Omega-3 Meds Not Effective After MI, EMA Panel Concludes


The European Medicine Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) has concluded that omega-3 fatty acid medicines are not effective for secondary prevention after myocardial infarction (MI).

Omega-3 fatty acid medicines at a dose of 1 g per day have been authorized in several European Union countries since 2000 for preventing heart disease or stroke after MI and for lowering high triglycerides.

When they were authorized, the available data showed “some benefits in reducing serious problems with the heart and blood vessels, although the benefits were considered modest,” the EMA said in a news release. “Further data that have become available since then have not confirmed the beneficial effects of these medicines for this use.”

The CHMP’s conclusion, released at their December meeting, means that these medicines will no longer be authorized for such use.

Their review included results of the open-label GISSI Prevenzione study from 1999, which supported the initial authorization of these products, as well as retrospective cohort studies, more recent randomized controlled trials, and results of meta-analyses.

“The review concluded that, while a small relative risk reduction was seen in the original open label GISSI Prevenzione study, such beneficial effects were not confirmed in more recent randomized controlled trials,” the EMA said. The review found no new safety concerns.

The Committee’s decision does not affect the authorization of omega-3 fatty acid medicines for the treatment of hypertriglyceridemia.

The CHMP opinion will now be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU member states.

Support for the CHMP decision comes from results of the large VITAL trial, which found little benefit from omega-3 supplements (or vitamin D supplementation) for the prevention of cardiovascular disease, as reported by Medscape Medical News.

In the ASCEND trial, a 1 g dose of omega-3 fatty acids had no effect on serious vascular events (or cancer or mortality) when used for primary prevention in patients with diabetes.

However, in the REDUCE-IT trial, a high-dose purified form of the omega-3 oil, eicosapentaenoic acid (EPA), in patients with elevated triglycerides who had cardiovascular disease or diabetes and one additional risk factor did show significant benefit, with a 25% relative risk reduction in major adverse cardiovascular events.

Novartis receives positive CHMP opinion for Ilaris® in active Systemic Juvenile Idiopathic Arthritis, a serious form of childhood arthritis.



  • The CHMP has endorsed the use of Ilaris® in patients aged 2 years and older who suffer from Systemic Juvenile Idiopathic Arthritis (SJIA)
     
  • In Phase III studies, 84% of Ilaris-treated SJIA patients achieved significant improvement of systemic and arthritic symptoms (pediatric ACR30) after a single subcutaneous dose[1]
  • Ilaris is the first interleukin-1 beta inhibitor to receive such an opinion for the treatment of SJIA and, once approved, will be the only treatment that is given as a monthly subcutaneous injection.

 

Basel, July 26, 2013 – Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for the use of Ilaris® (canakinumab) in the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older. SJIA is a rare and disabling form of childhood arthritis with limited treatment options[2]. The condition is characterized by spiking fever, rash and arthritis that can affect children as young as 2 years old and can continue into adulthood[2],[3].

 

This opinion was based on two Phase III trials in SJIA patients, aged 2-19, which showed significant improvement in the majority of Ilaris-treated patients[1]. Study 1 showed that 84% of patients treated with one subcutaneous dose of Ilaris achieved the primary endpoint of the adapted pediatric American College of Rheumatology 30 (ACR30), compared to 10% achievement of ACR30 for placebo at Day 15[1]. In the open-label part of Study 2, 92 of 128 patients attempted “corticosteroid tapering”. Of those 92 patients, 62% were able to substantially reduce their use of corticosteroids, and 46% completely discontinued corticosteroids[1]. In the controlled portion of Study 2, there was a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group (hazard ratio of 0.36; 95% CI: 0.17 to 0.75)[1].

 

CHMP recommended Ilaris for the treatment of active SJIA in patients aged 2 years and older who have responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and systemic corticosteroids. CHMP stated that Ilaris can be given as monotherapy or in combination with methotrexate.

