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.