Click here to close now.

Welcome!

Agile Computing Authors: Harry Trott, Lacey Thoms, Liz McMillan, Adrian Bridgwater, Pat Romanski

News Feed Item

Novartis drug Signifor® gains FDA approval as the first medication to treat Cushing's disease, a serious endocrine disorder

- As the only pituitary-directed therapy, Signifor represents a novel therapeutic approach by addressing the underlying mechanism of Cushing's disease(1)

EAST HANOVER, N.J., Dec. 14, 2012 /PRNewswire/ -- Novartis announced today that the US Food and Drug Administration (FDA) has approved 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 curative3. 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 tumor which ultimately leads to excess cortisol in the body1,4. 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 Herve 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 population1,4,5,6,7.

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 disease3. 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 improve2.

"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 Signifor for 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.

About Cushing's disease
Cushing's syndrome is an endocrine disorder caused by excessive cortisol, a vital hormone that regulates metabolism, maintains cardiovascular function and helps the body respond to stress. Cushing's disease is a form of Cushing's syndrome, in which excess cortisol production is triggered by a pituitary adenoma secreting excess adrenocorticotropic hormone (ACTH). It is a rare but serious disease that affects approximately one to two patients per million per year. The first line and most common treatment approach for Cushing's disease is surgical removal of the tumor4,6,8.

About PASPORT-CUSHINGS
PASPORT-CUSHINGS is a prospective, randomized, double-blind, Phase III study conducted at 68 sites in 18 countries. The study evaluated the efficacy and safety of Signifor in 162 adult patients with persistent or recurrent Cushing's disease, as well as in patients with newly diagnosed Cushing's disease who were not candidates for surgery2.

Patients with UFC levels greater than 1.5 times the upper limit of normal (ULN) were randomized to receive Signifor subcutaneous (sc) injection in doses of 0.9 mg (n=80) or 0.6 mg (n=82) twice daily2.

The primary endpoint, the proportion of patients who achieved normalization of UFC after six months without dose up-titration relative to randomized dose, was met in patients treated with 0.9 mg twice daily. Mean UFC levels were normalized in 26% and 15% of the patients randomized to receive Signifor 0.9 mg and 0.6 mg, respectively, at month six2.

The median reduction in mean UFC from baseline to month six was around 47% in both dose groups. Reductions in UFC were observed after one month of treatment with Signifor and were sustained during the treatment period in most patients. In addition, 34% and 41% of patients experienced a reduction in mean UFC from baseline less than or equal to ULN or greater than or equal to 50% in the 0.6 mg and 0.9 mg groups, respectively2.

Decreases in blood pressure, weight, body mass index and waist circumference were observed during the study. Limited conclusions can be drawn on these decreases due to variability of response across patients and the absence of a control group2.

The most common adverse events (AE) (greater than or equal to 20%) occurring in patients in either dose group receiving Signifor were diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue and diabetes mellitus. The safety profile of Signifor was similar to that of other somatostatin analogs with the exception of the greater degree of hyperglycemia2.

About Signifor (pasireotide)
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.

Signifor is expected to be available in the US by March 2013 and will be dispensed exclusively through a single specialty pharmacy. For more information about Signifor distribution, doctors and patients can contact Patient Assistance Now Endocrinology (PAN Endo) at 1-877-503-3377 (Press Option 3 for Signifor) or visit www.Signifor.us for more information. PAN Endo also offers quick and easy access to information about the many reimbursement and support programs available for its endocrinology medicines. Enrollment into PAN Endo will begin in January 2013.

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)6,9,10.

Important Safety Information about Signifor
Treatment with Signifor leads to suppression of adrenocorticotropic hormone (ACTH) secretion in Cushing's disease patients. Suppression of ACTH may lead to a decrease in circulating levels of cortisol and potentially hypocortisolism. Patients need to be monitored and instructed how to monitor for signs and symptoms of hypocortisolism. Temporary exogenous steroid (glucocorticoid) replacement therapy and/or dose reduction or interruption of Signifor therapy may be necessary.

Elevations in blood glucose levels have been frequently reported in healthy volunteers and patients treated with Signifor. Cushing's disease patients with poor glycemic control may be at higher risk of developing severe hyperglycemia and associated complications. Glycemic status should be assessed prior to starting treatment with Signifor. Patients need to be closely monitored for hyperglycemia; if hyperglycemia develops, the initiation or adjustment of antidiabetic treatment is recommended. Dose reduction or treatment discontinuation should be considered if uncontrolled hyperglycemia persists. After treatment discontinuation, glycemic monitoring (e.g., FPG or HbA1c) should be done according to clinical practice.

