Adalimumab biosimilar, originator comparable in efficacy, safety in psoriasis treatment

A novel biosimilar for adalimumab was associated with bio-equivalent pharmacokinetics and safety as the reference product in patients with moderate to severe plaque psoriasis, according to study findings.

Alan Menter, MD, of Baylor Scott & White Health in Dallas, and colleagues investigated BI 695501 (Boehringer Ingelheim), an FDA-approved biosimilar to the adalimumab reference product, in a phase 3, double-blind, randomized controlled trial.

“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,” they wrote.

Specifically, the researchers assessed whether multiple switches between the two drugs yielded equal pharmacokinetics, safety and immunogenicity as continuous treatment with the adalimumab bio-originator.

Between July 19, 2017, and April 16, 2019, they screened 323 patients from 49 sites across Europe and North America. Of that group, 259 received continuous adalimumab reference product, dosed subcutaneously at 80 mg on day 1 followed by 40 mg every other week during a run-in period from weeks 2 through 12. Following the run-in period, 118 patients were randomly assigned continuous reference product, whereas 120 were assigned to switch between the reference product and biosimilar.

Protocols for the continuous group called for 40 mg every other week from weeks 14 through 48. For the switching group, patients received the biosimilar at 40 mg on weeks 14 and 16, the reference product on weeks 18 and 20, and then the biosimilar every other week from weeks 22 through 48.

The patient population had a mean age of 44.9 years (standard deviation, 13.8) and was 66% men.

Area under the plasma concentration-time curve and maximum observed drug plasma concentration served as the primary pharmacokinetic endpoints. They were assessed during the dosing interval at weeks 30 to 32, according to the findings.

Results showed that the adjusted mean maximum observed drug plasma concentration was 7.08 g/mL in the switching group, compared with 7 g/mL for patients treated continuously.

Similarly, adjusted mean area under the plasma concentration-time curve was 2,025.8 g x hour/mL in the switching group and 1,925.9 g x hour/mL in the continuous group.

The researchers also calculated the point estimate for mean ratio of switching and continuous treatments, which was 105.2% (90.2% CI, 96.6%-114.6%) for the area under the plasma concentration-time curve and 101.1% (90.2% CI, 93.3%-109.7%) for maximum observed drug plasma concentration. They noted that these confidence intervals fell within the range of 80% to 125%, which was the predefined threshold for bioequivalence.

Safety data showed that 0.8% of patients in the switching group discontinued due to a treatment-emergent adverse event, compared with 1.7% of patients in the continuous arm.

PASI scores were “highly similar” between the study groups for the duration of the analysis.

“Pharmacokinetic equivalence was demonstrated, with highly similar efficacy and immunogenicity, and comparable safety observed in patients with chronic plaque psoriasis who received either adalimumab [reference product] continuously or who switched between adalimumab RP and BI 695501,” the researchers concluded.