Open label extension ETI trial
As described above, ETI was approved in October 2019 by the FDA for pwCF
≥ 12 years old, and an open label extension study is still ongoing. An
early interim analysis of the phase 3, open label extension trial
results for ETI through week 24, in 506 participants was
published8. Patients with F508del/minimal function
(F/MF) or F508del/F508del (F/F) mutations were included, allowing those
who were on placebo in primary studies9,10 to be
provided open label ETI. Efficacy was similar to the primary phase 3
studies, with increases in FEV1pp by 14.9% and 12.8%, in F/MF and F/F
participants, respectively, when transitioning from placebo to
ETI8. The reduction in annual PEx rate from 0.98 to
0.37 per year seen in the original F/F 24-week phase 3 study was
maintained in this extension trial. The rates of PEx were 0.3 events per
48 weeks in both the F/MF and the F/F groups. Sweat chloride, BMI and
CFQ-R respiratory domain scores also demonstrated similar improvements
compared to primary studies. Adverse events were similar to the primary
studies. Only 7 (1.4%) of AEs led to treatment discontinuation,
including liver events (n=4), depression (n=1), rash (n=1), and
tinnitus/contusion (n=1). Transaminase elevation above 3x normal
occurred in only 36 (7.1%) of the study population.