Bradycardia has been reported with use of Signifor. Patients with cardiac disease and/or risk factors for bradycardia need to be closely monitored. Signifor is associated with QT prolongation. Caution should be exercised in patients who have or may develop QT prolongation. Hypokalemia or hypomagnesemia must be corrected prior to initiating therapy and monitored thereafter. A baseline electrocardiogram should be performed prior to the start of Signifor therapy and monitoring for an effect on QTc interval is advisable during therapy.

Elevations in AST (aminotransferases) or ALT (alanine aminotransferase) were reported with the use of Signifor. Monitoring of liver function is recommended prior to starting treatment with Signifor. Liver function should be monitored again after one or two weeks on treatment, then monthly for the first three months and every six months thereafter. Therapy should be discontinued if AST or ALT increase five times the upper limit of normal or greater.

Cholelithiasis has been frequently reported with the use of Signifor. Ultrasonic evaluation of the gallbladder prior to treatment, and thereafter at six and 12 month intervals is recommended. 

Monitoring of pituitary hormones is recommended prior to initiating treatment and periodically thereafter as clinically appropriate.

Signifor should not be used during pregnancy unless medically necessary. Breast feeding should be discontinued during treatment with Signifor.

Signifor may affect the way other medicines work, and other medicines can affect how Signifor works. Caution should be exercised with the concomitant use of bromocriptine, cyclosporine, anti-arrhythmic medicines or drugs that may lead to QT prolongation.

The most common adverse events (AE) (greater than or equal to 20%) occurring in patients in either dose group receiving Signifor were diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue and diabetes mellitus.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "underway," "commitment," "will," "expected," "can," or similar expressions, or by express or implied discussions regarding potential additional marketing approvals for Signifor or regarding potential future revenues from Signifor. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Signifor to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Signifor will be approved for sale in any additional markets, or at any particular time. Nor can there be any guarantee that Signifor will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Signifor could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; unexpected manufacturing issues; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets innovative prescription drugs used to treat a number of diseases and conditions, including cardiovascular, dermatological, central nervous system, bone disease, cancer, organ transplantation, psychiatry, infectious disease and respiratory. The company's mission is to improve people's lives by pioneering novel healthcare solutions.

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2011, the Group's continuing operations achieved net sales of USD 58.6 billion, while approximately USD 9.6 billion (USD 9.2 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Novartis Group companies employ approximately 127,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis.

References

1.  Novartis Briefing Information for the November 7, 2012 Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM326812.pdf. Accessed November 2012.

2.  Colao, A. A 12-Month Phase III Study of Pasireotide in Cushing's Disease. New Engl J Med. 2012; 366(10):914-924.

3.  Signifor® (pasireotide) Prescribing Information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; December 2012.

4.  National Endocrine and Metabolic Diseases Information Service. US National Institutes of Health. Cushing's Syndrome. Available at: http://endocrine.niddk.nih.gov/pubs/cushings/Cushings_Syndrome_FS.pdf. Accessed October 2012.

5.  Newell-Price, J., et al. The Diagnosis and Differential Diagnosis of Cushing's Syndrome and Pseudo-Cushing's States. Endocrine Reviews.1998;19(5):647-672.

6.  Pedroncelli, A. Medical Treatment of Cushing's Disease: Somatostatin Analogues and Pasireotide. Neuroendocrinology. 2010;92(suppl1):120-124.

7.  Extabe, J. and Valquez E. Morbidity and Mortality in Cushing's Disease: An Epidemiological Approach. Clinical Endocrinology. 1994;40:479-484.

8.  Lindholm, J., et al. Incidence and Late Prognosis of Cushing's Syndrome: A Population-Based Study. J Clin Endocrinol Metab. 2001;86(1):117-23.

9.  US National Institutes of Health. Safety and Efficacy of Pasireotide Long Acting Release (LAR) vs. Octreotide LAR in Patients With Active Acromegaly. Available at: http://clinicaltrials.gov/ct2/show/NCT00600886?term=safety+and+efficacy+of+pasireotide&rank=3. Accessed October 2012.

10.  US National Institutes of Health. Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease. Available at: http://clinicaltrials.gov/ct2/show/NCT01374906. Accessed October 2012.

