|By PR Newswire||
|December 14, 2012 08:27 PM EST||
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.
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.
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.
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.
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
+1 212 830 2465 (direct)
+1 862 579 8456 (mobile)
e-mail: [email protected]
+1 862 778 3110 (direct)
+1 862 926 9040 (mobile)
In today's uber-connected, consumer-centric, cloud-enabled, insights-driven, multi-device, global world, the focus of solutions has shifted from the product that is sold to the person who is buying the product or service. Enterprises have rebranded their business around the consumers of their products. The buyer is the person and the focus is not on the offering. The person is connected through multiple devices, wearables, at home, on the road, and in multiple locations, sometimes simultaneously...
Jul. 31, 2016 01:30 AM EDT Reads: 989
Basho Technologies has announced the latest release of Basho Riak TS, version 1.3. Riak TS is an enterprise-grade NoSQL database optimized for Internet of Things (IoT). The open source version enables developers to download the software for free and use it in production as well as make contributions to the code and develop applications around Riak TS. Enhancements to Riak TS make it quick, easy and cost-effective to spin up an instance to test new ideas and build IoT applications. In addition to...
Jul. 31, 2016 12:45 AM EDT Reads: 2,041
Identity is in everything and customers are looking to their providers to ensure the security of their identities, transactions and data. With the increased reliance on cloud-based services, service providers must build security and trust into their offerings, adding value to customers and improving the user experience. Making identity, security and privacy easy for customers provides a unique advantage over the competition.
Jul. 30, 2016 11:30 PM EDT Reads: 1,338
CenturyLink has announced that application server solutions from GENBAND are now available as part of CenturyLink’s Networx contracts. The General Services Administration (GSA)’s Networx program includes the largest telecommunications contract vehicles ever awarded by the federal government. CenturyLink recently secured an extension through spring 2020 of its offerings available to federal government agencies via GSA’s Networx Universal and Enterprise contracts. GENBAND’s EXPERiUS™ Application...
Jul. 30, 2016 10:30 PM EDT Reads: 1,944
"We've discovered that after shows 80% if leads that people get, 80% of the conversations end up on the show floor, meaning people forget about it, people forget who they talk to, people forget that there are actual business opportunities to be had here so we try to help out and keep the conversations going," explained Jeff Mesnik, Founder and President of ContentMX, in this SYS-CON.tv interview at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
Jul. 30, 2016 09:45 PM EDT Reads: 1,497
SYS-CON Events announced today that Isomorphic Software will exhibit at DevOps Summit at 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Isomorphic Software provides the SmartClient HTML5/AJAX platform, the most advanced technology for building rich, cutting-edge enterprise web applications for desktop and mobile. SmartClient combines the productivity and performance of traditional desktop software with the simp...
Jul. 30, 2016 09:45 PM EDT Reads: 1,320
"When you think about the data center today, there's constant evolution, The evolution of the data center and the needs of the consumer of technology change, and they change constantly," stated Matt Kalmenson, VP of Sales, Service and Cloud Providers at Veeam Software, in this SYS-CON.tv interview at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
Jul. 30, 2016 09:30 PM EDT Reads: 1,533
Redis is not only the fastest database, but it is the most popular among the new wave of databases running in containers. Redis speeds up just about every data interaction between your users or operational systems. In his session at 19th Cloud Expo, Dave Nielsen, Developer Advocate, Redis Labs, will share the functions and data structures used to solve everyday use cases that are driving Redis' popularity.
Jul. 30, 2016 07:30 PM EDT Reads: 1,768
I wanted to gather all of my Internet of Things (IOT) blogs into a single blog (that I could later use with my University of San Francisco (USF) Big Data “MBA” course). However as I started to pull these blogs together, I realized that my IOT discussion lacked a vision; it lacked an end point towards which an organization could drive their IOT envisioning, proof of value, app dev, data engineering and data science efforts. And I think that the IOT end point is really quite simple…
Jul. 30, 2016 07:30 PM EDT Reads: 1,320
Internet of @ThingsExpo, taking place November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with the 19th International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world and ThingsExpo Silicon Valley Call for Papers is now open.
Jul. 30, 2016 07:00 PM EDT Reads: 2,777
You think you know what’s in your data. But do you? Most organizations are now aware of the business intelligence represented by their data. Data science stands to take this to a level you never thought of – literally. The techniques of data science, when used with the capabilities of Big Data technologies, can make connections you had not yet imagined, helping you discover new insights and ask new questions of your data. In his session at @ThingsExpo, Sarbjit Sarkaria, data science team lead ...
Jul. 30, 2016 05:00 PM EDT Reads: 1,311
To leverage Continuous Delivery, enterprises must consider impacts that span functional silos, as well as applications that touch older, slower moving components. Managing the many dependencies can cause slowdowns. See how to achieve continuous delivery in the enterprise.
Jul. 30, 2016 04:30 PM EDT Reads: 588
WebRTC is bringing significant change to the communications landscape that will bridge the worlds of web and telephony, making the Internet the new standard for communications. Cloud9 took the road less traveled and used WebRTC to create a downloadable enterprise-grade communications platform that is changing the communication dynamic in the financial sector. In his session at @ThingsExpo, Leo Papadopoulos, CTO of Cloud9, discussed the importance of WebRTC and how it enables companies to focus...
Jul. 30, 2016 04:30 PM EDT Reads: 1,128
"My role is working with customers, helping them go through this digital transformation. I spend a lot of time talking to banks, big industries, manufacturers working through how they are integrating and transforming their IT platforms and moving them forward," explained William Morrish, General Manager Product Sales at Interoute, in this SYS-CON.tv interview at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
Jul. 30, 2016 04:30 PM EDT Reads: 2,283
Up until last year, enterprises that were looking into cloud services usually undertook a long-term pilot with one of the large cloud providers, running test and dev workloads in the cloud. With cloud’s transition to mainstream adoption in 2015, and with enterprises migrating more and more workloads into the cloud and in between public and private environments, the single-provider approach must be revisited. In his session at 18th Cloud Expo, Yoav Mor, multi-cloud solution evangelist at Cloudy...
Jul. 30, 2016 04:15 PM EDT Reads: 661