Adalimumab Biosimilar BI 695501 Exhibits Pharmacokinetic Equivalence for Treatment Switching

Psoriasis is a chronic disease that affects 2% to 3% of men and women.2 The disease is characterized by plaques and reddish scaly patches. Some women develop pustular psoriasis, which can be life-threatening if severe.3 Although most women with psoriasis notice symptom improvement during pregnancy, 10% to 20% have symptom deterioration.3 The effect of psoriasis on fetal health is unclear.2 Some studies have suggested that psoriasis, which is a TH1-driven disease, contributes to lower birth weight as observed in other TH1-driven diseases.2 The proposed negative effects of psoriasis on fetal health are usually linked to moderate or severe psoriasis. Topical corticosteroids are safe to use during pregnancy, but topical tar products, tazarotene, and retinoids are teratogenic and should be avoided.2,7 Ultraviolent B phototherapy is safe in pregnant women with moderate to severe psoriasis but may compromise folate levels.2 Limited data are available about the safety of biologics during pregnancy, and careful consideration is required before prescribing.2,7
Does switching between adalimumab RP and BI 695501 lead to equivalent pharmacokinetics and a similar safety profile compared with continuous adalimumab RP?

BI 695501 and adalimumab reference product (RP) have similar efficacy and immunogenicity outcomes and comparable safety outcomes for patients with moderate to severe chronic plaque psoriasis, according to data from a multicenter, randomized, double-blind, phase 3 clinical trial published in the American Journal of Clinical Dermatology.

Investigators included adult patients with moderate to severe chronic plaque psoriasis in the study. Patients received 14 weeks of adalimumab RP treatment. After week 14, patients with a 50% or greater reduction in the Psoriasis Area Severity Index (PASI 50) were randomly assigned 1:1 to either continuous adalimumab RP or switching between adalimumab RP and BI 695501, an FDA-approved biosimilar to adalimumab RP, through week 48. Investigators assessed pharmacokinetics and immunogenicity at baseline and every 4 to 10 weeks thereafter. PASI and static Physician’s Global Assessment (sPGA) scores were also assessed at screening, baseline, and regular intervals during treatment. The primary outcomes were pharmacokinetics parameters area under the plasma concentration-time curve (AUCT,30-32) and maximum observed drug plasma concentration (Cmax, 30-32), measured after the third switch during weeks 30 to 32.

There were 238 patients randomly assigned in the study: 118 to the switching group and 120 to continuous treatment.

For primary pharmacokinetics endpoints, the adjusted mean AUCT, 30-32 was 2025.8 and 1925.9 in the switching and continuous treatment arms, respectively. The adjusted Cmax, 30-32 was 7.08 and 7.00 µg/mL in the switching and continuous arms, respectively. Point estimates for the adjusted mean ratios of switching and continuous treatments for AUCT,30-32 and Cmax, 30-32 were 105.2% and 101.1%, respectively.

Adjusted mean Cmin, 30-32 was 4.91 μg/mL in the switching group and 4.58 μg/mL in the continuous group, respectively (point estimate for the ratios of the adjusted mean 107.3%; 90.2% CI 97.3-118.4). Median tmax, 30-32 was 72.7 hours (IQR, 71.1-120.0) in the switching group and 72.3 hours (IQR, 70.9-120.0) in the continuous group, respectively. Mean plasma concentration-time profiles in both groups were very similar over the entire study period.

The percentage of patients with PASI 75 responses at week 32 were highly similar between the 2 groups, as were PASI scores over time for the entire trial period. The percentage of patients with sPGA responses 1 or less at week 32 were very similar between groups. Immunogenicity results were very similar between groups regarding patients who were ADA or nAb positive at week 32.

Treatment emergent adverse events (TEAEs) were similar between the groups with the exception of nasopharyngitis, which was more common in the switching group. Most TEAEs were not serious. There were no patient deaths during the postrandomization treatment period.

The study was limited by the impossibility of simulating every clinical scenario that may occur in clinical practice when switching therapies.

“Pharmacist-level substitution can occur between the interchangeable biosimilar and the RP, but not between the RP and its other biosimilars, or between the interchangeable biosimilar and other biosimilars of the RP,” the study authors cautioned.

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Menter A, Cohen S, Kay J, et al. Switching between adalimumab reference product and BI 695501 in patients with chronic plaque psoriasis (VOLTAIRE-X): a randomized controlled trial. Am J Clin Dermatol. Published online August 7, 2022. doi:10.1007/s40257-022-00708-w