Three modulator drugs are better than two in cystic fibrosis

The development of radically new treatments for cystic fibrosis (CF) proceeds apace. In February 2018 Archivist reported on trials of double-modulator therapies (tezacaftor-ivacaftor) that produced modest benefits (doi:10.1136/archdischild-2017–3 14 602). Adding a third agent could, in theory, further enhance the intracellular functioning of the defective CFTR protein by binding to different sites on the molecule, particularly in those with the most common Phe508del mutation.

Two such agents which showed promise in vitro were used in parallel multinational phase two randomised controlled trials, published simultaneously in the NEJM. Both involved adults only, but the implications for children are obvious. In both trials, about 120 CF patients with the Phe508del genotype who were already receiving tezacaftor-ivacaftor double therapy were randomised to receive in addition one of the two new oral agents, known as VX-659 and VX-445, or placebo, over 4 weeks. In the VX-659 trial the main spirometric outcome measure (FEV1) increased by...

from Archives of Disease in Childhood current issue https://ift.tt/2C9zKNQ