Cystic fibrosis (CF) is a life-threatening disease, for which there is currently no treatment. There are some drugs on the market that, in certain cases, can alleviate the symptoms. In this article, we give a brief overview of the newest developments within this field and show how patient organizations can make a difference.
CF is a life-shortening metabolic disease affecting about 75,000 people worldwide and about 1 in every 10,000 Belgians (1). CF is caused by mutations in both copies of the CFTR gene. The CFTR gene codes for a protein that forms an anion transportation channel, which is involved in the production of sweat, digestive fluids and mucus. If the CFTR channel is not working properly, it results in a range of complications including thickened mucus in the lungs (causing frequent respiratory infections), exocrine pancreatic insufficiency, malnutrition and diabetes. CF cannot yet be cured, and the current treatments may take up to 4 hours per day. The condition leads to chronic disability and reduced life expectancy. The median age of death for a CF patient is only 27.5 years.
There are some drugs available
A lot of research is being done to find medicines to cure or alleviate CF. The companies Galapagos and Vertex are very active in this field and are developing drugs that consist of potentiators and correctors. A drug that enhances the anion transport through the CFTR channel is named a potentiator. A drug that supports proper formation of the CFTR channel, is named a corrector.
Ivafactor, a drug by Vertex marketed under the name Kalydeco, is a very effective potentiator and can greatly improve the condition of some CF patients. It only works for patients with a certain mutation, which occurs in only around 3% of the patient population.
Orkambi, also by Vertex, is the name of a combination pill containing ivafactor and the corrector lumafactor. This drug also works for patients who have the F508del mutation, and these patients account for 40% of the CF population. Orkambi is not yet reimbursed by the national public health system, but expectations are that it will be within the coming year.
Belgium is a real hot-spot, famous for our know-how in clinical trials.
Stefan Joris, managing director of the Belgian CF association, comments: “These drugs are very expensive and are therefore only prescribed and reimbursed to patients with the mutations for which the drugs showed a proven effect in clinical trials. Certain drugs might also work for other patients with other rare mutations, but this isn’t researched by the companies due to the small number of patients. To help these patients, a large-scale organoid project has been set up.”
Testing expensive drugs on organoids
In the organoid project, organoids (artificially grown cells that resemble an organ) are cultured in a specialized lab in Gasthuisberg in Leuven, starting from cells from CF patients taken during a rectal biopsy. The effectiveness of a drug can then be tested on these organoids. Joris says: “We see that drugs which work in clinical trials, also show a positive effect on the CFTR channels in the cultured organoids. This gives us a way to test whether a drug will also work for a patient who has a CFTR mutation, which is different from the one for which the drug was initially intended. If we can prove that the drug will also work for that patient, and if we could obtain an agreement with public health services, doctors could prescribe the drug and it would also be reimbursed.” In this way, very expensive and near impossible clinical trials, involving patients with all kinds of different mutations, can be circumvented and more patients can get access to treatment.
If we can prove that the drug will also work for that patient, and if we could obtain an agreement with public health services, doctors could prescribe the drug and it would also be reimbursed.
This project was set up and completely funded by the Belgian CF association, in collaboration with Dutch and Portuguese CF research centers. The initial set up cost was 800,000 euro, involving the investment in a high-end microscope of 300,000 euros and special pincers to make the biopsy as non-invasive as possible. “All patients can give us a sample for free at one of our centers and we will store it in our biobank for further research.”
The most frequent CFTR mutation is F508del and most new drugs are directed towards this mutation. On the one hand, this means that patients with F508del, often have the chance to participate in a clinical trial. On the other hand, patients with a less frequent mutation are left out. Joris concludes: “Belgium is a real hot-spot, famous for our know-how in clinical trials. A lot of contract research organizations with the right know-how are active here. This means that patients with F508del have many opportunities to take part in clinical trials. But at the same time they also feel overwhelmed with the demand, while patients with rare mutations keep on hoping to finally be enrolled. Nevertheless, the future looks positive. A new generation of CF drugs is being developed and is expected on the market within 3 years by companies such as Vertex and Galapagos, but also from other parties. These drugs can also be tested in our patient-funded organoid project!”
1. The prevalence of cystic fibrosis in the European Union, Farrell, Philip M.,Journal of Cystic Fibrosis , Volume 7 , Issue 5 , 450 - 453