cystic fibrosis
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A triple drug combination for treating the underlying cause of cystic fibrosis is currently under study. The preliminary results show a significant improvement in lung function.

Cystic fibrosis is a genetic disease affecting the chloride channels in the body. These chloride channels are called cystic fibrosis transmembrane conductance regulator (CFTR). The major body systems affected by this mutation are the respiratory system and the gastrointestinal system. Cystic fibrosis mainly manifests itself as chronic lung disease and a deficiency in digestive enzymes.

Chronic lung disease in people with cystic fibrosis is characterized by an increase in thick and sticky mucus and chronic lower respiratory tract infections. Individuals must take digestive enzymes before eating to help the digestion and absorption of nutrients. Children with cystic fibrosis usually have difficulty gaining and maintaining their weight.

New drugs aim to improve outcomes in patients with common mutations

Two new drugs have been developed that target specific mutations of the CFTR channel. These drugs bind to different locations on the CFTR channels. They have the potential to improve the health and survival of people with cystic fibrosis who have the most common mutations.

Researchers conducted two studies to test the efficacy and safety of the two drugs, currently referred to as VX-659 and VX-445. These two drugs are combined in a triple therapy with tezacaftor and ivacaftor. Tezacaftor and ivacaftor are two other CFTR corrector drugs that are already in use to treat cystic fibrosis.

In the first study, VX-659-tezacaftor-ivacaftor was given to 12 patients with the same genetic alteration of the CFTR genes. In the second stage of the study, the researchers randomly assigned 117 patients (who have the same CFTR genotype) to either the placebo or treatment group. They followed the patients for four weeks.

Both drug combinations improved respiratory function

After four weeks, the researchers noted that the patients in the treatment group showed significant improvements in lung function tests. These results were published in the New England Journal of Medicine.

The second study analyzed the efficacy and safety of VX-445-tezacaftor-ivacaftor and similar results were shown compared with placebo. Both drug combinations improved respiratory function and the scores on the respiratory portion of the Cystic Fibrosis Questionnaire. Side effects were also reported in both trials; however, only three out of the combined 122 patients discontinued therapy due to serious side effects.

Phase III clinical trials needed to confirm long-term safety of treatment

These new CFTR targeted drugs can potentially treat the underlying cause of cystic fibrosis, which are dysfunctional chloride channels. These two trials focused on the efficacy of each drug on respiratory function over a short period of time.

It is unknown whether these drugs are safe and effective for longer durations nor if these drugs can correct digestive dysfunctions. Researchers will need to conduct phase-III studies to confirm the long-term safety of these drugs. They also need to determine the drugs’potential to reverse other non-respiratory manifestations of cystic fibrosis.

Written by Jessica Caporuscio, PharmD

References

  1. Mayor, S. Cystic fibrosis: triple drug regimens that target defective ion channel improve lung function, studies show. BMJ Research News. 2018.
  2. Rosenstein, BJ. Cystic Fibrosis. Merck Manual Professional Version. 2017. https://www.merckmanuals.com/en-ca/professional/pediatrics/cystic-fibrosis-cf/cystic-fibrosis
  3. Symdeko. Vertex Pharmaceuticals Incorporated. https://www.symdeko.com/
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