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Vildagliptin Study Demonstrates Equivalent Efficacy to Rosiglitazone in Phase 3 Trial

Basel, September 14, 2006 - Galvus (vildagliptin), submitted for US and EU approval as a once-daily oral treatment for type 2 diabetes, has demonstrated impressive efficacy and an attractive tolerability profile that may benefit many people currently struggling to control their disease.

These findings from Phase III studies were presented at the 42nd European Association for the Study of Diabetes (EASD) meeting in Copenhagen, Denmark.

Galvus showed equivalent efficacy to the diabetes medicine rosiglitazone, an insulin sensitizer known as a thiazolidinedione (or TZD), in a head-to-head monotherapy study that led to an overall 1.8% reduction in blood sugar levels as measured by HbA1c (A1c). The results were achieved without weight gain overall and with a lower incidence of edema (fluid retention) - both of which are side effects commonly associated with TZDs[1].

"Patients and physicians need additional therapies that address the primary cause of diabetes, which is pancreatic islet dysfunction," said Professor Emanuele Bosi, Director of the Diabetes & Endocrinology Unit at San Raffaele University Hospital in Milan, Italy.

"Vildagliptin has been tested in combination with many currently available drugs, resulting in effective A1c reductions with an excellent side-effect profile. Many patients and physicians have come to unfortunately regard the side effects of current therapies as normal and accept them as part of their treatment. These results are very reassuring for patients who have to take medications to treat their diabetes for a long time," said Professor Bosi.

Even among people receiving diabetes care, controlling blood sugar levels is difficult. More than half of those currently taking medicines for diabetes are still not reaching their blood sugar targets, according to the National Health and Nutrition Examination Survey (NHANES)[2]. Diabetes is a progressive disease where blood sugar control deteriorates over time, failure to properly control diabetes can lead to heart and kidney disease, blindness, vascular and neurological problems[3],[4].

Type 2 diabetes currently affects about 230 million people worldwide and is expected to grow to more than 350 million by 2025, according to the International Diabetes Federation. While the disease burden among Western nations is great, the IDF projects a 170% increase in type 2 diabetes cases in the developing world by 2025[4].

Galvus, a member of the DPP-4 inhibitor class, works through a novel mechanism of action targeting the pancreatic islet dysfunction that causes high blood sugar levels in people with type 2 diabetes. Islet dysfunction can specifically lead to excess sugar production (via glucagon from the alpha-cells) and reduced insulin production (from the beta-cells). Galvus affects both pancreatic alpha- and beta-cells, improving their ability to appropriately sense and respond to sugar in the blood.

The European marketing application for Galvus was filed in August 2006, while the US submission was completed in March 2006. The submissions included data from clinical trials involving more than 5,400 patients worldwide.

Trial data at EASD underscore effective once-daily treatment The four highlighted trials at EASD were part of a broad overview of clinical data summarizing the development as well as overall efficacy and tolerability of Galvus. A total of 17 clinical and preclinical Galvus investigations were part of the congress scientific program.

"Clinical trials have consistently shown that Galvus provides significant efficacy with good tolerability in a variety of patients," said James Shannon, MD, Global Head of Development at Novartis Pharma AG. "We are extremely excited that the Galvus profile could change the management of type 2 diabetes for many millions of people around the world."

The head-to-head monotherapy comparison of Galvus (100 mg daily) and rosiglitazone (8 mg daily) involved 697 patients in a six-month study. Galvus reduced blood sugar levels significantly as measured by A1c and was comparable to the TZD, particularly in high baseline patients (-1.8%). Galvus treatment was not associated with weight gain overall, while people in the rosiglitazone group gained on average 1.6 kg. Galvus-treated patients also experienced a lower incidence of edema (2.5% vs. 4.9%)[1]. (EASD abstract #0789)

In another study presented at EASD, a treatment combination of Galvus and the TZD pioglitazone resulted in 65% of patients on Galvus achieving the American Diabetes Association (ADA)-defined A1c blood sugar goal of less than 7% compared to 42% of those who achieved this goal on monotherapy treatment (Galvus 42.5% or pioglitazone 42.9%). Side effects were consistent with the individual tolerability profiles of Galvus and TZDs, while the combination was also well tolerated[5]. (EASD abstract #0801)

A new dose-ranging study presented at EASD concluded that Galvus taken once-daily was effective in lowering A1c levels. The trial of 279 patients who had not been treated previously with diabetes medicines found similar, significant A1c reductions among patients taking Galvus 100 mg daily, regardless of whether this was given as a once-daily dose or as 50 mg twice-daily[6]. (EASD abstract #0791)

Another presentation showed positive results of a 24-week trial when Galvus was combined with metformin, another commonly prescribed diabetes medicine. The results showed a 1.1% reduction in blood sugar level as measured by A1c when compared to metformin alone[7]. Galvus was also very well tolerated in this study[7]. (EASD abstract #0793)

Throughout the clinical development program, Galvus has shown no weight gain overall. In one study, obese patients treated with Galvus demonstrated a relative weight benefit of 2.8 kg compared to those taking TZDs[3]. This is potentially important since many people with type 2 diabetes often struggle to keep their weight under control.

Galvus has also demonstrated a good tolerability profile with a very low incidence of hypoglycemia (excessively low blood sugar) and edema (fluid retention) in monotherapy trials. The most commonly seen side effects in clinical studies with Galvus include cold/flu like symptoms, headache and dizziness[3].

References
1. Schweizer, S. Dejager, M.A. Baron, D. Mills, Y. Amiour, J. Rosenstock. Vildagliptin is as Effective as Rosiglitazone in Drug-Naïve Patients with Type 2 Diabetes and Does Not Cause Weight Gain. Presented at EASD September 14, 2006

2. S.H. Saydah, J. Fradkin, C.C. Cowie. Poor Control of Risk Factors for Vascular Disease Among Adults with Previously Diagnosed Diabetes. JAMA 2004; 291(3):335 342.

3. Data on file, Novartis Pharma AG

4. http://www.idf.org/home/index.cfm?node=37 , accessed March 9, 2006

5. J. Rosenstock, M.A. Baron, B. Bassiri, E. Rochotte, F. Cressier, Y. Amiour, C. Hsu, R.-P. Camisasca, S. Dejager, A. LeBeaut. Efficacy of Vildagliptin Combined with Pioglitazone in Patients with Type 2 Diabetes. Presented at EASD September 14, 2006

6. S. Dejager, M.A. Baron, S. Razac, J.E. Foley, S. Dickinson, A. Schweizer. Efficacy of Vildagliptin in Drug-naïve Patients with Type 2 Diabetes. Presented at EASD September 14, 2006

7. E. Bosi, C. Collober, E. Rochotte, R.-P. Camisasca, A.J. Garber. Vildagliptin added to Metformin Improves Glycaemic Control by Decreasing Fasting and Postprandial Glucose in Patients with Type 2 Diabetes. Presented at EASD September 14, 2006

Source: Novartis

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