Cortendo gains $11M for late-stage Cushing’s study

Cortendo is coming to America. Founded in Sweden, the little biotech has a new CEO who’s building the executive team in the Philadelphia area. And he’s dropping plans for a listing on the Oslo exchange in favor of a U.S. IPO after raising $11 million in bridge financing.

Cortendo CEO Matthew Pauls

The big idea at Cortendo is to take an existing drug–ketoconazole, which is used off-label for Cushing’s disease–and tinker with it to make it safer and more effective. HealthCap, the Third Swedish National Pension Fund (“AP3”), Storebrand and Arctic Fund Management are putting up the venture round. And their money is funding an on-going Phase III study designed to make their case with the FDA.

“It is a nice bridge to the U.S. which also allows us from funding perspective to drive that critically important Phase III to closure,” says CEO Matthew Pauls, an ex-Shire ($SHPG) and Insmed exec from the commercial side of the industry who joined the company a couple of months ago.

Cushing’s is characterized by elevated levels of cortisol, which trigger a host of serious and potentially lethal side effects. The new drug–dubbed COR-003–is designed to hit key enzymes in the cortisol synthesis pathway, using a more targeted segment of ketoconazole.

“We took basically the better half of the molecule and are using it explicitly for Cushing’s syndrome,” says the CEO. Now Cortendo–which is run by a core team of 6, which Pauls plans to expand–will drive for final late-stage data in 2017, setting up a prospective application with the FDA that could allow the company to proceed with plans to create its own commercial operations.

There are about 20,000 to 25,000 Cushing’s patients in the U.S., adds Pauls, with maybe 30,000 to 40,000 in Europe. About half of those patients can expect surgery to address the disease, with the rest candidates for medicinal therapies.

The U.S. represents the company’s largest market opportunity, says Pauls. So it makes sense to drop the Oslo listing in favor of a U.S. exchange. Exactly when that filing could come and where, he adds, hasn’t been determined yet.

– here’s the release


Rare neuroendocrine tumours may be misdiagnosed as Cushing’s disease

By Eleanor McDermid, Senior medwireNews Reporter

Ectopic tumours secreting corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) are very rare in children and can result in a misdiagnosis of Cushing’s disease (CD), say researchers.

Three of the patients in the reported case series had pituitary hyperplasia and underwent transsphenoidal surgery for apparent CD before the tumour that was actually causing their symptoms was located. The hyperplasia was probably caused by release of CRH from the ectopic tumour, which stimulated the pituitary gland, giving the impression of an ACTH-secreting pituitary adenoma, explain Maya Lodish (National Institutes of Health, Bethesda, Maryland, USA) and study co-authors.

These three patients were part of a series of seven, which Lodish et al describe as “a relatively large number of patients, considering the infrequency of this disease.”

The patients were aged between 1.8 and 21.3 years. Three had neuroendocrine tumours located in the pancreas ranging in size from 1.4 to 7.0 cm, two had thymic carcinoids ranging from 6.0 mm to 11.5 cm, one patient had a 12.0 cm tumour in the liver and one had a 1.3 cm bronchogenic carcinoid tumour of the right pulmonary lobe.

Four of the patients had metastatic disease and, during up to 57 months of follow-up, three died of metastatic disease or associated complications and two patients had recurrent disease.

“Our series demonstrates that these are aggressive tumors with a high mortality rate,” write the researchers in the Journal of Clinical Endocrinology & Metabolism. “It is important to follow the appropriate work up, regarding both biochemical and imaging tests, which can lead to the correct diagnosis and to the most beneficial therapeutic approach.”

The team found the CRH stimulation test to be helpful, noting, for example, that none of the patients had a rise in cortisol that was consistent with CD, with all patients showing smaller responses ranging from 2% to 15%. Likewise, just one patient had an ACTH rise higher than 35% on CRH administration, and four patients had a “flat” response, which has previously been associated with ectopic neuroendocrine tumours.

