Vertex Trial Results and the Importance of CFTR Therapeutic Diversity

The CF community was delivered great news the other week: Vertex’s tezacaftor/ivacaftor combination treatment significantly increased lung function (ppFEV1) in patients 12 years or older with certain mutations of the CFTR gene (cystic fibrosis transmembrane conductance regulator).F 508 For those who are new to, or not too familiar with, CF, this new combination therapy aims to address the actual underlying issue of the defective CFTR protein that leads to dehydrated sticky mucus in people with CF.

In Vertex’s EVOLVE  study (NCT02347657), CF patients with double F508del (delta F 508) mutation were dosed with the combination therapy every 12 hours. After the end of 24 weeks, these patients demonstrated a significant increase in forced expiratory volume in one-second (FEV1) 4% greater than those given placebo.

In the EXPAND study (NCT02392234), patients had one copy of the F508del mutation and another residual function mutation. After completion of this study, patients dosed with tezacaftor/ivacaftor showed a statistically significant increase of 6.8% compared to those who were on the placebo.

The drugs serve to both traffic the CFTR protein to the surface of the cell and then aim to correct it at its source. If approved by the FDA, the medication would serve as another option for people with mutations such as homozygous F508del. In 2015, some patients were eligible to receive Orkambi (ivacaftor/Kalydeco and lumacaftor) — a medication designed to accomplish the same end points as the tezacaftor/ivacaftor study. This may lead some to wonder why its necessary to have multiple CFTR modulators for the same mutations on the market. To me, this strategy is crucial to benefit patients.

Within my personal network, I’ve seen friends who have benefitted tremendously from Orkambi, and I have seen others who have shown no improvement. CF is an incredibly complicated disease in terms of therapeutic outcomes or even struggles experienced from patient to patient. People with CF have different lung functions, people with CF grow different bacteria in their lungs, and people with CF may have underlying genetic variants that affect disease severity. We also see for the first time that 50% of people with CF are over age 18. It is because of all of these different sub-cohorts within CF that make diversity in CFRT therapeutics so important.

Lastly, as an advocate, I’m always left with an uneasy feeling seeing my mutation finding such great success in clinical trials. While this announcement from Vertex offers a potential therapeutic agent for the majority of the CF community, we must not forget that some people still may not have any CFTR medications available. The fight to cure CF spans far beyond F508del or even CFTR modulators. Many medications currently in clinical trials are agnostic of CF mutation — meaning that if they are approved, they could be eligible treatments for everyone with CF.

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