Novartis Pharmaceuticals Corporation Files New Drug Application for Certican -everolimus- for the Prevention of Rejection Following Heart and Kidney Transplantation.

Business Editors/Health/Medical Writers

EAST HANOVER, N.J.--(BUSINESS WIRE)--Dec. 20, 2002--(NYSE: NVS)

Novartis Pharmaceuticals Corporation announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Certican(TM) (everolimus).

Novartis seeks to have Certican approved for the prevention of rejection episodes following heart and kidney transplantation.

The Certican NDA reports on the results of one of the most extensive drug development programs conducted to date for a transplantation product. Results from clinical studies that have followed more than 1,500 heart and kidney transplant recipients for up to 36 months showed that Certican, when administered concurrently with Neoral(R) (cyclosporine USP) MODIFIED and corticosteroids, effectively prevented graft rejection.

"Certican is the latest drug in a long and impressive line of products that Novartis has developed that have enhanced the lives of transplant recipients," said Jim Harold, Vice President Transplant and Immunology Business Unit, Novartis Pharmaceuticals Corporation. "It will be a welcome addition to our established portfolio of marketed products offering patients and physicians a greater choice of immunosuppressive therapies."

Heart Transplantation

Data from a two year phase III, international multi-center study comprised of a one year double-blind, randomized trial followed by a one year open label extension, demonstrated the efficacy and safety of 2 doses of Certican tablets (1.5 and 3 mg/day) compared with azathioprine (1-3 mg/kg/day) as part of triple immunosuppressive therapy in de novo adult heart recipients. At six and 12 months after transplant, Certican at both 1.5mg/day and 3mg/day was statistically superior to azathioprine with respect to the primary composite end-point, which includes the incidence of acute rejection greater than ISHLT grade 3A, acute rejection associated with hemodynamic compromise, graft loss, patient death and loss to follow-up.

The incidence of biopsy-proven acute rejection greater than or equal to ISHLT grade 3A at month 12 was 30.6% for the 1.5 mg/day group, 21.3% for the 3 mg/day group and 45.8 percent for the azathioprine group.

Based on coronary artery ultrasound data (intravascular ultrasound), compared to the azathioprine group, both Certican doses were associated with a significantly lower incidence of allograft vasculopathy (a narrowing of the coronary artery supplying blood to the heart; a cause of late graft loss).

Kidney Transplantation

Two phase III, international multi-center, double-blind, randomized, parallel group studies (B201, B251) were designed to assess the effect of two doses of Certican (1.5 and 3 mg/day) compared with mycophenolate mofetil (2g/day) as part of a triple immunosuppressive therapy regimen with Neoral and corticosteroids. The studies demonstrated that Certican was generally safe and well tolerated. With respect to the primary composite end-points (biopsy-proven acute rejection, graft loss, death or loss to follow-up) there were no significant between-group differences observed for efficacy at six or 12 months post-transplant.

In the first study, B201, the incidence of biopsy-proven acute rejection at 12 months was 23.2%, 19.7% and 24.0% for the Certican 1.5mg/day, Certican 3mg/day and mycophenolate mofetil groups respectively. In the second study, B251, the incidence of biopsy-proven acute rejection was 19.2%, 22.2% and 24.0% for the Certican 1.5mg/day, Certican 3mg/day and mycophenolate mofetil groups respectively.

Certican is a potent proliferation inhibitor with immunosuppressant properties that targets primary causes of rejection. The Marketing Authorization Application for Certican was submitted in the European Union (EU) in July 2002.

Certican is contraindicated in patients with known hypersensitivity to everolimus or its derivatives or to components of the drug product. On average, heart and renal recipients treated with Certican, full-dose cyclosporine and corticosteroids exhibited lower renal clearance of creatinine than patients receiving MMF or azathioprine respectively. Reduction in cyclosporine doses resulted in stabilization or improvement of renal function in most patients. Additionally, data from a phase II kidney study showed that Certican with reduced dose cyclosporine maintained efficacy with improved renal function compared to Certican plus full dose cyclosporine.

Patients receiving immunosuppressive drugs (including Certican) are at increased risk of infections and developing lymphomas or other malignancies, particularly of the skin, and should be monitored carefully. The most frequently reported adverse events include hypertension, elevated lipids, gastrointestinal disturbances and decreased red blood cell count.

Additional Information

For more than 20 years, Novartis has been a committed partner to the transplant community providing vital support to increase organ donation, educate patients and clinicians and assist those unable to afford therapy. As a leading contributor to the advancement of transplant science and medicine, Novartis has created a broad pipeline in the field of transplantation, with three compounds in clinical trials and additional products in pre-clinical development. The focus of this extensive research and development effort is to expand available therapeutic options for transplant patients, to improve their quality of life and to enhance the long-term success of transplant therapy.

Neoral is indicated for the prophylaxis of organ rejection in kidney, liver and heart allogeneic transplants, severe rheumatoid arthritis and severe recalcitrant psoriasis. Only physicians experienced in management of systemic immunosuppressive therapy for the indicated disease should prescribe Neoral. In transplant recipients, the principal side effects of Neoral include renal dysfunction, tremor, hypertension, gum hyperplasia and hirsutism. Neoral is contraindicated in patients with hypersensitivity to cyclosporine or to any ingredients in the formulation. Rheumatoid arthritis and psoriasis patients with abnormal renal function, uncontrolled hypertension or malignancies should not receive Neoral.

Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions in a variety of therapeutic areas including pulmonology, rheumatology, central nervous system medicine, organ transplantation, cardiology, dermatology, gastroenterology, and oncology. The company's mission is to improve people's lives by pioneering novel healthcare solutions.

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS), a world leader in healthcare with core businesses in pharmaceuticals, consumer health, generics, eye-care, and animal health. In 2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1 billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D.

Headquartered in Basel, Switzerland, Novartis Group companies employ about 72,600 people and operate in over 140 countries around the world. For further information please consult http://www.pharma.us.novartis.com/ or http://www.novartis.com.

The foregoing press release contains forward-looking statements which can be identified by terminology such as "will be", "novel", "expand available therapeutic options ", "impressive", "enhanced", "superior", "potent", "extensive" or similar expressions, or by express or implied discussions regarding the potential approval of the New Drug Application described above, or potential additional revenue to Novartis from Certican sales. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results to be materially different from any future results, performance, or achievements expressed or implied by such statements. There are no guarantees that the aforementioned New Drug Application will result in an approval to market Certican, or in any additional revenue to Novartis from Certican sales. Any such results can be affected by, amongst other things, unexpected regulatory actions or government regulation generally, the introduction and performance of competitive products for the same or similar indications, government pricing policies, the company's ability to obtain or maintain patent and other proprietary intellectual property protection, and competition in general, as well as factors discussed in Novartis AG's Form 20-F filed with the Securities and Exchange Commission. Any of these and other factors can cause the actual results to differ materially from the expected or predicted results.