MORRISVILLE, N.C.—(BUSINESS WIRE)—Worldwide Clinical Trials, Inc., (Worldwide) announced today that Diurnal (Diurnal; AIM: DNL), a specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, has appointed Worldwide as its preferred provider of clinical trial services, initially to support the US clinical development of Chronocort® in both congenital adrenal hyperplasia (CAH) and adrenal insufficiency (AI).
Diurnal selected Worldwide on the merit of the company’s experience in rare and orphan disease clinical research. Chronocort® provides a drug release profile that Diurnal believes mimics the body’s natural cortisol circadian rhythm, which current therapy is unable to replicate, and is designed to improve disease control for adults with CAH and AI.
Demand is rapidly growing for trials in rare and orphan diseases – rare is defined as a disease that affects a very small percentage of the population, while orphan diseases have no definitive, convincing treatment – due to US and EU legislation that has established incentives to support research in these areas. For example, the US remains an important market for Diurnal’s late-stage pipeline focused on cortisol deficiency, with a market size for the treatment of CAH estimated at $110 million. The AI market is a much larger opportunity, with the US market estimated at $880 million.
Worldwide’s scientific, medical, operational and regulatory experts are proficient at meeting the special demands of rare disease clinical research. Challenges include recruiting small populations across a high number of sites, complex case administration, scientific limitations, innovative study designs and biostatistical analyses accommodating small sample sizes and patient heterogeneity, and seamless communication with regulatory authorities throughout the process. The experts at Worldwide are adept at accessing small populations as well as pediatric populations, confirming and facilitating site GCP adherence, implementing innovative, efficient study designs and participatory research models, managing supportive-care endpoints, minimizing subject and caregiver burden, submitting INDs for novel or repurposed products, and leveraging strong relationships with patient advocacy groups.
Martin Whitaker, PhD, Chief Executive Officer of Diurnal, commented, “With its extensive experience in planning and recruiting studies in rare and orphan diseases, Worldwide is the ideal partner to support the US clinical development of Chronocort® for the treatment of congenital adrenal hyperplasia and adrenal insufficiency. The US represents an estimated total market opportunity of approximately $1 billion for Chronocort® in these two disorders. We are looking forward to working with Worldwide as we commence the Phase III registration package in mid-2018.”
Diurnal expects to initiate the Phase III study around the middle of 2018. The Phase III study will recruit up to 150 patients with CAH, who will be randomized to either receive Chronocort® twice daily or immediate-release hydrocortisone thrice daily. Patients in the study will be treated for 12 months, with the primary endpoint of the study being the proportion of patients achieving biochemical control with Chronocort® or standard of care.
Peter Benton, President and COO, Worldwide Clinical Trials, added, “Worldwide is thrilled to partner with Diurnal in their quest to improve the lives of those who suffer from CAH and AI. When the experts at Worldwide bring their uncommon expertise in orphan and rare disease clinical research to bear against the unique challenges these patients and populations present, sponsors gain a significant level of flexibility and insight. This combination helps increase collaboration, improves data quality and reduces overall development costs.”
In addition, Diurnal is seeking to pave the way for future indication expansion opportunities with Chronocort® through the initiation of a Phase II proof-of-concept study in AI patients. Worldwide will also conduct this Phase II study, which is expected to commence around the end of 2018.
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 overproduction 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 affects approximately 17,000 patients in the US and 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 are at an early stage of development and not expected to receive approval in the short-term.
Diurnal’s Chronocort® has been granted Orphan Drug Designations in Europe and the US for the treatment of CAH, providing the potential to be granted market exclusivity for 10 years in Europe and seven years in the US post market authorization.
About Adrenal Insufficiency
Adrenal insufficiency (AI) is a condition characterized by a deficiency in cortisol, an essential hormone for regulating metabolism and the response to stress. The primary symptoms of AI are chronic fatigue, and patients are at risk of adrenal crisis and death if they do not have adequate cortisol replacement. AI is either primary or secondary, with primary AI resulting from diseases intrinsic to the adrenal gland and secondary AI resulting from pituitary diseases where there is a failure of stimulation of the adrenal by the pituitary of the signalling hormone ACTH (adrenocorticotropic hormone). AI is estimated to affect over four million patients globally.
Diurnal’s Alkindi® and Chronocort® have been granted Orphan Drug Designations in the US for the treatment of AI. Chronocort® also benefits from Orphan Drug Designation for AI in Europe. These orphan drug designations mean Alkindi® and Chronocort® have the potential to be granted market and data exclusivity for seven years in the US and 10 years in Europe for Chronocort® post market authorization.
Chronocort® is a modified release preparation of hydrocortisone 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 upon waking). The first planned indication for Chronocort® is CAH in adults.
Chronocort® has completed three Phase I trials in 2011, 2012 and 2015; a Phase II trial in CAH patients in 2014 in the US; and is currently in a Phase III trial in Europe. This pivotal Phase III trial for Chronocort® in Europe is scheduled to complete in Q3 2018, with market authorization in Europe expected in 2020. In addition, a Phase I NDA-enabling study is currently ongoing.
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 lifelong 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.
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