Posted on Wednesday, 17/Oct/2018 Posted by michelle

Data from European Chronocort® Phase III safety extension study shows sustained benefits of treatment over at least 12 months

Company believes total Chronocort® development package warrants Scientific Advice meeting with EMA, with view to potentially submitting MAA in Q4 2019

US Chronocort® development plans put on hold

Seeking end-of-Phase III meeting with FDA for Alkindi® ahead of a potential NDA submission in Q3 2019

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, today provides an update on its late-stage pipeline products for the replacement of cortisol deficiency, Alkindi® (hydrocortisone granules in capsules for opening) and Chronocort® (modified release hydrocortisone).

Following the Company’s announcement on 8 October 2018 that Chronocort® had not met the primary endpoint in its European Phase III trial for the treatment of congenital adrenal hyperplasia (CAH), Diurnal has undertaken further analysis of the clinical trial data, identifying important differences between Chronocort® and the control arm of the trial. Diurnal has also analysed interim data from the ongoing safety extension study in Europe, an open-label, ‘roll-over’ trial in which patients from the Phase III trial have continued Chronocort® treatment. Notably, a number of patients on the safety extension trial have now been treated for at least 12 months and show sustained benefit from extended Chronocort® treatment, consistent with feedback from the study investigators in this open-label trial. Based on the further analyses of data from these largest ever treatment studies in CAH, Diurnal intends to request a Scientific Advice meeting with European regulators before the end of the 2018, with a view to submitting a Marketing Authorisation Application (MAA) for Chronocort® in Q4 2019, including application for Orphan Drug Designation in the treatment of CAH.

While the comprehensive dataset from the European trials is analysed, and until the implications for CAH care are understood, Diurnal has put on hold all activities relating to the US development of Chronocort®.

Separately, for Alkindi®, Diurnal has now completed a development programme for a US New Drug Application (NDA) submission, including a study to demonstrate bioequivalence with the US reference product. The Company will now proceed to an end-of-Phase III meeting with the US Food and Drug Administration (FDA) at the earliest opportunity to seek agreement that the package of data is suitable for an NDA submission, planned for Q3 2019.

Martin Whitaker, Chief Executive Officer of Diurnal, commented:
“We remain positive that Chronocort® will provide a valuable treatment option for patients with CAH and look forward to discussing our extensive data set with regulators. In light of our observations regarding the European Phase III trial data, and the requirement to manage our costs carefully, we have taken the decision to put all Chronocort® US development activity on hold, and to adjust our cost base accordingly.

We continue to be pleased with the progress of the commercial roll-out of our lead product, Alkindi®, across Europe following its launch in May 2018. We expect by early 2019 that Alkindi® will be commercially available in the UK, Germany, Austria and the Nordic region. We also remain focused on completing pricing negotiations in key European territories as well as the finalisation of the clinical data package for Alkindi® in the US for submission to the FDA.”

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014 (MAR).

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

Diurnal Group plc +44 (0)20 3727 1000
Martin Whitaker, Chief Executive Officer 
Richard Bungay, Chief Financial Officer 

Panmure Gordon (UK) Limited (Nominated Adviser and Joint Broker) +44 (0) 20 7886 2500
Corporate Finance: Freddy Crossley, Emma Earl
Corporate Broking: James Stearns

Cantor Fitzgerald Europe (Joint Broker) +44 (0) 20 7894 7000
Corporate Finance: Phil Davies, Will Goode, Michael Boot
Healthcare Equity Sales: Andrew Keith

FTI Consulting +44 (0)20 3727 1000
Simon Conway 
Victoria Foster Mitchell

Notes to Editors

About Chronocort®
Chronocort® is a modified release preparation of hydrocortisone that has been designed to mimic the circadian rhythm of cortisol when given in a twice-a-day “toothbrush” regimen (last thing at night before sleep and first thing in the morning on waking) to control androgen excess and chronic fatigue in patients with diseases of cortisol deficiency. The first planned indication for Chronocort® is Congenital Adrenal Hyperplasia (CAH) in adults. Chronocort® has been extensively studied in humans having completed four Phase I trials, a Phase II trial in 16 CAH patients in the US in 2014, and a Phase III trial in 122 CAH patients in Europe.

In Europe, Chronocort® has been granted Orphan Drug Designation in the treatment of CAH, which, if confirmed at marketing authorisation, provides market exclusivity for 10 years. The market authorisation of Chronocort® in Europe is anticipated in 2020.

About Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) is an orphan condition caused by deficiency of adrenal enzymes, most commonly 21-hydroxylase. This enzyme is required to produce the adrenal steroid hormone, cortisol. The block in the cortisol production pathway causes the over-production of male steroid hormones (androgens), which are precursors to cortisol. The condition is congenital (inherited at birth) and affects both sexes. The cortisol deficiency and over-production of male sex hormones can lead to increased mortality, infertility and severe development defects including ambiguous genitalia, premature (precocious) sexual development and short stature. Sufferers, even if treated, remain at risk of death through an adrenal crisis.

Current therapy for CAH uses a variety of generic steroids (hydrocortisone, dexamethasone and prednisolone). Approximately two-thirds of CAH patients are estimated to have poor disease control, leading to elevated androgen levels. The condition is estimated to affect a total of approximately 47,000 patients in Europe, with over 400,000 in the rest of the world.

About Alkindi® (hydrocortisone granules in capsules for opening)
Alkindi® is the first preparation of hydrocortisone specifically designed for use in children suffering from paediatric Adrenal Insufficiency (AI). Alkindi® is a patented, oral, immediate-release paediatric formulation of hydrocortisone granules in capsules for opening that allows for accurate age-appropriate dosing in children. This therapeutic approach has the potential to help young patients less than eighteen years of age suffering from diseases due to cortisol deficiency including paediatric AI and CAH. AI requires life-long treatment and Diurnal’s novel approach to product development has the potential to significantly improve these young patients’ lives. On 9 February 2018, the European Commission granted a paediatric use marketing authorisation (PUMA) for Alkindi® as replacement therapy of AI in infants, children and adolescents (from birth to <18 years old), following the positive opinion issued by the European Medicines Agency in December 2017. The PUMA affords 10 years’ market and data exclusivity for Alkindi® in Europe.

About Paediatric Adrenal Insufficiency
Paediatric AI, including the genetic condition CAH is a condition characterised by deficiency in cortisol, an essential hormone in regulating metabolism and the response to stress. The primary symptoms of paediatric AI are precocious puberty, chronic fatigue with the additional risk of adrenal crisis and death if they do not have adequate cortisol replacement. Paediatric AI is either primary or secondary, with primary AI resulting from diseases intrinsic to the adrenal gland and secondary AI resulting from pituitary diseases where there is a failure of stimulation of the adrenal by the pituitary of the signalling hormone ACTH (adrenocorticotropic hormone). In Europe, paediatric AI has been identified as a rare condition, where there are estimated to be approximately 4,000 sufferers younger than the age of six, where the need for an effective replacement therapy is greatest. Prior to the European approval of Diurnal’s product, Alkindi®, paediatric AI was treated by compounding hydrocortisone or crushing/splitting tablets of hydrocortisone (the synthetic version of cortisol) as there was no licensed formulation available specifically designed for children.

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.

For further information about Diurnal, please visit www.diurnal.co.uk

Date of Preparation: Oct 2018                Code: CH EU-EU-0052