 

“If approved, Ilaris would provide a new treatment option for patients whose choice of therapy has, to date, been very limited,” said Timothy Wright, MD, Global Head of Development, Novartis Pharmaceuticals. “This positive opinion by the CHMP is an important step towards the approval of Ilaris for SJIA in the EU.”

 

The European Commission generally follows the recommendations of the CHMP and usually delivers its final decision within three months of the CHMP recommendation.

 

The incidence of SJIA in Europe is thought to be around 0.4-0.8 per 100 000[3], with a prevalence estimated at 1-10 in 30,000 children[4]. Although the disease can be life-threatening, treatment options are limited. Corticosteroids are often used to treat symptoms and pain despite their long term use being associated with potentially serious adverse effects, including Cushing syndrome, growth suppression and osteoporosis[1].

 

Ilaris is being investigated in a number of inflammatory diseases where interleukin-1 (IL-1) beta is a key component of disease pathogenesis. These include rare autoinflammatory conditions for which approved treatments do not exist, including, Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), colchicine-resistant Familial Mediterranean Fever (FMF) and Hyper IgD Syndrome (HIDS). Ilaris is considered an investigational agent for these conditions at this point in time. As such, the role that Ilaris could play in treating these conditions and potential benefit to patients is still being determined.

 

About the Pivotal Phase III Studies

Study 1, a 4-week, randomized, double-blind, placebo-controlled study, involved 84 patients between the ages of 2 and 19 years with active SJIA[1],[2]. Patients were treated with either a single subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) (n=43) or placebo (n=41)[1]. The primary endpoint was the proportion of patients achieving the adapted pediatric American College of Rheumatology (ACR) 30 response criteria and resolution of fever from baseline at Day 15[1]. This means that patients had at least a 30% improvement in systemic and arthritic symptoms versus baseline. The study met its primary endpoint.

 

Study 2, a two-part study, had an open-label, single-arm active treatment in Part I followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design in Part II[1]. A total of 177 patients between the ages of 2 and 19 years with active SJIA were enrolled in the study[1]. Some of these patients had previously participated in the Study 1. In Part I, patients received a subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) every 4 weeks[1]. The primary endpoint of Part I was to assess whether treatment with Ilaris allowed successful tapering of corticosteroids in at least 25% of SJIA patients who entered the study using a corticosteroid.

 

In Part II of the study, patients were randomized to either continue receiving Ilaris, or to receive placebo every 4 weeks (“placebo-after-Ilaris group”), until a pre-specified number (37) of flare-events (“flares”) had occurred[1]. The primary endpoint of Part II was to demonstrate that the time to flare was longer with Ilaris than with placebo.

 

The primary endpoints for Study 1 and Study 2 were all met.

 

About Ilaris

Ilaris is a selective, fully human, monoclonal antibody that inhibits IL-1 beta, which is an important part of the body’s immune system defenses[1]. Excessive production of IL-1 beta plays a prominent role in certain inflammatory diseases[5]. Ilaris works by neutralizing IL-1 beta for a sustained period of time, therefore inhibiting inflammation[1].

 

Ilaris is approved for the treatment of SJIA in the US and for the symptomatic treatment of refractory acute gouty arthritis in the EU. Ilaris is also approved in more than 60 countries, including in the EU, US, Switzerland and Japan for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a rare, lifelong, genetic disorder with debilitating symptoms. The approved indication may vary depending upon the individual country.

 

References:
[1] Ruperto N, Brunner H, Constantin T, et al. Baseline characteristics of patients with active Systemic JIA successfully discontinuing corticosteroid while receiving canakinumab: secondary analysis from a pivotal phase 3 trial. Abstract presented at European League Against Rheumatism, Madrid 12-15 June, 2013.
[2] Woo P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Pract Rheumatol 2006; 2(1):28-34.
[3] Ramanan AV, Grom AA. Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis? Rheumatology (Oxford) 2005; 44(11):1350-3.
[4] ORPHANET – http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=85414.Accessed 12th June 2013.
[5] Martinon F, Petrilli V. Gout-associated uric acid crystals activate the NALP3 inflammasome.Nature 2006; 440(9): 237-241.