Novartis Media Relations

Julie Masow

Novartis Corporation

+1 212 830 2465 (direct)

+1 862 579 8456 (mobile)

[email protected]

 

e-mail: [email protected]

Nicole Riley

Novartis Oncology

+1 862 778 3110 (direct)

+1 862 926 9040 (mobile)

[email protected]

 

For Novartis multimedia content, please visit www.thenewsmarket.com/Novartis.
For questions about the site or required registration, please contact: [email protected].

 

SOURCE Novartis

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

@ThingsExpo Stories
The 4th International Internet of @ThingsExpo, co-located with the 17th International Cloud Expo - to be held November 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA - announces that its Call for Papers is open. The Internet of Things (IoT) is the biggest idea since the creation of the Worldwide Web more than 20 years ago.
The Internet of Things is a misnomer. That implies that everything is on the Internet, and that simply should not be - especially for things that are blurring the line between medical devices that stimulate like a pacemaker and quantified self-sensors like a pedometer or pulse tracker. The mesh of things that we manage must be segmented into zones of trust for sensing data, transmitting data, receiving command and control administrative changes, and peer-to-peer mesh messaging. In his session at @ThingsExpo, Ryan Bagnulo, Solution Architect / Software Engineer at SOA Software, focused on desi...
An entirely new security model is needed for the Internet of Things, or is it? Can we save some old and tested controls for this new and different environment? In his session at @ThingsExpo, New York's at the Javits Center, Davi Ottenheimer, EMC Senior Director of Trust, reviewed hands-on lessons with IoT devices and reveal a new risk balance you might not expect. Davi Ottenheimer, EMC Senior Director of Trust, has more than nineteen years' experience managing global security operations and assessments, including a decade of leading incident response and digital forensics. He is co-author of t...
The multi-trillion economic opportunity around the "Internet of Things" (IoT) is emerging as the hottest topic for investors in 2015. As we connect the physical world with information technology, data from actions, processes and the environment can increase sales, improve efficiencies, automate daily activities and minimize risk. In his session at @ThingsExpo, Ed Maguire, Senior Analyst at CLSA Americas, will describe what is new and different about IoT, explore financial, technological and real-world impact across consumer and business use cases. Why now? Significant corporate and venture...
Today’s enterprise is being driven by disruptive competitive and human capital requirements to provide enterprise application access through not only desktops, but also mobile devices. To retrofit existing programs across all these devices using traditional programming methods is very costly and time consuming – often prohibitively so. In his session at @ThingsExpo, Jesse Shiah, CEO, President, and Co-Founder of AgilePoint Inc., discussed how you can create applications that run on all mobile devices as well as laptops and desktops using a visual drag-and-drop application – and eForms-buildi...
While great strides have been made relative to the video aspects of remote collaboration, audio technology has basically stagnated. Typically all audio is mixed to a single monaural stream and emanates from a single point, such as a speakerphone or a speaker associated with a video monitor. This leads to confusion and lack of understanding among participants especially regarding who is actually speaking. Spatial teleconferencing introduces the concept of acoustic spatial separation between conference participants in three dimensional space. This has been shown to significantly improve comprehe...
There will be 150 billion connected devices by 2020. New digital businesses have already disrupted value chains across every industry. APIs are at the center of the digital business. You need to understand what assets you have that can be exposed digitally, what their digital value chain is, and how to create an effective business model around that value chain to compete in this economy. No enterprise can be complacent and not engage in the digital economy. Learn how to be the disruptor and not the disruptee.
The enterprise market will drive IoT device adoption over the next five years. In his session at @ThingsExpo, John Greenough, an analyst at BI Intelligence, division of Business Insider, will analyze how companies will adopt IoT products and the associated cost of adopting those products. John Greenough is the lead analyst covering the Internet of Things for BI Intelligence- Business Insider’s paid research service. Numerous IoT companies have cited his analysis of the IoT. Prior to joining BI Intelligence, he worked analyzing bank technology for Corporate Insight and The Clearing House Pay...
SYS-CON Events announced today that MetraTech, now part of Ericsson, has been named “Silver Sponsor” of SYS-CON's 16th International Cloud Expo®, which will take place on June 9–11, 2015, at the Javits Center in New York, NY. Ericsson is the driving force behind the Networked Society- a world leader in communications infrastructure, software and services. Some 40% of the world’s mobile traffic runs through networks Ericsson has supplied, serving more than 2.5 billion subscribers.
