29th Annual Meeting of the American Society of Photobiology

Downtown Marriot

Chicago, Il.

From the Chem Lab to the Patient. Drug Development at Roswell Park Cancer Institute.

Abstract-
Following development of Photofrin at Roswell Park Cancer Institute and subsequent commercialization by pharmaceutical companies, emphasis here has been on development of photosensitizers with improved photophysical and pharmacological properties, especially activation at longer wavelengths to improve depth of treatment, and lack of long-term cutaneous photosensitivity. Our approach has been to select a particular chromophore for the former (e.g. chlorin or bacteriochlorin types) and then to optimize the in vivo activity via structure-activity studies. Once a candidate photosensitizer has been identified, in-depth studies of pharmacokinetic characteristics and certain basic mechanistic studies are carried out. Assuming favorable outcome, a toxicological study is carried out in RPCI's FDA-approved toxicology lab. Before initiating these studies, an acceptable formulation (usually injectable) must be identified. When all the steps undertaken have produced promising results, an IND for FDA approval of a Phase I clinical trial is initiated. This extensive document contains all known information about the drug, including every piece of toxicology data, all papers relating to the drug, chemistry, stability, quality control, and the protocol for the proposed clinical trial. The FDA responds with reviews by various groups (chemistry, toxicology, medical) and after some back and forth, they may give permission to proceed. Once the clinical study begins, stringent controls regarding drug manufacture, formulation, sterility, pyrogenicity and patient forms are required and produce a 'paper trail' so that all aspects from the lab to the patient and thereafter can be reconstructed if necessary. The clinical trials are very expensive. In our experience, the institute has been willing to cover these costs with hopes that it will eventually be possible to find a commercial sponsor. So far this has been the case for our photosensitizers. These steps will be illustrated with a new photosensitizer from RPCI recently licensed for commercial development by a U. S. company.

Keywords: drug development, new photosensitizers