Adalimumab Biosimilar Shows Equivalent Efficacy, Safety to Reference Humira for Psoriasis

The adalimumab biosimilar AVT02 developed by Alvotech exhibited no clinically significant differences in safety, efficacy, and immunogenicity profile compared with the reference drug Humira in patients with psoriasis. Findings were published recently in BioDrugs.

Indicated for the treatment of several rheumatic diseases, including rheumatoid arthritis, ulcerative colitis, and psoriasis, the introduction of adalimumab was noted by researchers to provide a powerful new targeted treatment option for patients whose needs were not being met with standard oral systemic therapies.

Among the formulations available for adalimumab, the higher concentration formulation (100 mg/mL) has been noted to be better tolerated, with less pain with each injection, and has been associated with greater adherence, fewer discontinuations, and longer time on therapy than the original adalimumab formulation.

However, the high cost associated with adalimumab and biologics overall have contributed to significant issues regarding access to care and health equity in patients. With 6 FDA-approved adalimumab biosimilars expected to enter the market beginning in 2023, the citrate-free high concentration formulation biosimilar, AVT02, is currently under FDA review and was given a positive approval recommendation from the European Medicines Agency.

In the double-blind, randomized, parallel-group, active control phase 3 study, researchers compared the efficacy, safety, and immunogenicity profile of AVT02 with the reference Humira drug in 413 adult patients with moderate-to-severe chronic plaque psoriasis.

Participants were randomized at a 1:1 ratio to receive 80 mg subcutaneously of AVT02 (n = 205) or originator adalimumab (n = 208) in week 1, then 40 mg every other week. Moreover, starting at week 16, those who had received originator adalimumab were re-randomized (1:1 ratio) to continue receiving originator adalimumab or to switch to AVT02 every other week until week 48, with the final efficacy endpoint at week 50. Patients who initially received AVT02 continued to receive AVT02 from week 16 to week 48.

The primary endpoint was the percentage improvement in Psoriasis Area and Severity Index (PASI) score at Week 16, with secondary efficacy endpoints including:

• Percentage improvement in PASI score at additional timepoints
• Change from baseline in Dermatology Life Quality Index (DLQI) score
• Number and percentage of subjects achieving static Physician’s Global Assessment (sPGA) responses of ‘clear’ or ‘almost clear’
• Comparison of adverse event profiles, anti-drug antibodies, neutralizing antibodies, and serum trough levels of adalimumab at steady state

In their findings, both patients treated with AVT02 and the originator adalimumab exhibited clinically similar percentage improvement in PASI score at week 16 (91.6% vs 89.6%, respectively).

“The 90% confidence intervals for the primary endpoint were within the pre-defined equivalence margin of ± 10% (90% CI, −0.76 to 5.29; 95% CI, −1.34 to 5.88),” noted the study authors.

Furthermore, comparable efficacy at week 16 was shown for both the AVT02-treated and originator adalimumab-treated groups for secondary endpoints of DLQI score (11.4-point vs 10.6-point improvement, respectively) and sPGA (90.5% in both groups achieving ‘clear’ or ‘almost clear’).

Efficacy in all treatment groups was shown to be maintained through week 50, including for patients who switched from originator adalimumab to AVT02, in percent improvement of PASI score, quality-of-life assessment, and sPGA.

“The safety, tolerability and immunogenicity profles between AVT02 and originator adalimumab were similar at Week 16, and this persisted in the switched and continued groups through Week 50,” they added.

Based on the study findings, researchers concluded that they anticipate AVT02 to offer patients with psoriasis both comparable efficacy and improvements in subjective quality of life that originator adalimumab has provided.

Reference

Feldman SR, Reznichenko N, Pulka G, et al. Efficacy, safety and immunogenicity of AVT02 versus originator adalimumab in subjects with moderate to severe chronic plaque psoriasis: A multicentre, double-blind, randomised, parallel group, active control, Phase III study. BioDrugs. Published online October 16, 2021. doi:10.1007/s40259-021-00502-w