new medicines

Question

What can you tell us about new medicines to be expected? How are the examinations and tests progressing? What are the expectations of the medicines and when are they expected to come on the market? Are they meant for delF508?

Answer

Dear questioner,

You ask about new medicines in the pipeline. This is of course a very general question, I will therefore narrow it down to medicines aimed at improving the underlying defect in CF. The good news is that this research has progressed well in the last years.

The first medicine that improves the underlying defect in CF is on the market. This drug, ivacaftor, ensures a better function of the CFTR chloride channel in patients who carry the G551D mutation. This mutation belongs to class 3 (read more in the Archive under CFTR mutation classes): mutations that lead to a CFTR protein that gets to the surface, but fails to open. Drugs that improve the opening of the CFTR channel are called "potentiators". G551D patients treated with this drug had better lung function, better weight, felt better and had less exacerbations of lung infection. Unfortunately this mutation is only present in about 4% of CF patients worldwide. It is currently being tested in patients who carry other class 3 mutations (about 1% of patients with CF).

But there is also very intensive research for patients who have the common F508del mutation, a class 2 mutation. This mutation leads to production of a protein that is broken down by the cell quality control so that it does not get to the cell surface. Medicines that rescue protein from being broken down this way are called “correctors”. A corrector (VX-809) was tested with addition of a potentiator to improve chloride function in patients who carry 2 F508del mutations. This combination produced some improvement in sweat chloride and also some improvement in lung function. That is why this combination of drugs will be further tested in larger numbers of patients with two F508del mutations.

But also on the basic level there is improved understanding of why correction of the abnormal CFTR protein is so difficult. To allow for normal travel to the cell membrane, the CFTR protein must not only take on a very specific shape, but also tight connections must be made between the different components of the protein. In cell research it now seems that correction of these 2 aspects are needed before a really substantial amount of abnormal CFTR protein will travel to the cell surface. It is hoped that this better understanding will help to find better correctors, or combination of correctors.

We hope that this information is clear and fulfill your needs.
Prof. Kris De Boeck

10.01.2013