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