PARI Granted Orphan Drug Designation for Inhaled Cyclosporine - Potential for a New Treatment of Rejection Reactions Following Lung Transplants

STARNBERG, Germany

For over twenty years, lung transplants have been a commonly accepted treatment method throughout the world for patients with serious, incurable lung diseases. Until now however, acute and chronic rejection reactions to the implanted organ have lowered the patients�' chances of survival: only 45 percent of patients survive for longer than five years.

Researchers and developers at PARI GmbH - specialists for effective inhalation - consider the administration of inhaled Cyclosporine to be much superior to conventional treatments used in the prevention and treatment of rejection reactions following lung transplants. On June 16, 2004, the European licensing authority granted PARI ODD (Orphan Drug Designation) status for the inhaled Cyclosporine therapy hereby giving PARI the economic advantage of having market exclusivity for Cyclosporine for a period of 10-years. The licensing authority helps promote the discovery, development and marketing of medications for rare diseases.

Cyclosporine, a calcineurine immunosuppressor, is a medication used frequently following transplant operations for the suppression of the body�'s natural rejection of a foreign organ. PARI scientists are now preparing clinical studies to determine the necessary dosage of an innovative aqueous Cyclosporine formulation when administered with the new, highly efficient PARI-eFlowŽ membrane nebulizer. In clinical trials, an American group of researchers has already determined that inhaled Cyclosporine therapy has advantages over the conventional orally administered therapy because the drug reaches the critical area, the transplanted lung, directly.

Based on results from research with artificial lung models, the PARI scientists expect that, when administered with the eFlowŽ, the desired therapeutic effect can be achieved with significantly lower doses of inhaled Cyclosporine compared to oral therapies while simultaneously minimizing side effects. This should significantly improve the patients�' chances of survival and quality of life.

The current therapy with orally administered Cyclosporine requires high doses of medication in order to produce the desired concentration in the lung, as the active ingredient is distributed in the entire body. This causes a great number of dosis-dependent side effects, notably kidney and brain damage as well as an increased vulnerability to infections. Due to the poor solubility of Cyclosporine in water, the biological availability of the active ingredient and consequently the concentration of Cyclosporine in the lungs vary from patient to patient.

The oscillating, perforated membrane of the new electronic PARI-eFlowŽ nebulizer supports an efficient way of atomizing liquid medications. Compared with other nebulizers, eFlowŽ is able to deliver aerosols with a predefined droplet size and a high proportion of active ingredient reaching the lungs within the shortest possible time. Soundless operation, small dimensions, low weight, as well as the possibility of battery operation, make this device extremely user-friendly.

"Receiving ODD status for inhaled Cyclosporine by the European licensing authority confirms the fact that the Pharma business unit constitutes an important element in the PARI company structure and improves the company�'s prospects for the future. The Pharma drug development and testing expertise enables PARI to expand its original inhalation device business to include inhalable medication and thus become a system provider. In this way we are able to develop customized products for nasal and pulmonary applications that improve drug therapy and the quality of life of our patients," states Dr. Manfred Keller, Director of the PARI Business Unit Pharma. "In collaboration with transplant centers we will design a clinical development program for the Cyclosporine project so we can begin the necessary pharmacokinetic and clinical studies as soon as possible."

Orphan drugs are medications for the treatment of rare diseases. In Europe, the licensing authority for the development of such medications has been granting orphan drug status for selected medications since December 1999 providing incentives to pharmaceutical companies through shortened approval times and market exclusivity for a period of ten years. This promotes the research, development and launching of drugs for the treatment of rare diseases. In the USA, such incentives exist since 1983, in Japan since 1993.

Dr. Johannes-Christoph Stein

Steinerstrasse 15k

D-81369 Munich, Germany

Tel. +49-89-74-28-46-69

Fax +49-89-74-28-46-50

e-mail:j_stein@pari.de