Of note, six patients had normal or high plasma CRH levels, despite all having high cortisol levels, which would be expected to result in undetectable plasma CRH due to negative feedback, implying another source of CRH production. Five patients had blunted diurnal variation of both cortisol and ACTH levels consistent with Cushing’s syndrome.

The patients also underwent a variety of imaging procedures to identify the source of ACTH/CRH production, some of which, such as octreotide scans, are specialist and not available in most hospitals, the researchers note, potentially contributing to inappropriate diagnosis and management.


Safety of DR-HC for adrenal insufficiency

Conventional treatment of adrenal insufficiency involves cortisol replacement therapy with twice- or thrice-daily oral hydrocortisone. Recently dual-release hydrocortisone (DR-HC) administered once daily to provide high levels of cortisol during the morning, followed by a gradual decrease throughout the day is being used. This results in considerably lower cortisol exposure during the afternoon and evening compared with immediate-release thrice-daily hydrocortisone, thereby mimicking normal cortisol secretion more closely than conventional therapy.

Nilsson et al. conducted a study to evaluate the long-term safety of DR-HC and whether the difference in the incidence of adverse events persisted over time and if it was related to different levels of exposure to cortisol. They conducted a randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. The results of the study of the newly developed DR-HC showed that long-term maintenance treatment and rescue therapy was well tolerated up to 27 months of continuous treatment.

Read full article titled ‘Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency’ by Nilsson et al., European Journal of Endocrinology 171 pp 369 – 377, DOI: 10.1530/EJE-14-0327

Cushing Syndrome in Children: Growth after Surgical Cure

Cushing syndrome (CS) occurs only rarely in children, but when it does, it causes weight gain and stunting. In young children, adrenal tumors are usually the cause while in adolescents, pituitary tumors are more likely.

The September 2014 issue of Endocrine-Related Cancer examines growth patterns in 19 pediatric patients with ACTH-dependent CS (CD) and 18 patients with a form of ACTH-independent CS, micronodular adrenal hyperplasia (MAH). The researchers gathered data at the time of surgery and also followed up one year later.

Patients in the CD and the MAH groups had similar demographic characteristics, baseline heights and BMI scores before surgery. All patients experienced significant improvements in height and BMI after surgery. Patients with MAH, however, fared significantly better than those with CD and had better post-operative growth.

The researchers propose several reasons:

  • When ACTH-secreting pituitary adenoma requires extensive surgical exploration, remaining pituitary cells often lose some of their function.
  • CD patients tend to be older and have consistent and increased glucocorticoid exposure; they develop vertebral fractures more often leading to compromised skeletal and overall growth potential. MAH patients often have cyclical CS, with intermittent hypercortisolism and an overall milder CS.
  • CD patients often need a longer-than-expected course of therapy with steroids after surgery, which alters metabolism and growth.
  • CD patients have been shown to have advance bone age because of ACTH-induced metabolic changes.

The authors indicate that CS patients are often considered for growth hormone therapy once the underlying problem is corrected. They remind clinicians that MAH patients are less likely to need growth hormone. They recommend close monitoring for CD patients, and early intervention with growth hormone if growth does not meet expectation. –

See more at:

Webinar: Hypothalamic Pituitary Dysfunction in Young Athletes with Head Injury (THI)

Don’t miss this great opportunity.
Join us tomorrow for a free webinar!

Date: October 23, 2014
Time: 12:00 – 1:00 PM Pacific Daylight Time

Hypothalamic Pituitary Dysfunction in Young Athletes with Head Injury (THI)
Presented by: Saad Sakkal, MD, FACP, FACE, FACPE
Director, Metabolic Care Center, Mason, Ohio

Traumatic brain Injury has been recently of great attraction to researchers, retired football players, and the public. But years before it is documented clinically the Hypothalamic pituitary Dysfunction symptoms appear at much earlier age and need more vigorous attention.

We present in this webinar the early symptoms and recognition of the syndrome from clinical perspective. Describe the Hypothalamic Dysfunction in its widest picture, its relation to Fibromyalgia/Chronic fatigue, and its present therapy available .

If you are unable to attend the live webinar, we will have it available on our website starting Monday. I will post a link when it is available.

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