Developing and commercialising a non-invasive test of adrenal insufficiency for children on steroids.

The adrenal glands sit above the kidneys and are part of the body's endocrine system and produce the vital stress hormone cortisol. Adrenal insufficiency (AI) is the inability of the body to produce adequate cortisol levels and, untreated, leads to circulatory collapse and death through adrenal crisis. Diagnosis of AI is frequently missed due to non-specific symptoms.

Causes of AI in UK include Addison's disease (adrenalitis), brain tumours and adrenal suppression from steroid medication for inflammatory conditions (e.g. arthritis, asthma, cancers). Globally major causes are TB and AIDS. AI is usually permanent but in patients taking steroid medication, it may be temporary necessitating repeated testing.

Concern about AI related to steroid use is rising, with widespread prescription of potent steroids in all medical specialties and recognition that all steroids can cause AI. In August 2020 the NHS National Patient Safety Agency released an alert for UK healthcare organisations to issue Steroid Emergency Cards to all patients at risk of AI, including those on inhaled steroids.

Nearly half a million UK children are prescribed inhaled steroids (preventers) for asthma, many on doses exceeding recommendations.

The Short Synacthen Test (SST) is the most popular diagnostic test for AI worldwide. Synacthen stimulates the adrenal glands to produce cortisol. Blood tests are taken before Synacthen is given and 30-60 minutes after in order to measure the rise in cortisol.

The SST is invasive, requiring intravenous cannulation and blood sampling, and resource-intensive due to the need for skilled personnel and a hospital day-care admission. This leads to raised thresholds for investigation and delayed diagnosis, especially in children, putting patients at risk of adrenal crisis. The practical challenge is identifying, diagnosing and treating patients suffering from steroid excess and AI.

Dr Elder has undertaken fundamental work developing a new non-invasive test for AI, "The Nasacthin Test", with the drug, tetracosactide (Synacthen), given via a nasal spray and the resultant cortisol response measured on saliva samples. This will enable the investigation of children at home or in clinic, without requirement for hospital attendance and blood sampling.

The new drug is a combination of tetracosactide with chitosan, a nasal drug enhancer, which aids absorption from the nose into the bloodstream. To date the team have completed five pilot clinical trials testing different doses and formulations (mixtures) and found the new drug, Nasacthin, to be reliably absorbed and well tolerated in children. The non-invasive Nasacthin test will allow early diagnosis, prevent adrenal crisis and help paediatricians understand the burden of disease created by steroids.

The challenge is creating a clinical development plan and commercialising Nasacthin. Before approval to use the Nasacthin test in clinical practice further clinical studies are required. Data are required on the response to Nasacthin in healthy children of different ages and sex to enable doctors to define what cortisol threshold constitutes a 'pass' or a 'fail' on the new test.

Currently the diagnostic thresholds for the SST are derived from adult data and this project will establish the first normal ranges in children. This is important for doctors to have confidence in the new test and will facilitate adoption into clinical practice. Diurnal is ideally placed to help Dr Elder as a leading international endocrinology company focused on developing therapies for AI with experienced clinical, regulatory and commercial teams.

Dr Elder's secondment to Diurnal will allow progression of her career, boosting her skills in drug development. It will bring a new product to market, to benefit the UK economy, and make a major contribution to the reduction in disease burden and risk of death of children using inhaled and other steroids.