Recent iva studies
As introduced above, iva was expanded to children ≥ 4 months, with the
data published in the American Journal of Respiratory and Critical Care
Medicine in 2020. Iva was found to be safe and well tolerated in
children 4 to 12 months of age in a phase 3, multicenter, single-arm,
2-part study3. Twelve patients were included in the
4-day part A, to evaluate safety, pharmacokinetics and to demonstrate
the proper dose for part B. Seventeen patients participated in the
24-week part B, to evaluate safety. Iva was found to be safe, with no
cataracts detected, and lower rates of liver function test (LFT)
elevation (1 infant in this study) compared to prior iva studies in
12-24 month and 2-5 year old children. Severe adverse event (SAE) rates
were 8.3% (n=1 with thrombocytopenia felt to be due to omeprazole) in
part A and 23.5% (n=4, bronchiolitis, cough, viral respiratory tract
infection, and viral rash) in part B. None of the SAEs were felt to be
related to iva. Pharmacokinetics, sweat chloride reductions, and
maintenance of weight parameters were consistent with prior studies.
An open label extension study, including 3 multicenter trials, was
published evaluating long term iva in non-G551D gating
mutations4. Patients ≥ 6 years of age were followed
over 104 weeks; only 41 out of 121 people completed the trial, due to
commercial availability of the drug. No additional safety concerns were
revealed, only predictable adverse events (AEs) due to CF disease were
found (such as pulmonary exacerbation (PEx), cough, headache, sinus
congestion, increased sputum production, nasopharyngitis) with 2 SAEs
possibly related to iva (PEx and sinusitis). Despite limited completion,
efficacy was confirmed with mean absolute improvement in FEV1pp,
increased body mass index (BMI), decreased sweat chloride, and increased
CF Questionnaire-Revised (CFQ-R) respiratory domain scores.
Iva has been marketed in the United States since January 2012 and in the
United Kingdom since July 2012, so long term follow up data is
available. Using both the United States Cystic Fibrosis Foundation
Patient Registry (US CFFPR) and the United Kingdom Cystic Fibrosis
Registry (UK CFR), Higgins et al followed patients longitudinally
from date of starting iva5. Annual cross sectional
safety analysis was tracked over 5 years in a real world clinical
environment, extending the work of this group’s prior
longitudinal6, and one time cross-sectional
analysis7. The analysis demonstrated that iva had no
new safety concerns. Lower risk of death, lung transplantation,
hospitalizations, and PExs were seen and remained consistent across the
5 years analyzed.