LONDON – Endocrine specialist Diurnal Group plc turned in positive phase III results in the pivotal study of Infacort, clearing the way for the first licensed pediatric formulation of hydrocortisone for treating adrenal insufficiency to reach the market in 2017.

Currently, children with adrenal insufficiency are treated with compounded adult tablets or other unlicensed products. Infacort is a patented, immediate-release formulation that for the first time will allow for precise age-appropriate dosing, meaning treatment can be tailored to children as they grow. The phase III trial included a cohort of neonates, ages 0 to 6 months.

"We are extremely pleased to achieve these results and to be close to getting our first product to patients," said Martin Whitaker, Diurnal CEO. "We are now on target to file with the EMA later this year," he told BioWorld Today.

In the phase III open-label study involving 24 children, from 0 to 6 years, Infacort met the primary endpoint, demonstrating a statistically significant (p<0.0001) increase in cortisol levels after a single dose of the artificial hormone. There were no safety concerns.

Cardiff, U.K.-based Diurnal is now planning a U.S. trial of Infacort, and following feedback from the FDA, will commence a phase III study later in 2016. Whitaker said the European data are not adequate because in the U.S. there is no product licensed for children ages 0 to 16 years. "The FDA wants another trial including children up to 16, which we are now finalizing with them," he said.

According to Whitaker, the lack of an appropriate pediatric formulation means children are not being treated satisfactorily. Poor control of cortisol levels can result in precocious puberty in young children, virilization in girls and chronic fatigue.

Development of Infacort was supported by a $6.1 million grant from the EU, which included funding for manufacturing scale-up and the clinical program.

The product has EMA pediatric use marketing authorization, a route that provides 10 years of data exclusivity.

Adrenal insufficiency, caused by congenital adrenal hyperplasia, primary adrenal failure or hypopituitarism, is classified as a rare disease. In Europe, there are estimated to be approximately 4,000 patients under the age of 6.

In some countries, including Germany where the phase III took place, there is a neonatal screening program. However, Whitaker said, in the absence of routine screening, pediatric endocrinologists "are good at picking up the symptoms."

Following close behind Infacort, Diurnal's second program, Chronocort, is in a phase III trial for treating adults with adrenal insufficiency. The product is formulated to have the same release profile as endogenous cortisol, production of which increases overnight to reach a peak in the early morning.

Chronocort mimics that circadian rhythm by using a microparticulate formulation that results in sustained release and by "toothbrush" dosing in which a higher dose is taken at bedtime and a lower dose in the morning.

The phase II development of Chronocort was carried out under a U.S. NIH cooperative R&D agreement.

The phase III European study, which began in February 2016, will include 110 patients who currently are being treated with steroids. Each will receive Chronocort for six months. "The Chronocort program is going to plan. The pivotal phase III is underway and recruitment is ongoing with results due in the first quarter of 2018," Whitaker said.

One of the objectives of the EU-funded Infacort program was to lay the foundation for a long-lasting collaboration among industry, clinicians and patients. As a result of that, and of the NIH backing, Diurnal has built relationships with leading endocrinologists on both sides of the Atlantic. Those relationships will underpin the commercialization strategy, with Diurnal planning to go it alone in marketing the products.

As Whitaker noted, patients with adrenal insufficiency need life-long daily hormone replacement therapy. "The combination of Infacort and Chronocort will allow us to build a valuable franchise to treat a rare disease from birth through to old age."