 

Source: Novartis Newsletter

 

Novartis drug Votubia® recommended by CHMP for EU approval to treat patients with non-cancerous kidney tumors associated with TSC.


  • Votubia (everolimus) would be the first non-surgical treatment option in the EU for kidney tumors associated with tuberous sclerosis complex (TSC)[1]
  • Kidney tumors, or renal angiomyolipomas, affect up to 80% of patients with TSC and growing tumors may lead to life-threatening complications[2]

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Votubia® (everolimus) tablets* for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC) who are at risk of complications (based on factors such as tumor size or presence of aneurysm, or presence of multiple or bilateral tumors) but who do not require immediate surgery. Votubia would be the first medication available in the European Union (EU) for these patients[1].

“Today’s positive CHMP opinion for Votubia is important for patients in the EU with TSC, as renal angiomyolipoma is among the most difficult-to-treat manifestations of this debilitating disease,” said Hervé Hoppenot, President, Novartis Oncology. “There remain many unmet medical needs in TSC, and Novartis is committed to understanding and improving the lives of people affected by this rare disease through clinical research, education and collaboration with the global TSC community.”

In the EU, the European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 27 EU member states plus Iceland and Norway. In Europe, everolimus has orphan drug designation for TSC. Orphan drugs are those that treat a condition which affects no more than five in 10,000 people in the EU[3].

The CHMP positive opinion is based on data from the Phase III EXIST-2 (EXamining everolimus In a Study of TSC) trial, which found that 42% of patients on everolimus experienced an angiomyolipoma response versus 0% of patients in the placebo arm (p<0.0001). The evidence is based on analysis of change in sum of angiomyolipoma volume. Median time to angiomyolipoma progression was 11.4 months in the placebo arm and was not reached in the everolimus arm (p<0.0001). Among the 97% of patients with skin lesions, one of the key concerns for the majority of patients with TSC, a 26% response rate was seen with everolimus versus 0% with placebo (p=0.0002)[4].

Everolimus works by inhibiting mTOR, a protein implicated in many tumor-causing pathways[2],[5]. TSC is caused by defects in the TSC1 and/or TSC2 genes[2]. When these genes are defective, mTOR activity is increased, which can cause uncontrolled tumor cell growth and proliferation, blood vessel growth and altered cellular metabolism[5],[6]. According to preclinical studies, by inhibiting mTOR activity in this signaling pathway, everolimus reduces cell proliferation and blood vessel growth[1],[5].

About Renal Angiomyolipomas
Up to 80% of patients with TSC – a genetic disorder affecting approximately one to two million people worldwide that may cause non-cancerous tumors to form in many organs – will develop renal angiomyolipomas. Typical symptom onset occurs between the ages of 15 and 30 and prevalence increases with age. Over time, these tumors may grow large enough to cause severe internal bleeding, require emergency surgical interventions, such as embolization and nephrectomy, or lead to kidney failure[2]. The tumors can be difficult to manage as they are often multiple and form in both kidneys at the same time[1],[2]. In the EU, approximately 7,000 TSC patients have large growing AML tumors (> 3 cm) at risk of bleeding[7],[8],[9].

About EXIST-2
EXIST-2 is the first double-blind, randomized, placebo-controlled, international, multicenter Phase III study for the treatment of patients with renal angiomyolipoma associated with TSC. Trial patients (median age=31, range 18-61) were randomized 2:1 to receive either everolimus (n=79) or placebo (n=39) at a daily dose of 10 mg. The median duration of blinded study treatment was 48 weeks in the everolimus arm and 45 weeks in the placebo arm[4].

In the study, 42% of patients on everolimus (33 of 79; 95% confidence interval [CI] 30.8-53.4) experienced an angiomyolipoma response versus 0% on placebo (0 of 39; 95% CI 0.0-9.0; p<0.0001), defined as a 50% or greater reduction in the sum of angiomyolipoma volume relative to baseline, the absence of new tumor growth at least 1 cm in longest diameter, absence of kidney volume increase of 20% or greater and no renal angiomyolipoma-related bleeding of Grade 2 or higher[4].

