Switching Between Adalimumab Reference Product and BI 695501 in Patients with Chronic Plaque Psoriasis (VOLTAIRE-X): A Randomized Controlled Trial

Abstract

Background BI 695501 is an FDA-approved biosimilar to adalimumab reference product (RP). VOLTAIRE-X was a randomized clinical trial to assess outcomes with a biosimilar monoclonal antibody in line with the FDA requirements for designation as an ‘interchangeable’ biosimilar. Objective The aim of this study was to assess whether multiple switches between adalimumab RP and BI 695501 lead to equivalent pharmacokinetics and a similar safety and immunogenicity profile compared with continuous adalimumab RP. Methods We conducted a phase III, double-blind, randomized controlled trial between July 19, 2017, and April 16, 2019. There were 49 investigational sites across Europe and North America. Of 323 screened patients with moderate-to-severe chronic plaque psoriasis, 259 were treated with adalimumab RP during the run-in period. Of these, 118 and 120 were randomized to the continuous or switching arms, respectively. Interventions consisted of a run-in period with adalimumab RP 80 mg subcutaneously (SC) on Day 1, then 40 mg SC every other week (EOW) Weeks 2–12. Patients were then randomized to receive adalimumab RP 40 mg EOW Weeks 14–48 (continuous arm) or BI 695501 40 mg Weeks 14 and 16, adalimumab RP 40 mg Weeks 18 and 20, and BI 695501 40 mg EOW Weeks 22 to 48 (switching arm); all interventions were given SC. Primary endpoints were pharmacokinetics parameters, area under the plasma concentration–time curve (AUC τ ,30–32 ) and maximum observed drug plasma concentration ( C max,30–32 ), measured after the third switch during the Week 30–32 dosing interval. Results 238 patients (mean [standard deviation] age 44.9 [13.8]; 66.0% male) were treated in the switching ( n = 118) or continuous arms ( n = 120). Adjusted mean C max,30–32 was 7.08 and 7.00 μg/mL in the switching and continuous treatment arms, respectively; adjusted mean AUC τ ,30–32 was 2025.8 and 1925.9 μg h/mL. Point estimate for mean ratio for AUC τ ,30–32 was 105.2% (90.2% confidence interval [CI] 96.6–114.6), and 101.1% (90.2% CI 93.3–109.7) for C max,30–32 . Both CIs were within a predefined bioequivalence range of 80.0–125.0%. Treatment-emergent adverse events led to discontinuation in 0.8% and 1.7% of patients in the switching and continuous treatment arms, and Psoriasis Area and Severity Index (PASI) scores were highly similar in the two arms across the entire trial period. Conclusions Pharmacokinetic equivalence was demonstrated, with highly similar efficacy and immunogenicity, and comparable safety observed in patients with chronic plaque psoriasis who received either adalimumab RP continuously or who switched between ...

Overview of biosimilars for immune-mediated inflammatory diseases: summary of current evidence

“…VOLTAIRE-X (NCT03210259) was 1 of the first randomized controlled trials to report outcomes that met FDA criteria for interchangeable designation. 25 This 48-week phase 3 interchangeability trial randomized 238 patients with moderate-to-severe chronic PsO and receiving reference product Humira (adalimumab) to undergo switching to biosimilar Cyltezo (adalimumab-adbm) or receive continuous Humira. Results showed that switching 3 times between Cyltezo and Humira resulted in equivalent efficacy, PK, and immunogenicity, and comparable safety between the switching and continuous treatment groups.…”

“…If state law permits, an interchangeable biosimilar may be substituted by a pharmacist for its reference product without permission of the HCP. 18,25 Physician-mediated switching should be differentiated from nonmedical switching, which is defined as altering a treatment regimen in patients with stable disease for reasons such as drug formulary changes and/or cost reductions. 27 One of the concerns related to biosimilars in general and switching between a reference product and a biosimilar is immunogenicity.…”

Provider and patient knowledge gaps on biosimilars: insights from surveys

“…PROVIDER AND PATIENT KNOWLEDGE GAPS ON BIOSIMILARS severe chronic plaque psoriasis was then demonstrated in the phase 3 VOLTAIRE-X trial (NCT03210259). 48 VOLTAIRE-X data showed that switching several times between adalimumab-adbm and adalimumab reference product resulted in equivalent pharmacokinetics, efficacy, immunogenicity, and comparable safety in people with moderate to severe chronic plaque psoriasis. At week 32, the study met the primary end point, supporting the application of adalimumab-adbm as an interchangeable biosimilar for the adalimumab reference product.…”

Biosimilars in Dermatology Review

“…There have been >90 switching studies performed with biosimilars which have not revealed any significant issues. 13,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] This continued surveillance must remain a focus of pharmacovigilance programs to monitor biosimilars as they are on the market. 34…”

“…There have been >90 switching studies performed with biosimilars which have not revealed any significant issues. 13,16-33…”