Monday, December 17, 2012

US FDA approves Novartis' Signifor for first medication to treat Cushing's disease


Monday, December 17, 2012, 16:00 Hrs  [IST]


The US Food and Drug Administration (FDA) has approved Novartis' Signifor (pasireotide) injection for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative. 


Signifor is the first medicine to be approved in the US that addresses the underlying mechanism of Cushing's disease, a serious, debilitating endocrine disorder caused by the presence of a non-cancerous pituitary tumour which ultimately leads to excess cortisol in the body.


This approval follows a unanimous recommendation from the FDA Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) in support of the use of Signifor.


"The FDA approval of Signifor for Cushing's disease brings a novel pituitary-directed therapy to patients with limited treatment options," said Hervé Hoppenot, president, Novartis Oncology. "Today's milestone reinforces Novartis' commitment to addressing unmet needs and advancing treatments for rare pituitary-related disorders."


Cushing's disease most commonly affects adults as young as 20 to 50 years and affects women three times more often than men. It may present with weight gain, central obesity, a round, red full face, severe fatigue and weakness, striae (purple stretch marks), high blood pressure, depression and anxiety. Cushing's disease can cause severe illness and death with mortality up to four times higher than in the healthy population.


The approval is based on data from PASPORT-CUSHINGS (PASireotide clinical trial PORTfolio - CUSHING'S disease), the largest randomized Phase III study to evaluate a medical therapy in patients with Cushing's disease. Results from the PASPORT-CUSHINGS study found that a decrease in mean urinary-free cortisol (UFC), the key measure of biochemical control of the disease, was sustained during the treatment period in most patients with a subset of patients reaching normal levels. The study also showed that certain clinical manifestations of Cushing's disease tended to improve.


"Patients with Cushing's disease may suffer from debilitating manifestations, and there are many serious health complications associated with the disease," said Mary Andrews, CEO and Co-Founder of the US non-profit, The MAGIC Foundation. "The FDA approval of Signifor offers the option of a medical therapy that may help certain patients with Cushing's disease."


In April 2012, the European Commission approved Signiforfor the treatment of adult patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed. Other worldwide regulatory filings for pasireotide for this use are also underway.

Signifor (pasireotide) is approved in the US for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative, and in the European Union for the treatment of adult patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed.


For the treatment of Cushing's disease, Signifor has been studied as a twice-daily subcutaneous (sc) injection and is currently being evaluated as a long-acting release (LAR), once-monthly intramuscular (IM) injection as part of a global Phase III program in Cushing's disease and acromegaly. Signifor is a multireceptor targeting somatostatin analog that binds with high affinity to four of the five somatostatin receptor subtypes (sst 1, 2, 3 and 5).



Thursday, December 6, 2012

RARE Video Project

Global Genes | RARE Project would like your voice to be heard!

Share your home videos!

We are currently looking for your home videos that illustrate what life is like for rare disease patients and caregivers on this complex and often emotional journey.  This could be an assortment of moments that you’ve captured on your phone, a camera, or a digital recording device.  We want the key moments, the most beautiful, personal moments that represent not only the diseases, but you and your child(ren) as well.

A few examples of what we are looking for in these clips:


In Pain





Hospital Visits





Important Events

At Play



Be creative, think outside the box.   Look for clips that are shot well, with nice light.  Give us variety!  Old footage, new footage, maybe even something your child has shot.  We want personal, private moments.  That is what will send the strongest message.

What are we going to do with this?

We are working with an award-winning filmmaking team to select submissions that will be compiled together to create a visual storyline of the years of your ongoing journey.  This is your chance to share the moments that you see and experience with a global audience.

This is your moment to be heard.

More information at

Cushing Syndrome Overview

Cushing’s syndrome (pronounced KOOSH-ingz SIN-drohm) is a condition that occurs when a person’s body tissues are exposed over time to too much of the hormone cortisol (pronouncedKAWR-tuh-sawl). The syndrome can be caused by taking certain medicines or, less commonly, it can be caused by noncancerous or cancerous tumors. Cushing’s syndrome includes a range of symptoms, but they can be treated and, in most cases, the syndrome can be cured. The NICHD is one of the many federal agencies that support and conduct research on the causes of Cushing’s syndrome, detection of its symptoms as soon as possible, and development of improved treatments.

For more information about this topic, select the Condition Information, Research Information, Clinical Trials, or Resources and Publications link in the menu on the left.

