Diurnal Limited , a spin-out company from the University of Sheffield, today announced positive results from its Phase 2 CATCH (Chronocort® As Treatment for Congenital Adrenal Hyperplasia) clinical study in 16 adults with the rare disease Congenital Adrenal Hyperplasia (CAH).
The trial successfully met its primary objective of fully characterising the pharmacokinetic profile of Chronocort® in adult subjects with Congenital Adrenal Hyperplasia. The 24-hr Chronocort® pharmacokinetics in patients were comparable to those in the Phase 1 clinical trial of dexamethasone suppressed healthy adult volunteers. 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 biochemical efficacy markers of the disease showed significant control of the 24-hr levels of the androgens, 17-hydroxyprogesterone (170HP) and androstenedione (A4) which were brought into their optimal ranges after 6 months treatment with titrated Chronocort® compared to standard treatment.
Chronocort® was safe and well tolerated during the 6 month trial.
The results of the CATCH trial were presented at the US ENDO Conference on 21st June 2014 by the National Institute on Health (Bethesda, US) where the trial was run under a Cooperative Research and Development Agreement (CRADA).
About Congenital Adrenal Hyperplasia
Congenital Adrenal Hyperplasia is a condition characterised by deficiency in the stress hormone cortisol due to an inherited enzyme defect in the adrenal gland. Cortisol is an essential hormone in regulating metabolism and the response to stress. Cortisol levels are controlled by the central brain clock and build over night from 3am to peak in the morning and fall to low levels in the evening. In Congenital Adrenal Hyperplasia, the deficiency in cortisol results in the brain trying to stimulate the adrenal gland and a build-up in pre-cursor hormones that are androgens (testosterone like). This build up in androgens occurs from 3am in the morning and lasts through the day. The excess androgens cause precocious puberty in boys and girls, virilisation in women and infertility in men and women. Thus, patients with Congenital Adrenal Hyperplasia have two problems, a deficiency in cortisol and an excess of androgens.
CAH has been identified as an orphan disease in Europe where there are estimated to be approximately 30,000 sufferers in Europe and a further 21,000 sufferers in the US. Current therapy for CAH involves replacing cortisol with one or a combination of the synthetic steroids; cortisone, hydrocortisone, prednisolone and dexamethasone. However, these steroid formulations are unable to stimulate the cortisol rise over night and patients are either exposed to too little or too much steroid. Deficient steroid levels result in high androgens complicated by precocious puberty, virilisation and infertility combined with fatigue and a poor quality of life. Excess steroid levels result in obesity, hypertension, diabetes, and osteoporosis. Recent studies suggest that only a third of patients with Congenital Adrenal Hyperplasia have adequate control of the disease and the other two thirds are exposed to either excess or deficient steroids. There is therefore an important unmet need for a steroid therapy that replaces the circadian rhythm of cortisol and improves the control of androgens in Congenital Adrenal Hyperplasia.
Chronocort® is a patented, modified-release, oral formulation of hydrocortisone that allows for release of the hormone into the body in a manner that mimics the natural circadian (24-hr) levels of the natural hormone. This therapeutic approach has the potential to help patients suffering from diseases due to cortisol deficiency; congenital adrenal hyperplasia and adrenal insufficiency. Each of these diseases requires life-long treatment and Diurnal's novel approach to drug delivery has the potential to significantly improve patients' lives. Chronocort® already has received two related Orphan Drug designations from the European Medicines Agency, which afford ten years of market exclusivity after the grant of marketing authorisation in Europe.
Alan Aubrey, Chief Executive of IP Group, said "This is an extremely important milestone for both Diurnal and IP Group. Diurnal, which became part of the IP Group portfolio through our recent acquisition of Fusion IP, exemplifies how we are supporting our later-stage companies as they progress towards commercialisation. Having achieved this Phase 2 result, Diurnal is now on the brink of a pivotal Phase 3 study that will take Chronocort® to market."
Martin Whitaker, CEO of Diurnal, stated: 'These results, which show significantly improved control of the disease androgens, demonstrate a robust proof of concept for Chronocort® in the target patient population. Diurnal has already started Phase 3 activities as we seek to progress Chronocort® towards market authorisation. The CATCH results are a significant value point for the company and have de-risked further development activities as Diurnal seeks to develop a high quality product for diseases of cortisol deficiency including Congenital Adrenal Hyperplasia."
Melanie Goward, Deputy Fund Manager in Finance Wales' technology ventures team said "We're deighted with the positive outcome of the Chronocort® CATCH Phase 2 trial as well as the progress Diurnal is making towards launching a marketed orphan drug product with the potential to treat the rare disease, CAH. It is now well-placed to capitalise on these results and to engage with pharmaceutical and biotechnology companies searching for acquisition and partnership opportunities. Diurnal is also currently recruiting additional clinical development roles based at its Welsh headquarters to underpin its continued expansion."