First patient dosed in Chronocort® pivotal study

29 February 2016

Diurnal Group plc

("Diurnal" or the "Company")

First patient dosed in Chronocort® pivotal clinical study for Congenital Adrenal Hyperplasia

Two lead products in Phase III clinical development

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces that the first patient has been dosed in the Chronocort® pivotal Phase III clinical trial in Europe for adults with Congenital Adrenal Hyperplasia ("CAH").

The Phase III trial is prospectively designed to study approximately 110 patients in an open-label six month protocol. Enrolled patients currently treated with a single or combination of generic steroids ("standard of care") will be randomised to Chronocort® on a twice daily "toothbrush" regimen or will continue on their standard-of-care regimen. As previously communicated, following discussions with the European Medicines Agency ("EMA"), the primary endpoint of the trial is the control of androgens on the same or lower total daily dose of steroid when treated with Chronocort® compared to standard-of-care treatment. This primary endpoint is identical to the previous successful Phase II clinical trial for Chronocort® for which data were released in 2014. 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. As previously expected, the trial is scheduled to complete by Q1 2018. This implies a potential market authorisation in Europe could be forthcoming in Q4 2018.

CAH is an orphan condition caused by a block in cortisol production, an adrenal steroid hormone. A lack of cortisol in turn causes the over-production of male steroid hormones (androgens). Cortisol deficiency and over-production of male sex hormones 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 condition is congenital (inherited) and affects both sexes.

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 71,000 patients in Europe (51,000) and the US (20,000), with approximately 405,000 in the rest of the world.

Dr Martin Whitaker, CEO of Diurnal, commented: 

"The majority of adult patients with CAH are not being treated satisfactorily with currently available steroids, which are not able to provide a release profile in line with the body's natural cortisol circadian rhythm. We believe Chronocort® is able to address this need and therefore improve disease control for adults with CAH. We look forward to successfully completing this pivotal study and delivering Chronocort® as a significant treatment option for CAH patients, with market authorisation in Europe anticipated in late 2018."

With the start of dosing in this Chronocort® European study, both of Diurnal's lead products are now in Phase III clinical development, with Infacort® currently undergoing a pivotal study in Europe for Adrenal Insufficiency ("AI") (including CAH) in children under six years of age. The Infacort® trial is scheduled to be completed by Q3 2016.

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About Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia ("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 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.

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 71,000 patients in Europe (51,000) and the US (20,000), with approximately 405,000 in the rest of the world.

Current therapy for CAH uses a combination of generic steroids (hydrocortisone, dexamethasone and prednisolone) and, at best, these 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.

About Chronocort®

Chronocort® is a modified release hydrocortisone preparation that has been designed to mimic the natural 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). Chronocort has been granted orphan drug designations in Europe and the US in the treatment of Congenital Adrenal Hyperplasia ("CAH") and Adrenal Insufficiency ("AI"). The first planned indication for Chronocort® is CAH. Chronocort® has completed three Phase I trials in 2011, 2012 and 2015 (food effects study) and a Phase II trial in CAH patients in 2014.

Phase II

Data from the Chronocort® Phase II trial demonstrate 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 show 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 significant control in 94 per cent. of the patients having their morning levels of the androgens, 17-hydroxyprogesterone (170HP) and androstenedione (A4), brought into the optimal range after six months' treatment with titrated Chronocort®, compared to poorer control (only 31 per cent. controlled) on standard treatment at the beginning of the study. Chronocort® was well-tolerated during the six month trial.

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 ("CAH") and Adrenal Insufficiency ("AI"). Its expertise and innovative research activities focus on circadian-based endocrinology to yield novel product candidates in the rare and chronic endocrine disease arena.