Transformational Treatments in Cystic Fibrosis

Today is the UK CF Conference, Britain's largest event dedicated to multidisciplinary cystic fibrosis work. We were honoured this morning to have Preston W. Campbell III, MD, Executive Vice President for Medical Affairs at the Cystic Fibrosis Foundation (our US counterpart) deliver a keynote on transformational treatments. Below, Dr Campbell gives more insight into this groundbreaking work.

It is an exciting time in cystic fibrosis. We have achieved remarkable improvements in the health and survival of those living with CF in the U.S. and U.K. over the last several decades, primarily due to advancements in CF care and the development of new therapies targeting the symptoms of CF. 


By the late 1990s, we had learned a great deal about the recently discovered CF protein, CFTR, but that information had not been translated into new CFTR-based therapies. To spur the development of new treatments, the CF Foundation began a new program focused on applying new drug discovery technology to treating the basic defect—the faulty CFTR protein—and funded a number of novel research collaborations. 

Vertex was successful in identifying small molecule compounds that targeted CFTR, and in 2012, ivacaftor was approved for patients with the G551D mutation after clinical trials demonstrated that it was safe and had remarkable clinical benefits. 

It is likely that ivacaftor will treat 15% of CF patients as it is approved for other CF patient groups. The most common mutation, F508del, has an additional problem and requires a different approach to treat effectively. 

Recently, a Phase 3 clinical trial was completed in patients with two copies of F508del, who were treated with ivacaftor in combination with another potential therapy, lumacaftor. Patients on the combination drug experienced improvements in lung function, reduction in pulmonary exacerbations and improved weight gain. 

This combination therapy will now be submitted to regulatory agencies for approval for patients with two copies of F508del (50% of patients). Another corrector is being evaluated for patients with only one F508del mutation. 

In addition, a robust new screening effort has been underway for over three years that will improve the efficacy of treatment for those with one or two F508del mutations. New screens are also ongoing for those with rare mutations, including nonsense mutations. If these programs are successful, 98% of CF patients could potentially be treated with these transformational therapies. The remaining 2% of the CF population will need other approaches, such as gene therapy, that replace CFTR or strategies that bypass the defective protein. These potential new therapies hold great promise for the CF community, and I am proud to be a part of this effort.