Everolimus demonstrated superiority to placebo for both supportive efficacy outcomes measured: time to angiomyolipoma progression and skin lesion response rate. There were three patients in the everolimus arm and eight patients in the placebo arm with documented angiomyolipoma progression by central radiologic review. The time to angiomyolipoma progression was statistically significantly longer in patients on everolimus (hazard ratio [HR] 0.08, 95% CI 0.02-0.37; p<0.0001). Skin lesion response rate was significantly higher in the everolimus arm. A partial clinical response in skin lesions (corresponding to a 50% or greater improvement) was observed by Physician Global Assessment in 26% of patients on everolimus, compared with 0% of patients on placebo (p=0.0011). No complete responses were observed[4].

The most common adverse reactions reported in the everolimus arm during the double-blind period (with an incidence at least 15%) included stomatitis, hypercholesterolemia, aphthous stomatitis, mouth ulceration, and acne. The most common Grade 3 adverse reactions in the everolimus arm (with an incidence of at least 2%) were amenorrhea, aphthous stomatitis, and mouth ulceration. The most common laboratory abnormalities (incidence >= 50%) were hypercholesterolemia, hypertriglyceridemia and anemia. The most common Grade 3-4 laboratory abnormality (incidence >= 3%) was hypophosphatemia[4].

About everolimus
Everolimus is approved as Afinitor® (everolimus) tablets in the United States (US) for the treatment of adult patients with renal angiomyolipomas and tuberous sclerosis complex (TSC), not requiring immediate surgery. The effectiveness of Afinitor in treatment of renal angiomyolipoma is based on an analysis of durable objective responses in patients treated for a median of 8.3 months. Further follow-up of patients is required to determine long-term outcomes. Should everolimus be approved in the European Union (EU) for this patient population, the trade name will be Votubia.

Everolimus is also approved in the US as Afinitor and Afinitor Disperz(TM) in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. The effectiveness is based on demonstration of durable objective response, as evidenced by reduction in SEGA tumor volume. Improvement in disease-related symptoms and overall survival in patients with SEGA and TSC have not been demonstrated. In the EU, everolimus is approved as Votubia® (everolimus) tablets for the treatment of patients aged 3 years and older with SEGA associated with TSC who require therapeutic intervention but are not amenable to surgery. The evidence is based on analysis of change in SEGA volume. Further clinical benefit, such as improvement in disease-related symptoms, has not been demonstrated.

Everolimus is approved as Afinitor in 90 countries including the US and throughout the EU in the adult oncology settings of advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy in the EU and after failure of treatment with sunitinib or sorafenib in the US. Afinitor is approved for the treatment of locally advanced, metastatic or unresectable progressive neuroendocrine tumors of pancreatic origin in adults in the US and EU. Afinitor is also approved in the EU for the treatment of hormone receptor-positive (HR+), HER2/neu-negative (HER2-) advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor, and in the US for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ breast cancer) in combination with exemestane after failure of treatment with letrozole or anastrozole.

Everolimus is also available from Novartis for use in other non-oncology patient populations under the brand names Certican® and Zortress® and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country.

Important Safety Information about Votubia/Afinitor
Votubia/Afinitor can cause serious side effects including lung or breathing problems, infections, and renal failure which can lead to death. Mouth ulcers and mouth sores are common side effects. Votubia/Afinitor can affect blood cell counts, kidney and liver function, and blood sugar and cholesterol levels. Votubia/Afinitor may cause fetal harm in pregnant women. Highly effective contraception is recommended for women of child-bearing potential while receiving Afinitor and for up to 8 weeks after ending treatment. Women taking Votubia/Afinitor should not breast feed.

