Almost 4 decades of pivotal Breakthrough T1D research funding, strategic industry investment, and powerful government advocacy, have culminated in the arrival of the first disease-modifying therapy for type 1 diabetes (T1D) in Australia.
Tzield, the brand name of the drug teplizumab, was recently registered by the Therapeutics Goods Administration (TGA) in Australia to delay the progression of T1D in people in the early stages of the condition. This landmark moment would not have happened without Breakthrough T1D – read on to learn why.
Funding the development and testing of teplizumab
It began in 1988 when Breakthrough T1D (then JDRF) awarded a career development grant to a budding US researcher called Kevan Herold. Kevan had been diagnosed with T1D in 1974, which inspired him to become an immunologist dedicated to developing a drug to prevent T1D. Since then, Kevan (now Professor Kevan Herold) has received more than 15 research grants from Breakthrough T1D to develop and test whether teplizumab can delay the progression of T1D – the first step in the quest for prevention.
In 1997, Breakthrough T1D awarded Professor Jeff Bluestone, a US-based immunologist, the first of many grants to develop teplizumab alongside Professor Herold. The two researchers used this crucial funding to collaborate on research to better understand the biological pathways targeted by teplizumab and fine-tune the drug. Professor Herold led 6 clinical trials exploring its effectiveness and safety. In 2002, he published the first evidence that teplizumab could slow the development of T1D in people newly diagnosed. His subsequent trials tested the drug in more people and those at an earlier stage of T1D development, revealing teplizumab’s ability to preserve insulin production with minimal side effects.
International effort enabled by government support
But it wasn’t just through direct investment that Breakthrough T1D helped to fund teplizumab’s journey. In the late 1990s, huge advocacy efforts involving hundreds of Breakthrough T1D supporters lobbying US politicians resulted in the US government announcing the Special Diabetes Program in 1997. This initially involved dedicating $30m per year to T1D research through the National Institutes of Health (NIH), the national medical research agency for the US. This was increased to $100m and later $170m, thanks to dedicated Breakthrough T1D advocates in the US.
Through the Special Diabetes Program, TrialNet was launched in 2001. TrialNet is an international network of T1D researchers and healthcare teams, which provided a global boost to clinical trial capability. It provided funding to establish international screening initiatives to identify people in the early stages of T1D and fast-track them into clinical trials of therapies to slow the progression of T1D. This enabled researchers in around the world to gather evidence of the effectiveness of teplizumab on a global scale and unlock access to the drug in countries like Australia.
In Australia, Breakthrough T1D’s Type 1 Diabetes Clinical Research Network, funded by the Australian Government, supports multiple screening and monitoring initiatives, with the long-term goal of a national T1D screening program. This would ensure those who could be eligible for Tzield are identified. Breakthrough T1D also deliver a clinical trials platform called the Australasian Type 1 Diabetes Immunotherapy Collaborative (ATIC), which aims to connect all people diagnosed with T1D to a clinical trial. Already, ATIC has more than doubled the number of T1D clinical trials in Australia, connecting people to T1D studies and clinical trials testing disease modifying therapies, like Tzield.
In 2011, TrialNet launched a clinical trial testing if teplizumab could delay the progression from stage 2 T1D, where the condition has begun but before symptoms develop, to stage 3 T1D, where insulin treatment is needed. Breakthrough T1D also contributed funding for the ambitious trial, which was called TN-10, and again led by Professor Herold. The investment in Australian screening and clinical trials initiatives (through ATIC) enabled Australians to be part of TN-10, and future clinical trials of teplizumab. In 2019, Professor Harold shared landmark data from TN-10 showing that teplizumab could delay the onset of stage 3 T1D by an average of 2 years.
Backing pharmaceutical companies
Not-for-profit organisations like Breakthrough T1D, and even entire governments, don’t have enough money to get a drug like teplizumab into the hands of people living with T1D. So, Breakthrough T1D strategically invests in pharmaceutical companies through a venture philanthropy fund called the T1D Fund.
In 2005, Professor Herold and Dr Bluestone sold teplizumab to a small company called MacroGenics, which Breakthrough T1D awarded a 5-year Industry Discovery and Development Program grant the following year.
In 2017, Breakthrough T1D invested in another small company called Provention Bio, which helped them to acquire teplizumab and set up a large clinical trial, led by Professor Herold once more. That key investment has helped catalyse hundreds of millions of dollars to get teplizumab, which at this stage was officially named Tzield, out of the research landscape and into the real world. Provention Bio was later acquired by a larger pharmaceutical company called Sanofi. These two companies had the means to push Tzield over the finish line.
Getting Tzield to the people who need it
After all of this collective work and the progress from Professor Herald and Dr Bluestone, finally, Tzield was ready to be submitted to the US Food and Drug Administration (FDA) for review. 100 years after the discovery insulin, it became the first new therapy for T1D, officially approved by the FDA in 2022 for people aged 8 and older with stage 2 T1D. This was a significant moment in the history of T1D and marked a new era – moving from treatment to delay.
Since then, regulatory bodies across the world have followed, including the Therapeutic Goods Administration (TGA) in Australia most recently.
When the FDA approved teplizumab, Professor Herold said: “The story with the clinical use of teplizumab began with a Breakthrough T1D grant to support a trial in patients with new onset type 1 diabetes. The success of this initial study planted a seed that led to further studies and support from the NIH. The [FDA’s] decision represents a turning point in the field.”
Expanding access in Australia
Approval by the TGA is the crucial starting point for Tzield to become widely available in Australia, but broader access to the medication is dependent on it being listed on the Pharmaceutical Benefits Scheme (PBS), which comprises medications that are subsidised by the Australian Government.
Sanofi has already submitted the therapy to be considered by the Pharmaceutical Benefits Advisory Committee (PBAC), which makes recommendations to the Government on what should be listed on the PBS.
Breakthrough T1D, with support from the wider T1D community, is advocating for this, to ensure Australians have access to this groundbreaking therapy. We hope that Tzield’s listing on the PBS will be the next update we can provide.
Breakthrough T1D is incredibly proud of how far teplizumab has come since 1988, but we will not stop until everyone who could benefit from this lifechanging drug can access it.