DNL.L Regulatory News (DNL)

02 February 2021

Diurnal Group plc

("Diurnal" or the "Company")

Chronocort® Phase 3 and Safety Extension Study results published in JCEM

Peer-reviewed data from largest ever completed interventional clinical trial in CAH

Authors conclude that Chronocort® provides a well-tolerated and practical twice-daily treatment regimen for CAH

Data also forms part of EMA and MHRA submissions with anticipated positive regulatory opinion in Q1 2021

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces that the endocrinologist-focused Journal of Clinical Endocrinology and Metabolism ("JCEM") has today published the peer-reviewed results of the Company's Phase 3 clinical trial and extension study for Chronocort® (hydrocortisone modified-release hard capsules) in patients with the rare condition congenital adrenal hyperplasia (CAH).

The Company's Phase 3 study was conducted in a total of 122 patients enrolled across 11 clinical sites, the largest ever interventional clinical trial completed in CAH patients. Data are also presented from an open-label safety extension study for patients completing treatment in the Phase 3 study. These data assessed the impact of treatment with Chronocort® over a further period of 18 months. A significant proportion of patients eligible to enter the follow-on study did so, and patient retention rates in this study remain high.

As previously announced, the Phase 3 study results published by the JCEM found that although the standard-deviation-score-focused primary endpoint of the study was missed, Chronocort® improved morning and early afternoon biochemical control for adults with CAH over standard glucocorticoid therapy. In the safety extension study, biochemical control was sustained for 18 months on median hydrocortisone doses in the range recommended for cortisol replacement therapy and lower than glucocorticoid doses normally used in the treatment of CAH. The manuscript concludes that Chronocort® provides a well-tolerated and practical twice-daily treatment regimen for CAH in adults, due to a deficiency of 21-hydroxylase.

The JCEM advanced article, entitled "Modified-release Hydrocortisone in Congenital Adrenal Hyperplasia" can be accessed here: https://academic.oup.com/jcem/article-lookup/doi/10.1210/clinem/dgab051

Chronocort® is a modified-release preparation of hydrocortisone that is under review by the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), with the submissions based on the Phase 3 clinical trial and safety extension study data. If regulatory review is successful, marketing authorisation opinions for Chronocort® approval in the European Economic Area (including Northern Ireland) and Great Britain are anticipated during Q1 2021.

Data from the JCEM manuscript, the Chronocort® Phase 3 clinical trial and extension study will be included in the Company's analyst presentation, on Tuesday 23 February 2021 for the financial results for the six months ended 31 December 2020, which will be available on the Company's website shortly thereafter.

Professor Richard Ross, a founding Director of Diurnal and Chief Scientific Officer, commented:

"The team at Diurnal and I are delighted to have our data from the Chronocort® Phase 3 clinical trial and safety extension study published in the prestigious Journal of Clinical Endocrinology and Metabolism. These results confirm the effectiveness of Chronocort®, which provides a much needed, well-tolerated and practical twice-daily treatment regimen for adults with CAH due to a deficiency of 21-hydroxylase."

Martin Whitaker, Chief Executive Officer of Diurnal, commented: 

"Today's peer-reviewed publication in the JCEM is a significant milestone and discloses the full data set behind our European pivotal clinical study for Chronocort® as a potential treatment for CAH. This data has also formed part of our submissions to the EMA and MHRA, where we anticipate positive regulatory opinion during this quarter. If approved, Chronocort® could be a valuable treatment option for CAH patients across Europe, a rare condition that we estimate affects a total of approximately 41,000 people."

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

Notes to Editors

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 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 a total of approximately 41,000 patients in Europe, with over 400,000 in the rest of the world.

About Chronocort®

Chronocort® is a modified-release preparation of hydrocortisone that has been specifically 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 and adolescents. Chronocort® has been extensively studied in human subjects 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 and the US.

About Diurnal Group plc

Founded in 2004, Diurnal is a UK-headquartered, European specialty pharma company developing hormone therapeutics for the global market for the life-long treatment of chronic endocrine conditions, including congenital adrenal hyperplasia, adrenal insufficiency and hypogonadism. 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: February 2021 Code: CORP-GB-0100