Is a new treatment in development (SB-656933) for the treatment of CF safe?
Why is this important?
Cystic fibrosis is characterized by infection and inflammation in the airways. Inflammation occurs in response to infection and causes lung damage. Reducing inflammation in the lungs, with the aim to reduce damage, is a major unmet need for people with CF. Reducing inflammation though must be achieved without worsening infection. Neutrophils are the major infection-fighting white blood cells that cause lung inflammation in CF. In laboratory studies, the GlaxoSmithKline investigational medicine reduces the activity of neutrophils without dampening their anti-infective abilities.
What did you do?
In order to examine for the first time if SB-656933 is safe in people with CF, we tested the safety and early markers of efficacy of this oral medicine at two doses compared to placebo in a randomized double-blind controlled one month clinical trial of 146 adults with CF at 31 centres in the United States, France, Germany and Israel.
What did you find?
The study investigated the safety of SB-656933 and there was no evidence of worsening infection or other increased side effects compared to placebo. Lung function and other clinical aspects of CF remained stable. Studies of sputum showed reduction in several inflammatory markers suggesting dampened neutrophil activity in the lungs with active treatment at the higher dose. Some blood markers of inflammation increased (including CRP) but without evidence of any clinical problems.
What does this mean and reasons for caution?
SB-656933 appears to have some impact on CF inflammation. However, our studies of blood levels indicate that most patients did not receive sufficient doses of the investigational medicine to optimize its activity. We also need to understand what the significance and clinical relevance of increased blood inflammatory markers might be, and to further establish safety in longer and larger clinical trials.
We are currently considering our options for SB-656933. Based on the results of the research we have seen so far, no clinical work is either planned or underway for SB-656933, although the option remains open to conduct additional research in the future.