Posted on Friday, 05/Oct/2018 Posted by michelle

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces that the first two patients have been enrolled into the Chronocort® (modified release hydrocortisone) pivotal Phase III clinical trial (“RESTORE”) in the US for adults with congenital adrenal hyperplasia (CAH).

The RESTORE study will recruit up to 150 patients, who will be randomised to either receive Chronocort® twice-daily or their current standard of care. Patients in the study will be treated for 52 weeks, with the primary endpoint of the study being the proportion of patients achieving biochemical control with Chronocort® or standard of care. The study will also assess the impact of treatment on a number of important clinical outcomes. RESTORE is the pivotal Phase III clinical trial designed to study treatment interventions in adults with CAH in the US and is expected to be completed in late 2020, with an NDA filing in the US planned for 2021.

CAH is an orphan condition caused by a block in cortisol production, an essential adrenal steroid hormone required for healthy life. A lack of cortisol in turn causes the over-production of male steroid hormones (androgens). Cortisol deficiency and over-production of androgens can lead to increased mortality, infertility and severe development defects, including ambiguous genitalia, precocious puberty and short stature. Sufferers, even if treated, remain at risk of death through an adrenal crisis.

The US is a core market for Chronocort® with an estimated market size for the treatment of CAH alone of $110 million and the market size for the treatment of the related condition, adrenal insufficiency (AI) estimated at $880 million. Diurnal expects to initiate a Phase II study in US centres for Chronocort® in AI patients around the end of 2018. Chronocort® has been granted Orphan Drug Designations in the US in the treatment of CAH and AI, providing the potential to be granted market exclusivity for seven years in the US post market authorisation, in addition to the Company’s granted patients which provide protection until 2033.

Martin Whitaker, Chief Executive Officer of Diurnal, commented:
“We are pleased to have enrolled the first patients in this pivotal study for congenital adrenal hyperplasia. The majority of patients with this condition are not being adequately treated with current therapy, leading to poor disease control. We believe Chronocort® is able to address this unmet need by providing a drug release profile in line with the body’s natural cortisol circadian rhythm. The US represents an important opportunity for Chronocort® to improve the lives of patients with diseases of cortisol deficiency whose needs are currently not being met by treatments available.”

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 RESTORE
The RESTORE study is an open-label, Randomised, titration-blinded, parallel arm, multi-centre, Phase III study of Efficacy, Safety and Tolerability Of Chronocort® compared with standard glucocorticoid REplacement therapy in the treatment of participants aged 16 years and over with CAH.

This study will be conducted in the US by Worldwide Clinical Trials, Diurnal’s preferred CRO partner, and will compare the efficacy, safety and tolerability of twice daily Chronocort® with standard of care (using the participant's usual individualised standard glucocorticoid regimen) over a treatment period of 52 weeks.

The primary endpoint of the study is the proportion of participants after 52 weeks of treatment in the Chronocort® and standard of care treatment groups achieving biochemical control. The study design is similar to the European Phase III study in CAH, which has a primary endpoint of the proportion of patients achieving biochemical control with Chronocort® or standard of care after 26 weeks of treatment. The RESTORE study will also assess the impact of both treatments on clinically relevant secondary endpoints including:  markers of fertility, hirsutism in female participants, treatments on acne, glycated haemoglobin (HbA1c) levels, body composition, body weight and on quality of life using a number of validated assessments.

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 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 the treatment phase for the European Phase III trial in 122 CAH patients. This pivotal Phase III trial for Chronocort® in Europe is scheduled to read out headline results in early Q4 2018, with market authorisation in Europe 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 approximately 17,000 patients in the US, with over 400,000 in the rest of the world.

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: October 2018  Code:CH US-GB-0004