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.
Diurnal CEO Martin Whitaker said: “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.”