• Acromegaly is an endocrine disorder caused by elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels[1]

  • Signifor LAR (pasireotide) represents a potential new option for acromegaly patients lacking disease control, as measured by both GH and IGF-1 levels[2]

  • Positive CHMP opinion marks critical milestone for Signifor LAR in acromegaly; worldwide regulatory filings are under review by health authorities

Important safety information about Signifor (pasireotide) injection
Signifor is contraindicated in patients with severe hepatic impairment (Child Pugh C).

Hyperglycemia and diabetes occurs with initiation of Signifor therapy. Acromegaly patients with poor glycemic control (as defined by hemoglobin A1c (HbA1c) values >8% while receiving anti-diabetic therapy) may be at a higher risk of developing severe hyperglycemia and associated complications, e.g., ketoacidosis. Intensive glucose monitoring is recommended and may require initiation or adjustment of anti-diabetic treatment.

Treatment with Signifor may lead to bradycardia and QT prolongation. Caution should be used in at-risk patients. ECG testing is recommended prior to dosing and during treatment. Hypokalemia and hypomagnesemia must be corrected prior to Signifor administration and should be monitored periodically during therapy.

Mild transient elevations in aminotransferases are commonly observed in patients treated with pasireotide. Liver tests are recommended prior to and after the first 2 to 3 weeks on treatment, then monthly for 3 months, and as clinically indicated thereafter.

Cholelithiasis is associated with Signifor. Gallbladder ultrasounds should be performed before and at 6- to 12- month intervals.

Inhibition of pituitary hormones may occur with Signifor treatment. Monitoring of pituitary function should occur prior to initiation of therapy and periodically during treatment with Signifor.

Treatment with Signifor may lead to a decrease in circulating levels of cortisol resulting in biochemical and/or clinical hypocortisolism. Signifor dose of reduction or interruption and/or adding low-dose short-term glucocorticoid therapy may be necessary.

Caution is required when co-administering Signifor with anti-arrhythmics and drugs that prolong QT. The following drugs may require monitoring and possible dose adjustments when used with Signifor: cyclosporine, bromocriptine.

The most common adverse reactions (>=10%) occurring in patients in acromegaly clinical trials are hyperglycemia, diabetes mellitus, diarrhea, abdominal pain, cholelithiasis and alopecia.

Please see full Prescribing Information at Signifor.com.

About Sandostatin LAR
Sandostatin LAR, a long-acting, injectable depot formulation of octreotide acetate, is approved in the EU for Treatment of patients with acromegaly in whom surgery is inappropriate or ineffective, or in the interim period until radiotherapy becomes fully effective as per recently finalized label harmonization. In the US, Sandostatin LAR is available as Sandostatin® LAR® Depot for long-term maintenance therapy in patients with acromegaly who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option. The goal of treatment in acromegaly is to reduce GH and IGF-1 levels to normal. Outside the EU and US, acromegaly indications vary by country.

Sandostatin LAR is available from Novartis for different uses and not all indications are available in every country.

Important safety information about Sandostatin LAR (octreotide/IM injection)
Treatment with Sandostatin LAR may affect gallbladder function, sugar metabolism, thyroid and heart function and nutritional absorption, which may require monitoring.

Caution is to be exercised for those with a history of heart disease or taking other medications, including cyclosporine, insulin, oral hypoglycemic agents, beta-blockers and bromocriptine.

Common side effects include diarrhea, gallstones, abdominal pain and flatulence.

Please see full Prescribing Information at Sandostatin.com.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "recommended," "potential," "under review," "positive opinion," "could," "goal," "continued," "commitment," "will," "ongoing," "recommendation," "suggest," "may," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Signifor LAR, or regarding potential future revenues from Signifor LAR or Sandostatin LAR. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Signifor LAR will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Signifor LAR or Sandostatin LAR will be commercially successful in the future. In particular, management's expectations regarding Signifor LAR and Sandostatin LAR could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. 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 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, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 135,000 full-time-equivalent associates and sell products in more than 150 countries around the world. For more information, please visit http://www.novartis.com.

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References
[1] Acromegaly. National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases. 2008 May; 8(3924): 1-10.
[2] Signifor® (pasireotide LAR) Summary of Product Characteristics. Basel, Switzerland: Novartis Pharma AG; September 2014.
[3] Carmichael J.D. et al. Acromegaly Clinical Trial Methodology Impact on Reported Biochemical Efficacy Rates of Somatostatin Receptor Ligan Treatments - a Meta-analysis. J Clin Endocrin Metab. 2014; 99:1825-1833.
[4] RI Health Solutions. "Epidemiology Report for an Orphan Drug Application in the European Union." 2012: 1-17.
[5] European Medicines Agency. "Orphan Designation." Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000029.jsp. Accessed September 2014.
[6] European Medicines Agency. "Public Summary of Positive Opinion of Orphan Designation of Pasireotide for the Treatment of Acromegaly." Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2009/10/WC500006177.pdf. Accessed September 2014.
[7] Gadelha M.R. et al. Superior Efficacy of Pasireotide Versus Continued Treatment with Octreotide or Lanreotide in Patients with Inadequately Controlled Acromegaly: Randomized, Prospective, Phase III Study. The Lancet Diabetes & Endocrinology. 2014 September; http://www.thelancet.com/journals/landia/article/PIIS2213-8587(14)70169-X/fulltext#article_upsell
[8] Rosario P.W. Frequency of Acromegaly in Adults with Diabetes or Glucose Intolerance and Estimated Prevalence in the General Population. Pituitary. 2011; 14: 217-221.
[9] Schneider H et al. A Novel Approach to the Detection of Acromegaly: Accuracy of Diagnosis by Automatic Face Classification. J Clin Endocrin Metab. 2011; 96: 2074-2080.
[10] Holdaway M et al. Factors Influencing Mortality in Acromegaly. J Clin Endocrin Metab. 2004; 89(2): 667-674.
[11] Holdaway I.M. et al. A Meta-Analysis of the Effect of Lowering Serum Levels of GH and IGF-1 on Mortality in Acromegaly. European Journal of Endocrinology. 2009; 159: 89-95.
[12] Colao, et. al. Systemic Complications of Acromegaly: Epidemiology, Pathogenesis, and Management. Endocrine Reviews. 2004; 25:102-152.

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*Lanreotide Autogel (Somatuline®Autogel®) is a registered trademark of Ipsen.

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