kinds of mutations, Mueller said, is for in vitro data on specific mutations, which can provide the basis for new clinical trials, although he noted that carrying out clinical trials in many cases becomes more complicated since there may only be a few patients with a particular mutation. This applies as well to people who have residual function of CFTR channels. Though their disease tends to be milder, models showing that channel function can be improved can be used to move forward. In some of these cases, combination drugs may be required that enhance channel trafficking as well as conductance. “The hope is, at the end of the day, that almost everybody can benefit from at least the combination regimen and go back to a level that is almost nonsymptomatic,” he said. “That’s our ultimate goal.”
Mueller also noted that ivacaftor was chosen to be extremely selective for the CFTR channel. But this channel plays a role in other conditions, from bronchitis to problems with sperm maturation, which raises the possibility that it could be used in other settings.
Bringing people with cystic fibrosis almost back to normal produces tremendous savings in terms of hospitalization and co-medications, Mueller said. Furthermore, these people are able to go back to work and participate in daily life. Personalized medicine has the potential to make a dramatic difference in a person’s life, which creates powerful incentives to create and use such therapies.
One lesson from this experience, Mueller said, is that regulators have a strong interest in bringing the right therapy to the right patients. It is best to involve them early, sometimes across divisions of FDA, and to have a constructive and not adversarial dialogue. Also, regulations and regulators in other parts of the world differ from those in the United States. Harmonized regulatory procedures around the world would bring effective medicines to people faster.
Another important lesson involves the registration of people with a disease. Because cystic fibrosis is an orphan disease, Mueller said, people with the disease are registered, which means they have already been diagnosed and can be approached for the collection of biological samples. It is important for this registry process to be harmonized across different countries, which would help to standardize the data that are gathered and would provide for the wider collection of samples. Data collection and standardization are also occurring through such mechanisms as the Cancer Genome Atlas, Ho said, which is doing multidimensional profiling of a large number of cancer samples. Michelle Penny of Eli Lilly and Company added that during the development of pomaglumetad methionil, the company made the collection of DNA samples mandatory where local regulations and IRB approval allowed, with consents ranging from candidate gene study to whole-genome sequencing. Only by having these