Diurnal receives Special Protocol Assessment Agreement for Chronocort® from the FDA


12th July 2021

Pivotal Phase 3 trial expected to commence in the US in H2 2021

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, today announces that the US Food and Drug Administration (FDA) has agreed a Special Protocol Assessment (SPA) for Chronocort® (modified-release hydrocortisone) for the design, endpoints and statistical analysis approach of a pivotal study of Chronocort® for the treatment for Congenital Adrenal Hyperplasia (CAH) in the US. The SPA provides agreement that the Phase 3 trial design adequately addresses objectives that would support the regulatory submission for drug approval.

The pivotal study is entitled “A randomised, double-blind, active-controlled, Phase 3 study of Chronocort® compared with immediate-release hydrocortisone replacement therapy in participants aged 16-years and over with Congenital Adrenal Hyperplasia (CAH)” – CONnECT – and is anticipated to start during H2 2021. Study start-up activities have already been commenced by the Company to enable a timely initiation and recruitment of up to 150 subjects with CAH who will be treated for a period of 52 weeks.

Chronocort® is a preparation of hydrocortisone that has been specifically designed for patients with CAH, an orphan condition, caused by deficiency of adrenal enzymes, most commonly 21-hydroxylase. Diurnal holds the relevant Orphan Drug Designation for use of Chronocort® in CAH in the US. 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 16,000 patients in the US.

Martin Whitaker, Chief Executive Officer of Diurnal, commented:

“We are pleased to have concluded a series of positive discussions with the FDA around the design of our pivotal Chronocort® study to support a regulatory submission for marketing approval in the US. During the first half of 2021 the Diurnal team has been working hard to complete the required preparation activities for this trial and we look forward to starting this study as soon as possible.”

This is a business press release containing financial information and/or data for the benefit of shareholders and potential investors. Data are included to allow informed investment decisions.

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 Sole Broker) +44 (0)20 7886 2500

Corporate Finance: Freddy Crossley, Emma Earl

Corporate Broking: Rupert Dearden

FTI Consulting (Media and Investor Relations) +44 (0)20 3727 1000

Simon Conway

Victoria Foster Mitchell

Alex Davis

Notes to Editors

About the FDA’s Special Protocol Assistance

The SPA process documents the FDA’s official evaluation and written guidance on the design and size of proposed protocols and agreement that the design and planned analysis of a study can adequately address objectives in support of a regulatory submission. Final determinations for marketing application approval, however, are made after a complete review of a marketing application and are based on the entire data in the application. The agreed SPA may only be changed through a written agreement between the sponsor and the FDA, or if the FDA becomes aware of a substantial scientific issue essential to product efficacy or safety.

About Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a rare 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 issues during sexual development 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 glucocorticoid (steroids including hydrocortisone, dexamethasone, prednisolone and prednisone in the US) with no standard treatment regimen. 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 16,000 patients in the US, with over 400,000 in the rest of the world.

About Chronocort® (modified-release hydrocortisone)

Chronocort® is a preparation of hydrocortisone that has been specifically designed to mimic the circadian rhythm of cortisol when given in a twice-a-day "toothbrush" regimen (administered 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 ® in the US is Congenital Adrenal Hyperplasia (CAH) in adults and children older than 16 years of age. Chronocort ® has been extensively studied in 239 human subjects including 138 CAH patients who have taken part in clinical trials in Europe and the US.

Although Chronocort® is still an investigational product in the US, Chronocort® (known in Europe as Efmody®) has already achieved marketing authorisation approval from the European Commission (in the European Economic Area) and the Medicines and Healthcare products Regulatory Agency (in Great Britain). These marketing authorisations for Efmody® are based on a Phase 3 study conducted in a total of 122 patients enrolled across 11 clinical sites, including a site in the US, the largest ever interventional clinical trial completed in CAH. The Phase 3 data was supported by detailed analysis of data from an open-label safety extension study for patients completing treatment in the Phase 3 study, which is assessing the impact of treatment with Efmody® over an extended period, with a number of patients on this trial having been treated for over 54 months. Patient retention rates in this study have been high and patients on this trial have, to date, shown sustained benefit from extended Efmody® treatment. The human medicine European public assessment report (EPAR) for Efmody® can be viewed here and the Summary of Product Characteristics (SmPC) here

About Diurnal Group plc

Diurnal Group plc is a European, UK-headquartered, specialty pharmaceutical company dedicated to developing hormone therapeutics to aid lifelong treatment for rare and chronic endocrine conditions, including congenital adrenal hyperplasia, adrenal insufficiency, hypogonadism and hypothyroidism. 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: July 2021               Code: CORP-GB-0141

Diurnal Group plc (Company Number: 09846650) is registered in England & Wales. Registered office: Cardiff Medicentre, Heath Park, Cardiff CF14 4UJ, UK.