With major technology companies and startups seriously embracing IoT strategies, now is the perfect time to attend @ThingsExpo in Silicon Valley. Learn what is going on, contribute to the discussions, and ensure that your enterprise is as "IoT-Ready" as it can be! Internet of @ThingsExpo, taking place Nov 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 17th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The Internet of Things (IoT) is the most profound change in personal an...
The Domain Name Service (DNS) is one of the most important components in networking infrastructure, enabling users and services to access applications by translating URLs (names) into IP addresses (numbers). Because every icon and URL and all embedded content on a website requires a DNS lookup loading complex sites necessitates hundreds of DNS queries. In addition, as more internet-enabled ‘Things' get connected, people will rely on DNS to name and find their fridges, toasters and toilets. According to a recent IDG Research Services Survey this rate of traffic will only grow. What's driving t...
The Internet of Things promises to transform businesses (and lives), but navigating the business and technical path to success can be difficult to understand. In his session at @ThingsExpo, Sean Lorenz, Technical Product Manager for Xively at LogMeIn, demonstrated how to approach creating broadly successful connected customer solutions using real world business transformation studies including New England BioLabs and more.
The world is at a tipping point where the technology, the device and global adoption are converging to such a point that we will see an explosion of a world where smartphone devices not only allow us to talk to each other, but allow for communication between everything – serving as a central hub from which we control our world – MediaTek is at the heart of both driving this and allowing the markets to drive this reality forward themselves. The next wave of consumer gadgets is here – smart, connected, and small. If your ambitions are big, so are ours. In his session at @ThingsExpo, Jack Hu, D...
17th Cloud Expo, taking place Nov 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy. Meanwhile, 94% of enterprises are using some form of XaaS – software, platform, and infrastructure as a service.
The recent trends like cloud computing, social, mobile and Internet of Things are forcing enterprises to modernize in order to compete in the competitive globalized markets. However, enterprises are approaching newer technologies with a more silo-ed way, gaining only sub optimal benefits. The Modern Enterprise model is presented as a newer way to think of enterprise IT, which takes a more holistic approach to embracing modern technologies.
The true value of the Internet of Things (IoT) lies not just in the data, but through the services that protect the data, perform the analysis and present findings in a usable way. With many IoT elements rooted in traditional IT components, Big Data and IoT isn’t just a play for enterprise. In fact, the IoT presents SMBs with the prospect of launching entirely new activities and exploring innovative areas. CompTIA research identifies several areas where IoT is expected to have the greatest impact.
There's no doubt that the Internet of Things is driving the next wave of innovation. Google has spent billions over the past few months vacuuming up companies that specialize in smart appliances and machine learning. Already, Philips light bulbs, Audi automobiles, and Samsung washers and dryers can communicate with and be controlled from mobile devices. To take advantage of the opportunities the Internet of Things brings to your business, you'll want to start preparing now.
P2P RTC will impact the landscape of communications, shifting from traditional telephony style communications models to OTT (Over-The-Top) cloud assisted & PaaS (Platform as a Service) communication services. The P2P shift will impact many areas of our lives, from mobile communication, human interactive web services, RTC and telephony infrastructure, user federation, security and privacy implications, business costs, and scalability. In his session at @ThingsExpo, Robin Raymond, Chief Architect at Hookflash, will walk through the shifting landscape of traditional telephone and voice services ...
Explosive growth in connected devices. Enormous amounts of data for collection and analysis. Critical use of data for split-second decision making and actionable information. All three are factors in making the Internet of Things a reality. Yet, any one factor would have an IT organization pondering its infrastructure strategy. How should your organization enhance its IT framework to enable an Internet of Things implementation? In his session at Internet of @ThingsExpo, James Kirkland, Chief Architect for the Internet of Things and Intelligent Systems at Red Hat, described how to revolutioniz...
The security devil is always in the details of the attack: the ones you've endured, the ones you prepare yourself to fend off, and the ones that, you fear, will catch you completely unaware and defenseless. The Internet of Things (IoT) is nothing if not an endless proliferation of details. It's the vision of a world in which continuous Internet connectivity and addressability is embedded into a growing range of human artifacts, into the natural world, and even into our smartphones, appliances, and physical persons. In the IoT vision, every new "thing" - sensor, actuator, data source, data con...