Ustekinumab biosimilar shows clinical similarity to reference drug for plaque psoriasis

A phase III study presented at EADV 2023 demonstrated the similarity between SB17, a human monoclonal antibody and proposed ustekinumab biosimilar, and reference ustekinumab for the treatment of moderate-to-severe plaque psoriasis.

A total of 503 patients (mean age 44 years, >60 percent male) less than 95 kg were included in the analysis. They were randomized 1:1 to receive 45 mg of either SB17 or ustekinumab subcutaneously at weeks 0, 4, and 16. By week 28, patients originally on ustekinumab were re-randomized 1:1 to switch to SB17 or stay on their regimen, while those initially randomized to the biosimilar continued with their regimen every 12 weeks up to week 40. [EADV 2023, abstract 1320]

Eligible participants should have had a diagnosis of plaque psoriasis for at least 6 months, with or without psoriatic arthritis, with ≥10 percent body surface area involvement, Psoriasis Area Severity Index (PASI) ≥12, and Physician’s Global Assessment (PGA) score ≥3 (moderate). A washout period of prior psoriasis treatment (2 weeks for topical therapy; 4 weeks for systemic and phototherapy) was generally required prior to randomization.

At week 12, percent change from baseline in PASI was comparable between the SB17 and ustekinumab treatment arms, be it in the per-protocol set (PPS; least squares [LS] means, 85.7 vs 86.3) or full analysis set (FAS; LS means, 85.7 vs 86.4).

In the PPS, the adjusted difference in LS means of percent change from baseline in PASI by week 12 was −0.6 and the 95 percent confidence interval (CI) of the adjusted treatment difference was −3.78 to 2.58.

According to the researchers, SB17 and the reference drug were deemed equivalent if the 95 percent CI of the LS means difference of percent change from baseline in PASI at week 12 was entirely contained within the predefined equivalence margin of −15 percent and 15 percent for the PPS. The PPS results were well within the stated margin.

For the FAS, the adjusted difference in LS means was −0.7 and 90 percent CI was −3.34 to 1.93. “This was also within the predefined equivalence margin of −10 percent and 10 percent,” the researchers said.

In the FAS, 94 percent of SB17 recipients had a PGA score of 0 or 1 (‘cleared’ or ‘minimal’) by week 28; the corresponding rate in the ustekinumab arm was similar (92 percent). Mean Dermatology Life Quality Index scores dropped to 2.5 in both treatment arms.

The rates of any treatment-emergent adverse events (TEAEs) were also similar between the SB17 and ustekinumab arms at week 28 (48 percent vs 49 percent), as were the incidences of severe AEs (0.8 percent vs 0.4 percent) and TEAEs of special interest (28 percent vs 30 percent). About half of TEAEs were mild to moderate in severity, and TEAEs of special interest were mainly driven by infections.

In the pharmacokinetic analysis conduct­e­d on 142 participants (71 in each arm), the pharmacokinetic profiles of SB17 and ustekinumab were comparable based on the mean serum ustekinumab concentrations. In participants with overall antidrug antibody (ADA) negative up to week 28, mean concentrations were also similar between arms.

The overall incidence of ADAs up to week 28 was lower with SB17 than with ustekinumab (13 percent vs 39 percent).

“[Taken together,] our findings showed that SB17 and ustekinumab have equivalent efficacy and comparable safety and pharmacokinetics up to week 28 in patients with moderate-to-severe plaque psoriasis,” said the researchers.