The most common adverse drug reactions (incidence >=15%) are mouth ulcers, diarrhea, feeling weak or tired, skin problems (such as rash or acne), infections, nausea, swelling of extremities or other parts of the body, loss of appetite, headache, inflammation of lung tissue, abnormal taste, nose bleeds, inflammation of the lining of the digestive system, weight decreased and vomiting. The most common Grade 3-4 adverse drug reactions (incidence >=2%) are mouth ulcers, feeling tired, low white blood cells (a type of blood cell that fights infection), diarrhea, infections, inflammation of lung tissue, diabetes and amenorrhea. Cases of hepatitis B reactivation and blood clot in the lung and leg have been reported.

*Known as Afinitor® (everolimus) tablets for this patient population in the US. If approved in the EU for this patient population, the trade name will be Votubia.

References

[1] Ewalt D, et al. Long-term outcome of transcatheter embolization of renal angiomyolipomas due to tuberous sclerosis complex. J Urol. 2005;174:1764-1766.
[2] National Institute of Neurological Disorders and Stroke. Tuberous Sclerosis Fact Sheet. Available at http://www.ninds.nih.gov/disorders/tuberous_sclerosis/detail_tuberous_sclerosis.htm. Accessed September 2012.
[3] European Medicines Agency. Orphan drugs and rare diseases at a glance. Available at http://www.ema.europa.eu/docs/en_GB/document_library/Other/2010/01/WC500069805.pdf. Accessed September 2012.
[4] Novartis Data on File.
[5] Motzer, et al. Phase 3 Trial of Everolimus for Metastatic Renal Cell Carcinoma. Cancer. 2010 Sep;116(18):4256-4265.
[6] Krueger D, et al. Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis. N Engl J Med. 2010 Nov;363(19):1801-11.
[7] Dixon B, et al. Tuberous Sclerosis Complex Renal Disease. Nephron Exp Nephrol. 2011:118:e15-e20.
[8] O’Callaghan F, et al. An epidemiological study of renal pathology in tuberous sclerosis complex. BJU International. 2004:94:853-857.
[9] Cox J, et al. The natural history of renal angiomyolipomata (AMLs) in Tuberous Sclerosis Complex (TSC). European Renal Association – European Dialysis and Transplant Association Congress. 2012, Paris, France.

Source: Novartis Newsletter.

Novartis announces two CHMP positive opinions for new indications of Galvus® and Eucreas® combined with other diabetes treatments .


  • Positive opinion for the use of vildagliptin, with or without metformin, in combination with a stable dose of insulin[1]
  • Additional positive opinion for the use of vildagliptin in combination with a sulphonylurea and metformin[1]
  • Positive opinions open the way for new treatment options for patients unable to reach their blood sugar goals

Novartis announced today that the European Medicines Agency‘s Committee for Medicinal Products for Human Use (CHMP) has issued two positive opinions for new indications for the use of Galvus® (vildagliptin) and Eucreas® (vildagliptin and metformin) in combination with other treatments for type 2 diabetes patients[1].

 

The first positive opinion was for vildagliptin in combination with insulin, with or without metformin, for patients with type 2 diabetes when diet, exercise and a stable dose of insulin do not result in glycemic control[1]. The second positive opinion was for vildagliptin in triple combination with metformin and a sulphonylurea for the treatment of type 2 diabetes when diet and exercise plus dual therapy with these two agents do not provide adequate glycemic control[1].

 

“These CHMP positive opinions are important milestones in our efforts to offer physicians and patients effective and generally well-tolerated additional treatment options to help reach and maintain blood sugar goals,” says David Morris, Primary Care Franchise Head of Development, Novartis Pharmaceuticals.

 

The CHMP positive opinion for the use of vildagliptin in combination with insulin was based on a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (n=449) which demonstrated that vildagliptin 50 mg administered twice daily in combination with insulin, with or without metformin, reduced blood sugar levels (HbA1c) versus placebo (-0.7%; P<0.001)[2]. The addition of vildagliptin was weight neutral and resulted in a similar incidence of hypoglycemia versus placebo[2].

