Diurnal reports positive headline data from European Infacort® Phase III pivotal study

Primary endpoint met, with Infacort® treatment achieving target cortisol levels in children aged less than six years

Major breakthrough in paediatric Adrenal Insufficiency, a condition of high unmet medical need with no currently licensed formulation for young children

European market authorisation anticipated in late 2017

Infacort® is the first Diurnal product candidate to complete a registration study, a major milestone towards building a proprietary endocrinology franchise

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces, ahead of schedule, positive headline data from the pivotal study for Infacort® in Europe for paediatric Adrenal Insufficiency (AI).

AI is characterised by deficiency in cortisol, an essential hormone in regulating metabolism and the response to stress. It is identified as a rare disease in Europe where there are estimated to be approximately 4,000 sufferers younger than the age of six. Untreated, the disease is associated with significant morbidity. Currently there are no licensed hydrocortisone (the synthetic version of cortisol) preparations in Europe specifically designed to treat these young patients. Infacort® is on target to be the first pharmaceutically defined dose and consistent formulation of hydrocortisone designed specifically for children.

The Phase III trial was designed in agreement with the European Medicines Agency (EMA) and conducted in a total of 24 subjects before their sixth birthday, requiring replacement therapy for AI due to Congenital Adrenal Hyperplasia (CAH), primary adrenal failure or hypopituitarism.

Initial analysis of the results confirms that the study met its primary endpoint, demonstrating a statistically significant (p<0.0001) increase in cortisol values following administration of Infacort® compared to the pre-dose values. No serious adverse events were reported. A full evaluation of the data is underway and the results of this comprehensive analysis are expected later this quarter.

The EMA has already approved a Paediatric Investigation Plan (PIP) for Infacort®, setting out the regulatory pathway to market authorisation via the Paediatric Use Marketing Authorisation (PUMA) route. Diurnal is on track to submit this regulatory dossier to the EMA around the end of 2016. If approved, Infacort® has the potential to be the first licensed treatment in Europe for AI (including CAH) specifically designed for use in children. Diurnal anticipates market authorisation in late 2017.

Martin Whitaker, CEO of Diurnal, commented:

“We are pleased to announce the completion of treatment in this pivotal study and look forward to the announcement of the full clinical data package shortly. The initial results of this pivotal study are very exciting as Infacort® has the potential to address a significant unmet need for children with Adrenal Insufficiency who are not being treated satisfactorily. This marks a significant developmental milestone for Diurnal as we move towards building a proprietary endocrinology franchise based on Infacort® and our second product, Chronocort®, which is in Phase III trials in Europe for adult CAH. With Infacort® now ready for regulatory filing later this year and anticipated market authorisation in late 2017, we have taken a major step towards realisation of our vision.”

Following US Food and Drug Administration (FDA) feedback, Diurnal will be commencing the US registration programme for Infacort® in 2016.

Infacort® is Diurnal’s most clinically advanced product and is the first preparation of hydrocortisone specifically designed for use in children suffering from AI. The patented, immediate-release oral product has been designed to meet the dosing needs of children for whom no child-appropriate licensed products exist in Europe or in the US. Infacort® is manufactured using commercially proven technology in paediatric acceptable doses in order to give maximum flexibility to clinicians in tailoring treatment to children as they develop and grow. Currently, pharmacists often compound (grind) hydrocortisone tablets to a fine powder and reconstitute it in individual capsules or sachets to achieve the lower doses required for children. Compounding can be highly variable and may result in inaccurate dosing to patients.

It is Diurnal’s ambition to develop an adrenal product franchise that can treat patients with all forms of cortisol deficiency, including AI and CAH, with the Company’s second product, Chronocort®, currently in Phase III clinical development in Europe for adults with CAH. The Chronocort® trial is scheduled to complete by Q1 2018. This implies a potential market authorisation in Europe could be forthcoming around year end 2018.

Overview of Infacort® pivotal trial design

The pivotal phase III trial was an open-label study of Infacort® in neonates and children up to <6 years of age with adrenal insufficiency carried out at Charité-Universitätsmedizin, Berlin Germany and consisted of three cohorts that were carried out in series:

-       Cohort 1: 12 patients with adrenal insufficiency aged 2 – 6 years of age

-       Cohort 2: 6 patients with adrenal insufficiency aged 1 month to 2 years of age (infants)

-       Cohort 3: 6 patients with adrenal insufficiency aged 0 to 1 month of age (neonates)

For further information, please visit www.diurnal.co.uk  or contact:

Diurnal Group PLC  

+44 (0)20 3727 1000 

Martin Whitaker, CEO 

Ian Ardill, CFO

Numis Securities Ltd 

+44 (0)20 7260 1000 

Nominated Adviser: Michael Meade, Freddie Barnfield, Paul Gillam 

Corporate Broking: James Black

FTI Consulting 

+44 (0)20 3737 1000 

Simon Conway 

Victoria Foster Mitchell

About Adrenal Insufficiency

Adrenal Insufficiency (AI) is a condition characterised by deficiency in cortisol, an essential hormone in regulating metabolism and the response to stress.  AI has been identified as a rare disease in Europe where there are estimated to be approximately 4,000 sufferers younger than the age of six.  Currently there are no licensed hydrocortisone preparations in Europe specifically designed to treat these young patients.  These children are often administered compounded adult tablets or other unlicensed products.  Poor control of disease can result in precocious puberty in young children, virilisation in girls and chronic fatigue leading to a poor quality of life in adulthood resulting in increased morbidity and mortality.

About Infacort®

Infacort® represents the first preparation of hydrocortisone specifically designed for use in children suffering from AI.  It is a patented, immediate-release, oral, paediatric formulation of hydrocortisone that allows for age-appropriate dosing in children.  This therapeutic approach has the potential to help young patients less than six year of age suffering from diseases due to cortisol deficiency including adrenal insufficiency and congenital adrenal hyperplasia.  AI requires life-long treatment and Diurnal’s novel approach to product development has the potential to significantly improve these young patients’ lives.  The European Medicines Agency has already approved a Paediatric Investigation Plan (EMEA-001283-PIP01-12) for Infacort®, which sets out the regulatory pathway to market authorisation via the Paediatric Use Marketing Authorisation (PUMA) route.

About Diurnal Group plc

Founded in 2004, Diurnal is a UK-based specialty pharma company developing high quality products for the global market for the life-long treatment of chronic endocrine conditions, including Congenital Adrenal Hyperplasia and Adrenal Insufficiency.  Its expertise and innovative research activities focus on circadian-based endocrinology to yield novel product candidates in the rare and chronic endocrine disease arena.

The primary objective of the study was to measure peak and four-hour cortisol levels after administration of a single dose of Infacort®. The secondary objective was safety.