DNL.L Regulatory News (DNL)

12 February 2018

Diurnal Group plc

("Diurnal" or the "Company")

Completion of patient enrolment in European pivotal Phase III clinical study of Chronocort® for the treatment of Congenital Adrenal Hyperplasia

Study scheduled to complete in Q3 2018; potential market authorisation in Europe in 2020

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces that it has successfully completed patient enrolment for its European pivotal Phase III clinical trial of Chronocort® (modified release hydrocortisone) for the treatment of Congenital Adrenal Hyperplasia (CAH) in adults.

The Phase III trial is an open label study in which adult patients with CAH, currently treated with a single or combination of generic steroids (standard-of-care), are randomised to either receive Chronocort® on a twice daily "toothbrush" regimen or continue on their standard-of-care regimen. The primary endpoint of the trial is the control of androgens (sex hormones) at six months on equivalent or lower total daily dose of steroid when treated with Chronocort® compared to standard-of-care treatment. This primary endpoint is similar to an endpoint previously reported in the Phase II clinical trial, where the data showed a significant reduction in the morning levels of 17-hydroxyprogesterone (the main androgen) in patients after six months on Chronocort® (median 70nmol/l vs 5.65nmol/l p= 0.014), with 94% of values in the normal or optimal range compared to 31% before Chronocort® therapy[i]. Secondary endpoints will include an assessment of fatigue levels and the relative effect of Chronocort® on body mass index and bone turnover, all of which are indicative of clinical benefits. Headline data from this trial is expected in Q3 2018 and, if positive, could lead to potential market authorisation in Europe in 2020.

CAH is an orphan condition usually caused by deficiency of the enzyme 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 has been associated with increased mortality, infertility, reduced quality of life and cardiovascular morbidity. Sufferers, even if treated, remain at risk of death through an adrenal crisis.

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 64,000 patients in Europe (47,000) and the US (17,000), with over 400,000 in the rest of the world. Current therapy for CAH uses a variety of generic steroids (hydrocortisone, dexamethasone and prednisolone) which, at best, adequately treat approximately one-third of CAH patients. Other therapies being developed are at an early stage of development and not expected to receive approval in the short-term.

Chronocort® has been granted Orphan Drug Designations in Europe and the US in the treatment of CAH, which, if confirmed at marketing authorisation, provides market exclusivity for 10 years in Europe and seven years in the US post market authorisation.

Martin Whitaker, Chief Executive Officer of Diurnal, commented: 

"Chronocort® provides a drug release profile that has been designed to mimic the body's natural cortisol circadian rhythm more closely and therefore has the potential to achieve better CAH disease control for patients than current treatment options. As the majority of CAH patients have poor disease control, we believe Chronocort® offers the potential to significantly improve many of the symptoms of this debilitating condition. We look forward to reporting headline data from this trial in 2018."

About Chronocort®

Chronocort® is a modified release preparation of hydrocortisone (the synthetic form of cortisol) 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). The first planned indication for Chronocort® is CAH. Chronocort® has completed three Phase I trials in 2011, 2012 and 2015 and a Phase II trial in CAH patients in 2014.

Chronocort® Phase II trial

Data from the Chronocort® Phase II trial demonstrated that the trial met its primary endpoint of fully characterising the pharmacokinetic profile of Chronocort® in 16 male and female adult subjects with CAH. The results showed Chronocort® provides circadian levels of the stress hormone, cortisol, similar to the healthy population mimicking the overnight rise in cortisol levels, such that patients wake with a normal cortisol level.

In addition, the secondary objective of examining the effect of Chronocort® on the morning biochemical efficacy markers of the disease showed a significant reduction in the morning levels of 17-hydroxyprogesterone (the main androgen) in patients after six months on Chronocort (median 70nmol/l vs 5.65nmol/l p= 0.014) with 94% of values in the normal or optimal range compared to 31% before Chronocort therapyi. Chronocort® was well-tolerated during the six-month trial. The trial was reported in the Journal of Clinical Endocrinology and Metabolism (Mallappa et al JCEM 2014).

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