Oral delivery of an ustekinumab biosimilar with bioavailability comparable to subcutaneous administration in healthy human participants

PURPOSE: Ustekinumab, targeting interleukin (IL)-12 and IL-23, is effective in treating chronic immune-mediated inflammatory diseases, but needs to be dosed via subcutaneous (SC) injection, which impacts patient comfort and treatment adherence. To enable oral dosing of ustekinumab, the utility of a robotic pill (RP) was evaluated in humans. METHODS: A Phase 1 study was conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of single doses (0.5 and 0.75 mg) of an ustekinumab biosimilar (CT-P43) delivered via RP (RT-111) in healthy participants compared to ustekinumab (0.5 mg) administered via SC injection. RESULTS: RT-111 was well-tolerated with no reported SAEs. Ustekinumab was detected in 35/40 participants dosed with RT-111. At the 0.5 mg dose, RT-111 and SC administration yielded similar Cmax (RT-111: 67 ± 7 ng/mL, SC: 56 ± 4 ng/mL), while a dose-proportional increase in Cmax was observed at the 0.75 mg dose (92 ± 8 ng/mL). Uptake via oral delivery was faster, with a Tmax of 3 vs. 10 days for the SC group. Bioavailability of RT-111 was comparable (81%) to that of SC injection. CONCLUSION: This is the first report of successful oral delivery of a therapeutic antibody via an orally ingestible RP in humans, with bioavailability comparable to SC injection. CLINICAL TRIAL NUMBER: Study was registered at Clinicaltrials.gov as NCT05890118 in May 2023.