Basel, 3 June 2003 - Lescol® (fluvastatin sodium) significantly reduces the combined incidence of cardiac death or non-fatal myocardial infarction (MI) in renal transplant patients compared to placebo, according to results of the Assessment of Lescol in Renal Transplantation (ALERT) study published today in the online version of The Lancet and being presented today at the American Transplant Congress, the joint annual meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.
ALERT is a unique trial, representing the largest prospective study in renal transplant recipients and the first to study cardiac and renal outcomes in this population. The primary endpoint was defined as the occurrence of major adverse cardiac events (MACE), consisting of cardiac death, non-fatal MI or coronary intervention. Although not statistically significant, fluvastatin demonstrated a positive trend versus placebo on the primary endpoint of MACE. However importantly, the risk of cardiac death and non-fatal MI was significantly reduced in fluvastatin-treated patients compared to placebo. Cardiovascular disease accounts for up to 70% of deaths in patients with successful kidney transplants.
"The results of the ALERT study confirm the benefits of Lescol in the prevention of cardiac events in a challenging, high-risk patient population," said Joerg Reinhardt, Ph.D., Head of Pharma Development, Novartis Pharma AG. "It also confirms the proven safety of this statin medication, even in renal transplant patients, who are not only at high risk for a cardiovascular disease but also have an increased risk of drug interactions."
ALERT was a multicenter, placebo-controlled study, enrolling 2,102 patients from nine countries, examining the effect of Lescol 40-80 mg daily versus placebo in renal transplant recipients receiving immunosuppressive therapy with cyclosporin who had mild to moderate elevated LDL cholesterol levels. Follow-up extended for five to six years.
Key Findings
Treatment with Lescol demonstrated a favorable trend towards reduction in the risk of MACE, the primary endpoint for this trial, although the difference compared to placebo was not statistically significant (p=0.139). On the hard cardiovascular endpoints, treatment with Lescol (40-80 mg daily) demonstrated a significant 38% reduction in the risk of cardiac death (p=0.031), a 32% reduction in the risk of non-fatal MI (p=0.050) and a 35% reduction in the cumulative incidence of cardiac death or first non-fatal MI (p=0.005).
Fluvastatin significantly reduced low-density lipoprotein cholesterol (LDL) by 32% compared with placebo and brought most patients to LDL target based on US and European guidelines for heart disease prevention. ALERT also found that treatment with fluvastatin lowered triglyceride levels compared with placebo. Levels of high-density lipoprotein (HDL) cholesterol were significantly increased by 7 to 13% during the first four years of the study although the difference compared to the placebo group became negligible at study end for certain factors, which are currently being investigated.
In ALERT, no differences were seen in adverse event rates between the two groups. Similar incidences of critical elevations of alanine aminotransferase (ALT) or creatine kinase (CK) levels occurred in the Lescol- and placebo-treated populations. These data underscore the excellent safety profile of Lescol and are consistent with pooled analyses from previous clinical trials with Lescol and Lescol XL, which found that the rates of CK elevation with Lescol, alone or in combination with fibrates, were similar to placebo.
About Lescol/Lescol XL
Lescol and Lescol XL are statin drugs used in the treatment of cholesterol, atherosclerosis and vascular disease. Novartis introduced Lescol extended-release, once-daily 80 mg formulation in 2000 (Lescol XL), which has been shown in trials to provide effective lipid management, with reductions in harmful LDL-cholesterol of 38%, in triglycerides of 31% and increases in favourable HDL-cholesterol of up to 21%. Ballantyne et al. Efficacy and tolerability of fluvastatin extended-release deliver system: a pooled analysis. Clin Ther 2001;23:177-192.
This press release contains forward-looking statements relating to the business of Novartis, which can be identified by express or implied discussions regarding potential new indications or future sales for Lescol or Lescol XL. Such forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause actual results to be materially different from any future results, performance, or achievements expressed or implied by such statements. There can be no guarantees that the aforementioned clinical trial will result in any new indications for Lescol or Lescol XL in any market. Nor can there be any guarantees regarding any future sales of Lescol or Lescol XL. Many factors could cause the actual results, performance or achievements of the Company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. These factors include, among other things, uncertainties relating to clinical trials and product development, regulatory actions or delays or government regulation generally, the ability to obtain or maintain patent or other proprietary intellectual property protection, and competition in general, increased government pricing pressures, as well as factors discussed in the Company's Form 20F filed with the 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 described herein as anticipated, believed, estimated, or expected.
Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2002, the Group's businesses achieved sales of USD 20.9 billion and a net income of USD 4.7 billion. The Group invested approximately USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 77 200 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
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