 

The CHMP positive opinion for the use of vildagliptin in combination with metformin and a sulphonylurea was based on a 24-week, randomized, double-blind, placebo-controlled, parallel-group trial (n=318)[1]. The study demonstrated that vildagliptin 50 mg twice-daily in combination with metformin and a sulphonylurea reduced blood sugar levels (HbA1c) versus placebo (-0.8%; P<0.001)[1]. Five times as many patients reached their blood sugar level goal versus placebo (28.3% for vildagliptin versus 5.6% for placebo; P<0.001)[1]. The addition of vildagliptin was weight neutral versus placebo and had a low incidence of hypoglycemia[1]. As part of the positive opinion, it was noted that sulphonylureas are known to cause hypoglycemia so physicians may consider a lower dose of sulphonylurea to reduce this risk when combining treatments[1].

 

Upon approval, vildagliptin in combination with insulin, with or without metformin, and vildagliptin in combination with metformin and a sulphonylurea will offer new treatment options for patients unable to reach blood sugar goals, with a low risk of hypoglycemia while also achieving weight neutrality[1],[3].

 

About diabetes

Diabetes is one of the world’s greatest healthcare challenges, affecting 366 million people globally and killing one person every seven seconds[4]. The obesity epidemic and an aging world population are contributing to the escalating incidence of type 2 diabetes and by 2030 it is projected that more than half a billion people will be diagnosed with the disease[4]. Type 2 diabetes accounts for 90 percent of all cases of the disease[5].

 

About Galvus®

Galvus® (vildagliptin) is a dipeptidyl peptidase-4 (DPP-4) inhibitor, a class of oral diabetes medications that enhance the body’s natural ability to control blood sugar. The Galvus® (vildagliptin) safety and efficacy profile has been established in a comprehensive clinical trial program that included more than 15,000 type 2 diabetes patients[6].

 

Galvus® (vildagliptin) is approved in more than 100 countries across Europe, Asia Pacific, Africa and Latin America. It is indicated for the treatment of type 2 diabetes as a monotherapy and in combination with metformin, a sulphonylurea, a thiazolidinedione or insulin[6]. Specific indications vary by country.

 

About Eucreas/Galvus® Met

Eucreas®/Galvus® Met (vildagliptin and metformin) is a single-pill fixed-dose combination of Galvus® (vildagliptin) and metformin. Eucreas®/Galvus® Met (vildagliptin and metformin) is approved in more than 80 countries across Europe, Asia Pacific, Africa and Latin America for the treatment of patients with type 2 diabetes who are unable to control blood sugar with metformin alone[7]. Specific indications vary by country.

 

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as “positive opinion,” “open the way,” “milestones,” “will,” “projected,” or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Novartis vildagliptin products or regarding potential future revenues from such products. 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 Novartis vildagliptin products to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Novartis vildagliptin products will be approved for any additional indications or labeling in any market. Nor can there be any guarantee that such products will achieve any particular levels of revenue in the future. In particular, management’s expectations regarding Novartis vildagliptin products 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; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; unexpected manufacturing issues; 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.

 

References

 

[1] Novartis Pharma AG data on file.

[2] Lukashevich V et al. Vildagliptin combined with insulin reduces HbA1c without increasing risk of hypoglycemia and weight gain in patients with type 2 diabetes mellitus. Poster presented at the 72nd American Diabetes Association; June 8-12, 2012; Philadelphia, PA, USA. Poster # 995-P.

[3] Inzucchi SE et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2012;55:1577-1596.

[4] International Diabetes Federation. Global diabetes plan. http://www.idf.org/sites/default/files/Global_Diabetes_Plan_Final.pdfAccessed September 7, 2012.

[5] International Diabetes Federation. Types of diabetes. http://www.idf.org/types-diabetesAccessed September 7, 2012.

[6] Galvus Summary of Product Characteristics (SmPC).

[7] Eucreas Summary of Product Characteristics (SmPC).

 

Source: Novartis Newsletter.