On 2 August, 2021, the US Food and Drug Administration (FDA) approved a new drug, anifrolumab, for the treatment of systemic lupus erythematosus (SLE, or lupus). Remarkably, this is only the second drug approved for lupus in the past 60 years.
Why has this taken so long?
The answer is “it’s complicated”, as lupus is a complex and heterogeneous disease, making both molecular understanding, and the ability to measure treatment effects, difficult.
Importantly, the new drug is a potential game-changer for most of the 20,000 Australians affected by the disease, the majority of whom are women between the ages of 15 and 45. Until now, there’s been little specific treatment for the disease, and no cure.
Momentum towards breaking the impasse on new treatments for lupus has been building, and efforts at Monash have made major contributions to both the basic science and clinical measurement obstacles.
As a result of Monash’s world-class standing in the field, I was lucky enough to be the global chief investigator of the TULIP-2 trial of anifrolumab, the first positive phase 3 trial for a lupus drug in 10 years, and pivotal in the FDA approval granted in August.
All researchers are moved by a combination of curiosity and the identification of problems that need solving. As a clinician-scientist, the problems aren’t abstract, they’re right in front of you – and often there’s a pull between the job of helping real individuals with real diseases, and the job of working through science to solve those diseases once and for all.
For a clinician and a researcher, such a result is rare and enormously gratifying.
What is lupus?
Lupus is a form of rheumatic disease – autoimmune and inflammatory diseases that cause the immune system to attack your joints, muscles, bones and organs. However, while there have been great inroads in the treatment of some rheumatic diseases, such as rheumatoid arthritis, there’s been little progress for lupus.
The young women predominantly affected by lupus face drastic quality-of-life impacts and a shortened life span, and are still treated predominantly with drugs from the 1950s that have limited benefit and major side-effects.
The news from the US, and also from France, where the drug has been approved for use, gives hope to those who suffer from lupus.
Apart from the very real and hugely important benefit for the lupus patient, the FDA approval of this drug is also a big deal scientifically.
Anifrolumab targets the receptor for type I interferon (IFN), a protein that carries signals from the immune system to the tissues, resulting in inflammation and harm.
IFN has long been suspected of causing these symptoms in those with lupus, but only a clinical trial of a targeted therapy can tell for sure – and now we know. So not only did the trial results lead to approval of a drug that could bring relief to hundreds of thousands of people, it also validates a long-held belief that IFN has a role in the cause of lupus, and opens many, many doors to greater understanding of this disease.
A fast-working and effective treatment
From the clinical standpoint, it’s also a big deal.
Anifrolumab appears to work fast, and its effects are impactful and sustained. Although real-world experience will be key in learning its place in the model of care, there’s optimism that it could be the breakthrough for which the field has been looking for decades. Although there’s one previously FDA-approved targeted therapy for lupus, it’s had low uptake worldwide because of a slow onset of benefit, and it’s not listed on the PBS in Australia.
And there’s the rub. While it’s very exciting as a scientist to have been closely involved in the success of a trial leading to an FDA approval, the duality of my role as a clinician in Australia gives me pause.
The PBS is a world-standard system of drug pricing mechanisms that allows Australians access to good value for taxpayers’ money. However, it’s never previously approved a drug for lupus, and the complexities and nuances of this disease may make it hard for regulators to understand the value equation for Australian patients.
Therefore, even as the scientific field in which I work celebrates this milestone, I worry that in my clinical job I won’t be able to give my patients the good news that they, too, can access a potential breakthrough treatment for their disease. Time will tell.
Disclosure: Eric Morand has received funding from AstraZeneca as a consultant and for research support.
