Читать книгу Successful Drug Discovery, Volume 5 - Группа авторов - Страница 14

One contribution ideally suited for academic research is the quest for new indications.

As approved drugs are openly commercially available, researchers, particularly scientists in clinical centers, can – based on patient derived data – generate hypotheses and probe them in a straightforward manner. In this context drug repurposing has attracted a lot of attention as the approach is very straightforward, and the resulting drug has already been demonstrated to be safe, bioavailable, and well tolerated in humans.

Often, this approach is guided by careful observation of disease‐accompanying factors and interpretation of the underlying pathology. In particular, changes of symptoms in patients suffering from more than one disease may provide interesting starting points for developing new hypotheses. An example is rituximab, which first was developed for the treatment of cancer. Its discovery will be discussed in more detail during the course of the chapter. Edwards et al. proposed that self‐perpetuating B‐lymphocytes may play a key role in driving progression of rheumatoid arthritis (RA) and autoimmune diseases [6]. They hypothesized that a CD20 (cluster of differentiation 20) targeted therapeutic, capable of specifically depleting this population of B‐cells, may represent an interesting therapeutic option. In 1999, a first case report of a patient suffering from non‐Hodgkin's lymphoma in association with inflammatory arthropathy appeared [7]. Within weeks of treatment with a monoclonal anti‐CD20 antibody, significant improvement of joint pain was observed, and three months later, the patient was virtually symptom‐free and capable of walking distances of 5 miles per day. In a following phase 2 study, positive results of rituximab in patients with RA were demonstrated, [8] followed by further trials. After being able to demonstrate convincing beneficial effects, rituximab was approved for treatment of RA in combination with methotrexate in 2006.