Embracing science to shift treatment paradigms in autoimmune disease

A new age of innovation in immunology could change medical practice and people’s lives, as long as all parts of the system learn, evolve and work together, writes Anant Murthy, General Manager, argenx (EBR: ARGX) EMEA, in an Expert View piece.

Scientific discoveries are advancing a new era of medical possibilities for people with autoimmune disorders. We are seeing a growing number of highly targeted medicines that are aimed at keeping the immune system in check thanks to an improved understanding of the biology behind conditions that trigger the body’s own immune system to turn on itself.

For many years, immunology related to autoimmune diseases has been a poorly understood area of medicine, but it’s now attracting considerable interest from researchers in academia and industry alike thanks to a deepening knowledge of disease biology.

Increased understanding of disease biology

Take immunoglobulin G (IgG) antibodies for example. IgG antibodies are normally produced to fight infections, but they can also attack our own cells and tissues. These so-called autoantibodies can result in a number of autoimmune disorders, including hematological, neurological and rheumatological conditions.

We have discovered that IgG autoantibodies can remain in circulation because they are being recycled by the neonatal Fc receptor (FcRn).

This increased understanding of disease biology is allowing argenx and other biotech companies to develop medicines that block IgG recycling by FcRn and may result in new treatment options for people with chronic autoimmune conditions, such as generalized myasthenia gravis (gMG), a debilitating and sometimes life-threatening condition.

These scientific advances have led to the development of efgartigimod, which is able to bind to FcRn protein receptors and block the recycling of IgG autoantibodies, leading instead to their degradation by lysosomes – intracellular organelles in our body containing enzymes that break down proteins and other macromolecules. This reduces the amount of circulating IgG autoimmune antibodies, thereby reducing the symptoms of IgG-mediated autoimmune diseases.

Efgartigimod, which was first approved for use in the UK in 2023, offers clinicians and people with gMG a new targeted treatment that avoids the widespread immunosuppression often seen with today’s standard-of-care treatments. Rather than wiping out all immune cells, this advancement has enabled a specific focus on those antibodies causing disease.

As researchers uncover more about the functioning of our complex immune systems, we are hopeful that the arrival of novel targeted medicines could radically alter treatment paradigms and outcomes for patients.

Significant healthcare impact

Over the last 30 years, there have been very few, if any, new medicines for people with autoimmune conditions, such as gMG. Therapeutic approaches have been based on non-specific pharmacological strategies, such as steroids. Although they have provided some relief, they can be associated with burdensome and serious adverse events, such as diabetes, hypertension and osteoporosis.

People living with autoimmune diseases have to cope with a range of symptoms, from fatigue to digestive issues and recurring fever, that can make it difficult for them to take part in daily activities or to continue working.

It is estimated that two-thirds of people with autoimmune diseases are forced to stop working because of their conditions, putting individual household budgets under pressure and resulting in productivity losses for the broader economy.

And the number of people with autoimmune diseases is on the rise. A study recently published in The Lancet that looked at the electronic health records of 22 million people in the UK, showed that autoimmune disorders are now affecting 10% of the population, higher than earlier estimates that were based on smaller sample sizes.1

The potential impact of this on the healthcare system as well as the broader societal implications could be significant. For instance, autoimmune diseases are a leading cause of death among females in the UK, according to a large study of UK health records.2

Collaborative input required

It is crucial that all parts of the system keep pace with the latest scientific developments so that new medicines reach the patients who need them. I believe we have what it takes to be successful, but it will require innovative thinking as well as open and collaborative dialogue – from everyone.

There are encouraging signs. Government agencies such as the Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Health and Care Excellence (NICE) in the UK have both committed to speeding up regulatory and reimbursement processes so that patients can get access to new medicines more quickly.

The MHRA has introduced a sovereign national licensing route in addition to recognizing the regulatory decisions of other leading agencies, such as the Food and Drug Administration (FDA) in the USA. The NICE intends to speed-up appraisal timelines by 15% this year, in part by optimizing their processes and taking a more pragmatic and proportionate approach to some evaluations.

These are important commitments that are aimed at ensuring innovation is not left sitting on the shelf or made accessible only to a few when many could benefit.

At argenx, we have been working closely with NICE to meet its evidence requirements and to ensure we find workable solutions that will enable patients to potentially benefit.

Like others, we have found that the path to access isn’t always easy. There are challenges and tough realities to face on both sides; however, what ultimately matters is that we have a shared resolve to find solutions that are sustainable and potentially transformative for patients. If we keep that as a central dogma, new and innovative access solutions will emerge – solutions that will help us match the speed of scientific innovation.

People with autoimmune conditions have been waiting for new treatment options for too long. Scientific advances in immunology have the potential to change lives on an individual and societal level. Now that the science has arrived, we must do all we can to ensure it moves rapidly through all parts of the health system and into the clinic without further delay.

References

1 Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK - The Lancet

2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951969/