Fast Facts

Common Name

  • Cushing's syndrome

Scientific Name

  • Hyperadrenocorticism (pronounced HAHY-per-uh-dree-noh-KAWR-ti-siz-uhm)
  • Hypercortisolism (pronounced HAHY-per-KAWR-ti-sol-iz-uhm)


The most common cause of Cushing’s syndrome is taking medication that contains the hormone cortisol. This leaves the body with more cortisol than it would normally contain from the natural production of cortisol.1 Less commonly, a cancerous or noncancerous tumor in the body can cause too much cortisol production.2

Number of People Affected

Among 1 million people, two or three will develop endogenous (non-medicine-related) Cushing’s syndrome each year in the United States.3 Women are three times more likely than men to have the condition.4

Common Symptoms

The symptoms of Cushing’s syndrome vary, especially in mild cases, but patients may have some or most of the following1:

  • Upper-body obesity, with thin arms and legs
  • A round, red face
  • Skin problems, such as acne, reddish-blue streaks, or easy bruising
  • Muscle and bone weakness, including backache
  • Fat that collects between the shoulders
  • Poor growth in children5

Common Treatments

In most cases Cushing’s syndrome can be cured. The treatment depends on what is causing the excess cortisol in the body.6,7

Cushing’s syndrome can be treated by the following:

  • Medication. If medication is to blame, a health care provider can reduce the dose or change the type of drug.
  • Overproduction. If the body is making too much cortisol because of a tumor, treatments may include oral medication, surgery, radiation, or a combination of these approaches.


  1. Stewart P. M., & Krone, N. P. (2011). The adrenal cortex. In Kronenberg, H. M., Shlomo, M., Polonsky, K. S., & Larsen, P. R. (Eds.). Williams textbook of endocrinology (12th ed.) (chap. 15). Philadelphia, PA: Saunders Elsevier. [top]
  2. Nieman, L. K., & Ilias, I. (2005) Evaluation and treatment of Cushing’s syndrome. Journal of American Medicine, 118(12), 1340-1346. PMID 16378774. [top]
  3. Lindholm, J., Juul, S., Jørgensen, J. O. L, Astrup, J., Bjerre, P., Feldt-Rasmussen, U., et al. (2001). Incidence and late prognosis of Cushing’s syndrome: A population-based study. Journal of Clinical Endocrinology and Metabolism, 86(1), 117-123. PMID 11231987[top]
  4. Steffensen, C., Bak, A. M., Rubeck, K. Z., & Jørgensen, J. O. (2010). Epidemiology of Cushing’s syndrome. Neuroendocrinology, 92(Suppl 1), 1-5. PMID 20829610[top]
  5. Batista, D. L., Riar, J., Keil, M., & Stratakis, C.A. (2007). Diagnostic tests for children who are referred for the investigation of Cushing syndrome. Pediatrics120(3), e575-e586. [top]
  6. Nieman, L. K., Biller, B. M. K., Findling, J. W., Newell-Price, J., Savage, M. O., et al. (2008). The diagnosis of Cushing’s syndrome: An Endocrine Society clinical practice guideline. Retrieved April 8, 2012, from (PDF - 510 KB). [top]
  7. Boscaro, M., & Arnaldi, G. (2009). Approach to the patient with possible Cushing’s syndrome. Journal of Clinical Endocrinology and Metabolism, 94(9), 3121. [top]


Last Updated Date: 11/30/2012
Last Reviewed Date: 11/30/2012

Tuesday, December 4, 2012

Mifepristone: is there a place in the treatment of Cushing's disease?

Carmichael JD, Fleseriu M.


Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA,


The purpose was to review the use of mifepristone in the treatment of Cushing's syndrome (CS) in the context of other recently published studies. We review the use of mifepristone, as published in the recent Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC). We also review the multiple case reports and case series of mifepristone use in CS. A review of other medications used in the treatment of Cushing's disease (CD), including pasireotide and cabergoline also provides context for the discussion of the role of mifepristone in the treatment of CD. The results show that the treatment of CD has been primarily surgical with medical therapy reserved for adjuvant therapy when primary treatment fails or other therapies require time for optimal efficacy. Two recent large prospective studies, using pasireotide and mifepristone provide new clinical insights to the medical treatment of CD in particular. Mifepristone has been used to treat excessive cortisol production by blocking the action of cortisol at the level of the glucocorticoid receptor. Until recently, the majority of clinical experience with mifepristone on the treatment of excess cortisol was derived from case reports and small case series. Based on the SEISMIC study, mifepristone was FDA approved for hyperglycemia associated with CS. In conclusion the role of mifepristone in the treatment of CD remains one of adjuvant therapy. Its place among other choices for medical therapy has yet to be firmly established and an evidenced-based approach toward the use of novel medications in the treatment of CD has not been made. Selection of medication depends on drug approval and availability in individual countries and requires cautious assessment of potential adverse effects, consideration of patient comorbidities, and efficacy.


PMID: 23192246 [PubMed - as supplied by publisher]