ABSTRACT
Observational Study (GOAL; NCT01521338) will hopefully provide further insight in due course.
As discussed earlier in this chapter, the major CFTR biomarkers include sweat chloride concentration, airway potential dierence measurements, and short circuit current measurements on intestinal epithelium most commonly obtained by rectal biopsy. e latter has not, to date, been used as a clinical trial outcome measure but the rst two of these were used in the phase 2 trials of ivacaor and sweat chloride also in both of the pivotal phase 3 studies. e following appear clear:
1. e degree of correction of biomarkers of CFTR function may be organ specific. Phase 2 trials of ivacaor1 reported large changes in sweat Cl− (which have since been recapitulated in phase 3 trials)2,3 but smaller and less consistent changes in nasal epithelial chloride secretion; changes in basal PD or amiloride response, reecting sodium hyperabsorption, were even less consistent. Conversely, the class I targeted oral compound, ataluren, reported signicant changes in nPD in phase 2 trials, but the compound did not lead to changes in sweat chloride.4
