Researchers develop first cortisol treatment specifically designed for infants
EU-funded researchers have developed a treatment tailored for babies and children lacking the stress hormone cortisol. The drug, the first hydrocortisone formulation specifically designed for infants, could become available next year following successful clinical trials.
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Around one in 12 000 children are born with congenital adrenal hyperplasia (CAH), a genetic mutation that blocks production of cortisol by the adrenal gland. Known as the stress hormone, cortisol has a critical role in combating infections and other sources of physical stress such as extreme exercise or surgery: without it infants cannot survive.
The TAIN project has developed a cortisol replacement therapy to treat CAH and other adrenal insufficiency disorders based on a new preparation of the steroid hydrocortisone, the synthetic version of cortisol, designed specifically for children from birth up to six years. Developed under the name Infacort, the product is currently being evaluated by the European Medicines Agency (EMA) following successful phase III clinical trials by the project consortium.
If approved by the EMA, Infacort will constitute a major step forward in the treatment of children with adrenal insufficiency, says Martin Whitaker, TAIN coordinator at the University of Sheffield in the UK, and CEO of pharmaceutical firm Diurnal. It will also support the EMAs efforts to promote the development of drugs specifically formulated for newborn babies and young children, rather than relying on treatments intended for adults.
Currently, children with adrenal insufficiency are treated with unlicensed preparations derived from adult hydrocortisone drugs. These are usually prepared by pharmacists by dividing adult hydrocortisone tablets or crushing them and mixing them in a sweetened liquid to make them more palatable to infants.
Although this approach has saved the lives of thousands of children, it carries considerable risks of under- or over-treatment due to incorrect dosage which can result in long-term health problems, including development and growth disorders, obesity, osteoporosis and premature death.
Infacort is set to be the first licensed preparation of hydrocortisone specifically adapted for paediatric use, with dose strengths suitable for babies and young children. It addresses the above risks by ensuring the correct dosage based on body weight, and including features such as ease of administration and taste-masking to make it palatable to babies and children, Whitaker says.
Because of the very young patient group, the consortium developed Infacort using computation models to evaluate drug behaviour that enabled the researchers to minimise patient testing. The work drew on the extensive neonatology, paediatric pharmacology and clinical trial methodology expertise of the consortium members, including Professor Richard Ross, a founder of Diurnal, from the University of Sheffield's Medical School, a leading international centre of research into rare neonatal diseases.
Safe and effective therapy for adrenal insufficiency
Subsequent clinical studies, conducted following approval of a Paediatric Investigation Plan by the EMA, showed the formulations efficacy and safety.
In the phase III trials, conducted at Charité - Universitätsmedizin Berlin, Infacort was administered to three groups of patients aged two to six years, one month to two years, and from birth to one month old.
The results confirmed that Infacort resulted in a statistically significant increase in cortisol levels compared to pre-dose values, with the median cortisol level achieved 60 minutes after treatment comparable to the mean peak morning cortisol in healthy children, with no adverse effects reported.
Surveys showed that 82 % of parents and caregivers found it easy to administer Infacort, 95 % would be happy to give their child Infacort, and 95 % preferred it to the usual, unlicensed hydrocortisone preparations rising to 100 % of respondents among parents of children aged zero to 28 days.
These important data suggest that Infacort could be an effective and safe cortisol replacement treatment able to address a significant unmet need for children with adrenal insufficiency. Infacort also has the potential to increase compliance through the products taste-masking excipients specifically designed to eliminate the bitter taste of hydrocortisone, says Dr Oliver Blankenstein, a co-investigator on the trials.
If approved by the EMA, Diurnal, a pharmaceutical SME spun out of the University of Sheffield, plans to start commercialising Infacort possibly this year, marking an important advance in treating infant adrenal insufficiency and, more broadly, in efforts to develop drugs specifically for babies and children.
Due to numerous ethical and practical challenges of testing medications, newborns and infants have been at a disadvantage regarding new medical treatment because they have had to be treated with drugs developed for adults. According to Whitaker, the TAIN project demonstrates it is possible to successfully address those challenges, providing for future medical research collaborations focused on improving treatments for children.