Study Shows Neoral(R) Provides Kidney Transplant Patients With Efficacy Equivalent to Tacrolimus and Significantly Lower Incidence of Diabetes

BASEL, Switzerland, July 24 /PRNewswire-FirstCall/ -- A large-scale head- to-head study has shown that Neoral(R) (cyclosporine) and tacrolimus have equivalent efficacy in preventing organ rejection in kidney transplant patients, but those treated with Neoral had a significantly lower incidence of new-onset diabetes.

Diabetes is a major risk factor for cardiovascular death in transplant patients. The study results suggest that immunosuppressant efficacy is not the only factor to affect the long-term outcome for patients surviving organ transplantation. The findings of the study were presented today at the World Transplant Congress in Boston.

"The results of this study are especially important in view of the clear association between diabetes and the development of cardiovascular disease, which is the leading cause of death in post-transplant patients with a functioning graft," said Flavio G. Vincenti, MD, a kidney and pancreas transplant specialist with the Department of Medicine at the University of California at San Francisco. "By demonstrating the equivalence of Neoral and tacrolimus in preventing organ rejection, this study elevates the need to address diabetes risk as a new strategy to prolong life in transplant patients."

The study, called DIRECT, is one of the largest ever conducted in transplant patients and gives new insight into the incidence of new-onset diabetes following transplantation. Diabetes post-transplantation is associated with a three-fold increase in the risk of ischemic heart disease and related mortality(2).

About the DIRECT trial

DIRECT (Diabetes Incidence after Renal transplantation: NEoral C-2 monitoring versus Tacrolimus) was a randomized, six-month, open label, international multi-center trial in which 682 patients who received kidney transplants were treated with either Neoral or tacrolimus to prevent organ rejection. At six months post-transplant, the study found no difference between Neoral and tacrolimus in the composite primary efficacy endpoint, including biopsy-proven acute rejections, graft loss or death.

However, there was a significantly lower incidence of new-onset diabetes or impaired fasting glucose in the Neoral group than the tacrolimus group (26% vs. 33.6%, [p=0.046]). The study results indicate significantly more tacrolimus patients required diabetes treatment than Neoral patients (18% vs. 12.5%, [p<0.05]).

"New onset diabetes after transplantation is an under-recognized and serious complication that needs to be effectively controlled from the outset," said Giacomo di Nepi, Global Head of Infectious Diseases, Transplant and Immunology at Novartis Pharma AG. "The findings of the DIRECT study suggest that clinicians need to consider carefully the selection of immunosuppressive agents based not only on efficacy, but also on the risk reduction of post- transplant diabetes."

International consensus guidelines on treating post-transplant diabetes highlight the choice of calcineurin inhibitors, such as Neoral and tacrolimus, as a modifiable risk factor that should be managed by clinicians based on each patient's diabetes and cardiovascular risk profile(3).

About Neoral

Neoral is a microemulsion formulation of the calcineurin inhibitor cyclosporine, which prevents rejection in organ transplant patients by selectively blocking specific immune cell activation at an early stage. Cyclosporine has the longest record in patient and organ survival of any immunosuppressant. Neoral is commonly used in combination with other agents and remains a cornerstone of immunosuppressive regimens.

Neoral is approved for the prevention of organ rejection following kidney, liver, heart, lung, combined heart-lung, pancreas and bonemarrow transplantation. It is also indicated for the prophylaxis of graft-versus- host disease (GVHD) following bonemarrow transplantation.*

Launched in 1995, Neoral is one the world's most widely prescribed immunosuppressants for organ transplant patients. More than 200,000 people worldwide currently protect their transplanted organs with Neoral or Sandimmun(R).

Disclaimer

The foregoing release contains forward-looking statements which can be identified by the use of terminology such as "strategy", or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Neoral, potential future revenue from Neoral, or regarding the long-term impact of a patient's use of Neoral. Such forward- looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Neoral to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Novartis will apply for, or be granted any new indications or labeling for Neoral, or that Neoral, which faces generic competition, will achieve any particular level of revenue. Neither can there be any guarantee regarding the long-term impact of a patient's use of Neoral. In particular, management's expectations regarding Neoral could be affected by, among other things, unexpected clinical trial results, including new clinical data and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; increased government, industry, and general public pricing pressures; and other risks and factors referred to in the Company's current Form 20-F on file with the U.S. 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 this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

About Novartis

Novartis has been a leader in the transplant area for more than 20 years, having pioneered early breakthrough treatments for organ protection with Neoral/Sandimmun. Novartis markets the broadest immunosuppressant portfolio in the industry with 4 products (Neoral(R) myfortic(R), Certican(R) and Simulect(R)) and continues to be active in the research and development of new compounds. The company's goal is to build an innovative range of therapeutic products for the prevention of organ rejection, in order to provide an extensive choice of drugs to the transplant community.

Novartis AG is a world leader in offering medicines to protect health, treat disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. Novartis is the only company with leadership positions in both patented and generic pharmaceuticals. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. In 2005, the Group's businesses achieved net sales of USD 32.2 billion and net income of USD 6.1 billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 96,000 people and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com/.

References (1) Lindholm A et al. Transplantation 1995; 60: 451-457/Howard RJ et al. Transplantation 2002; 73:1923-1928 (2) Kasiske BL et a. J Am Soc Nephrol 2000; 11:1735-1743 (3) Wilkinson A, et al. Guidelines for the treatment and management of new-onset diabetes after transplantation. Clin Transplant. 2005; 19:291-8. * Indications vary in different markets. Media contacts John Gilardi Novartis Global Media Relations +41 61 324 3018 +41 61 324 2200 john.gilardi@novartis.com Birgit Gronkowski Novartis Pharma Communications +41 61 324 8790 +41 79 820 1719 birgit.gronkowsi@novartis.com