the implementation and monitoring of vosoritide therapy in individuals with achondroplasia. Nat Rev Endocrinol. 2025 May;21(5):314-324. doi: 10.1038/s41574-024-01074-9. Epub 2025 Jan 6. PMID: 39757323.

Buciek LH, Jacobsen JR, Raj S, Adams AM, Vandeleur M, Hove HB, Buchwald CV, Kiaer EK, Griffiths A, Savarirayan R. Sleep-disordered breathing in children with achondroplasia assessed by polysomnography: a retrospective chart review. Arch Dis Child. 2025 Jul 17:archdischild-2025-328595. doi: 10.1136/archdischild-2025-328595. Epub ahead of print. PMID: 40675782.