In the final in a two-part series on the case for personalised gene therapy, pharmaceutical medical professional and patient advocate Dr Laura Issa discusses the opportunities of ensuring access to these rapidly emerging bespoke treatments. Dr Issa would like to acknowledge Nicholette (Nicky) Conway, the chair of Genetic Alliance Australia for providing an expert review of the series.
Unequivocally, yes, personalised gene therapy is ready for prime time.
Personalised or 'bespoke' gene therapy is a feasible treatment strategy for rare and ultra-rare genetic conditions that cannot otherwise be treated with approved pharmacotherapy, biologics or cell transplant and where there is a paucity of industry innovation.
We have the technology.
The advent of gene delivery technologies means no disease or tissue is off limits. Importantly, a toolbox of molecular gizmos can be matched to any genetic variation (point mutations, repeat expansions, insertions, deletions, rearrangement and copy number variations). This includes (non-exhaustive list) gene editing nucleases, base editing and exon splicing oligonucleotides, gene silencing oligonucleotides, and gene expression using plasmid DNA, messenger RNA and transfer RNA.
To varying extents, gene technologies have been validated in animal models, non-human primates (NHP) and humans. With the help of publicly available gene and protein atlases, it is possible to design a gene therapy strategy to match an individual’s genetic variant. Using the patient’s own cells, we can create organoids of any tissue type to test the therapy in the lab. There are labs across Australia that specialise in different types of patient-derived tissue organoids.
That’s the easy part.
A considerable amount of preclinical and animal experimentation is then required to demonstrate efficacy and safety and to establish a therapeutic dose before even starting a clinical trial. Australian academic labs and contractors have the capability to create animal models that recapitulate disease (e.g. genetically engineered zebrafish and mouse models).
A patient-led personalised design followed by testing in customised models increases the chances of success with treating, stopping or curing the disease and improves safety outcomes.
Whose responsibility is it to finance and do this work?
To quote Helen Clark, United Nations Development Programme (2009–2017)
"No country can claim to have achieved universal healthcare if it has not adequately and equitably met the needs of those with rare diseases," she said.
In a nation that prides itself on a world-class, universal healthcare system, is it the responsibility of the Government to ensure equitable access to therapy for every Australian, no matter how common or rare the condition?
Priority Action 2.4.1.2 of The National Strategic Action Plan for Rare Diseases (published 26 February 2020) commits Australia to building a National Health Genomics Policy Framework for the systematic, equitable and timely delivery of genomic services, including gene therapies for people living with a rare disease.
The Australian Genomics Priorities report (April 2024, p16) acknowledged the crucial role of substantial government funding in advancing gene therapy for ultra-rare diseases, that a sustainable nationally coordinated Australian clinical trials framework is needed, and that relying on industry partnerships may not suffice.
It is not clear how we are tracking towards achieving these national priorities.
Again, the US is well ahead of us with building a national framework. Launched in 2021, the Bespoke Gene Therapy Consortium (BGTC), backed by the Foundation for the NIH, has established platforms, standards, regulatory frameworks, and automated processes to speed the development and delivery of customised (bespoke) gene therapies for people affected by rare diseases. The Platform Vector Gene Therapy (PaVe-GT) project will achieve scale using the same gene delivery system and manufacturing methods across several rare disease gene therapy clinical trials. That is Brilliant!
Should Australia emulate this model? Whose job is it to make that happen? How do we decide which rare diseases to prioritise?
Australia is very well placed to leverage existing infrastructure to create a nationally coordinated capability, including world-renowned experts, investments in the genomics workforce, NCRIS (National Collaborative Research Infrastructure Strategy), local viral vector engineering and contract manufacturing facilities, and clinical trial centres.
What is the role of the newly formed Genomics Australia in this model?
Is it time to update the National Health Genomics Policy Framework to include a regulatory pathway for bespoke gene therapy?
As we kick off Genomics Australia Mark 2 on 1 July 2025, the timing is perfect to consider a Bespoke Gene Therapy Framework for Australia. It is time to take genomics out of the research setting and into clinical practice to fully realise the potential of genetic technologies and achieve universal access.
Again, we can take lessons from the US. In February 2024, BGTC published its first version of a regulatory framework, outlining the key steps and processes leading to regulatory approval for a first-in-human study. Brilliant again!
Adopting a personalised, precision medicine approach to treating rare genetic diseases is essential to upholding the noble ambition of universal access to healthcare for all Australians. Gene therapy using clinically validated delivery vehicles and gene modulators makes it possible.
Australia needs a national framework supported by a patient-led, patient-co-designed, public-private consortia.
This national collaboration network will link patient advocacy groups (e.g. Genetics Alliance Australia), research foundations, policymakers, Genomics Australia, academic societies and networks (e.g. HGSA, AFGN), clinical organisations, national facilities, contract manufacturers and industry in service of a common mission. Academics spearheading implementation science can help design the road map for clinical integration. A governance structure supported by clinical nodes with multidisciplinary teams will be required to support decision-making and prioritisation. There is capacity to scale, share and exchange the therapeutic constructs with other countries through network partnerships, such that N=1 becomes N=100+.
The cost-benefit ratio and economic benefits can be quantified, while the societal impacts will be immeasurable. Health budget offset will be realised, considering the lifetime cost of disease, dependency on allied health services and NDIS funding for devices, prostheses, and assistive technologies, etc. Improved mental health of patients would enhance community and workplace participation. Patients will realise their full academic and professional potential and live independently. Parents will hold on to the homes.
Personalised gene therapy is ready for prime time. It’s time to act because patients can’t wait, and it’s the right thing to do.
Five ways you can take action now:
- Exploring the topic and find out what government is doing for rare diseases HERE
- Share your opinion via LinkedIn.
- Get involved in shaping the future of Genomics Australia and the review the National Health Genomic Policy Framework by writing to the department (genomics@health.gov.au)
- Write to your Member of Parliament
- Advocate for rare genetic diseases within your professional and social communities.
EXTRA Bits:
The National Strategic Action Plan for Rare Diseases (26 February 2020) Priority Action 2.4.1.2 commits Australia to “Align with and build on the existing National Health Genomics Policy Framework for the systematic, equitable and timely delivery of genomic services, such as genetic testing (diagnostics) and gene therapies (treatments) and genetic counselling to Australians with, suspected of having, or with an increased chance of a rare disease.” It is not clear how we are achieving this.
The MRFF Clinical Trials Activity Initiative provides funding to attract trials sponsored by overseas innovators to Australia but does not specifically consider personalised, bespoke gene therapy trials.
The Life Saving Drugs Program (LSDP) is a must have - it pays for specific essential medicines to treat patients with ultra-rare and life-threatening diseases - provided there is an approved drug or biologic somewhere in the world that can be repurposed for that rare condition.
The Australian Genomics Priorities report (April 2024, p16) acknowledged the crucial role of substantial government funding in advancing gene therapy for ultra-rare diseases, that a sustainable nationally coordinated Australian clinical trials framework is needed, and that relying on industry partnerships may not suffice.
