#401 The First Precision Medicine for Achondroplasia with Dr. Ravi Savarirayan

Just a few years ago, there were no pharmacological treatments for patients with achondroplasia. Today, with multiple therapies on the market, the conversation has shifted from if we can treat to how we treat safely, consistently, and thoughtfully.

In this third and final installment of our achondroplasia series, sponsored by BioMarin, we explore the recently published international consensus guidelines for vosoritide. These guidelines provide a roadmap for the entire treatment lifecycle, from the initial diagnosis and counseling to initiation, monitoring, and eventually, the transition off therapy. You can review the prescribing information for vosoritide here with additional safety information, including about the risk of low blood pressure.

Joining us in-person all the way from Australia is the lead author of these guidelines, Dr. Ravi Savarirayan. Dr. Savarirayan is a global leader in skeletal dysplasia and has been a driving force in the clinical development of vosoritide from its earliest stages.

Topics Discuss:

The Journey of Vosoritide: Dr. Savarirayan shares his personal "why", from the early research phases to the clinical trials that changed the landscape of skeletal dysplasia care.

Precision Medicine at the Molecular Level: How vosoritide acts as the first precision medicine approved for achondroplasia by targeting and counteracting overactive FGFR3 signaling, along with important safety information such as a risk for low blood pressure

The International Guidelines: Why a global consensus was necessary and how it addresses gaps in real-world clinical practice.

The Treatment Lifecycle:

• Counseling: Setting expectations and having the first conversation with families.

• Initiation: Practical tips for daily subcutaneous injections and establishing a routine.

• Safety & Monitoring: How clinicians monitor growth and manage safety considerations like hypotension across different age groups.

• Discontinuation: How to navigate growth plate closure and the transition off therapy.

The Future of Care: How these guidelines will evolve as we gather more long-term, real-world data.

Our Guest Dr. Ravi Savarirayan:

Ravi Savarirayan is consultant clinical geneticist at Victorian Clinical Genetics Services, Professorial fellow at the University of Melbourne, and Group leader (Molecular Therapies at Murdoch Children’s Research Institute, Victoria, Australia.

Professor Savarirayan received his MBBS from the University of Adelaide, Australia in 1990 and became a Fellow of the Royal Australasian College of Physicians in 1997. He was certified as a specialist in Clinical Genetics by the Human Genetics Society of Australasia in 1998 and was awarded his Doctor of Medicine from the University of Melbourne in 2004. He was awarded the Fulbright Professional Scholarship for Australia in 1998, and took this up at University of California, Los Angeles (UCLA).

Professor Savarirayan’s primary research focus is on inherited disorders of the skeleton causing short stature, arthritis, and osteoporosis. He has published over 230 peer-reviewed articles and received over $35M in research funding, collaborating with researchers from 40 countries.

His current clinical trial activities are pioneering disruptive new therapies for the treatment of genetic disorders. He was the global lead investigator of the clinical development program that identified vosoritide as the first precision therapy for children with achondroplasia. He was recently named one of the 30 “Brilliant minds” of the Murdoch Children’s Research Institute over the past 30 years, was awarded the Institute’s research excellence award in 2020, and is an NHMRC Leadership Fellow.

Summary:

We talk about the journey to vosoritide, Dr. Ravi’s personal history with achondroplasia research, published treatment guidelines and how vosoritide is approved under accelerated approval to increase linear growth in pediatric patients with achondroplasia with open epiphyses. We also discuss the most serious side effect seen—transient decreases in blood pressure, which is why patients should have adequate food and fluid intake prior to administration. We also cover that it is a daily injection and that injection site reactions are the most common side effect and some patients also experienced vomiting, injection site urticaria, arthralgia, decreased blood pressure, and gastroenteritis. Those aren't all the side effects, so please refer to the prescribing information here for more information about vosoritide.

Relevant Resources:

Savarirayan, R., Hoover-Fong, J., Ozono, K. et al. International consensus guidelines on the implementation and monitoring of vosoritide therapy in individuals with achondroplasia. Nat Rev Endocrinol 21, 314–324 (2025). https://doi.org/10.1038/s41574-024-01074-9

Here is a list of Dr. Ravi Savarirayan’s publications, there are far too many to list them all here.

Dr. Ravi Savarirayan Video Explaining Vosoritide

Relevant DNA Today Episodes:

• #192 Osteogenesis Imperfecta with The Middle’s Atticus Shaffer

• #301 Dwarfism with Colleen Gioffreda

• #348: NIPT Beyond the Basics: Screening for Single-Gene Conditions (including skeletal dysplasia disorders)

• #359 Breaking Down Achondroplasia: A Pediatrician in Clinical Genetics Explains (Biomarin’s Sponsored Series First Installment)

• #385 Inside ACMG 2026: How AI and New Tools Enhance Genome Sequencing and Equity

• #386 Achondroplasia Beyond Height: Managing Lifelong Medical Needs (Biomarin’s Sponsored Series Second Installment)

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