A complex array of drugs lie in wait for the future of cystic fibrosis drug treatment

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The fight continues to gain access to the cystic fibrosis drugs Orkambi and Symkevi, as well as other treatments in the pipeline. Here we take a look at the current CFTR modulator drug pipeline, to see what the future might hold.

Potentiators, correctors and amplifiers – a quick recap

Licenced CFTR modulators work in one of two ways, and are frequently given in combination. Correctors will help to correctly fold the CFTR protein (as mutations mean the protein can’t correctly fold itself), and the potentiators help open the channel in CFTR to allow chloride out. More details on each of these combinations and who would benefit from taking them are available here.

A different type of CFTR modulator, called an amplifier, is currently under development by the biotech company Proteostasis Therapeutics. The drug increases the amount of protein that is made. It is designed to be taken as a triple combination with a potentiator and a corrector and is currently in phase 2 drug trials.

The most important thing to remember is that different people with CF have different problems with their CFTR protein, and correctors, potentiators and amplifiers all help to treat different issues in different ways.

Room for improvement

The potentiators and correctors currently licenced are all made by the company Vertex Pharmaceuticals, but there are other versions of potentiators and correctors under development by companies such as Flatley Discovery Lab, AbbVie and Proteostasis Therapeutics in addition to new compounds by Vertex Pharmaceuticals. These companies are looking to see if they can develop drugs to do the same job in a better way, or whether a combination of drugs working in slightly different ways could repair the function of the CFTR protein more effectively with less side effects.

The best treatment for YOU

As we look to the future it will be important to match the right combination of drugs to each person with cystic fibrosis. A good selection of correctors, potentiators, amplifiers and yet-to-be-discovered CFTR modifiers licenced and available for use could open the door to this personalised approach.

However, while we might know that a triple combination therapy could work in most people (approximately 90% of the CF population), if and when this treatment becomes available to people with CF it will still take a long time to work out which triple is the best combination for an individual with cystic fibrosis. Rather than subjecting each person to an exhaustive trial of different versions of different drug types, working out the best treatment for everyone could begin in the lab. Researchers are working on converting cells donated by people with CF into lung cells, using stem cell technology. As the lab-grown lung cells will have the same genetic make-up as individuals with CF, they should give an accurate prediction of the best CFTR modulators to use for that person.

In addition to demanding access to licenced medicines, here at the Trust we’ll continue to fund research to find any new way to treat CF – for specific genotypes and for everyone with CF irrespective of their genotype – and to support pre-clinical drug discovery. Once drugs make it to clinical trials we’ll work to accelerate clinical trial programmes.

Dr Janet Allen, our Director of Strategic Innovation, says: “Our focus is to ensure that the best treatments are available for each individual with cystic fibrosis, so they are can live a life unlimited by their condition. This means access to the medicines that are currently licenced but also working to ensure that there is a pipeline of new, better and safer drugs and innovative therapies that will become available in the future”.

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