Ozoralizumab exhibits long half-life, favorable pharmokinetics in rheumatoid arthritis
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Key takeaways:
- Ozoralizumab demonstrated favorable pharmokinetics over 52 weeks in patients with rheumatoid arthritis.
- The drug also showed stability regardless of most patient characteristics.
Ozoralizumab demonstrates a long half-life and favorable pharmacokinetics, as well as sustained efficacy, over 52 weeks in patients with rheumatoid arthritis, according to data published in Arthritis Research & Therapy.
“Ozoralizumab (OZR) is a next-generation TNF inhibitor with a bispecific structure linking two humanized anti–TNF Nanobody VHHs with a humanized anti–human serum albumin (HSA) Nanobody VHH,” Tsutomu Takeuchi, MD, PhD, of the Keio University School of Medicine, in Tokyo, and colleagues wrote. “In the present study, we investigated the [pharmacokinetics (PK)] profile and the effects of patient baseline characteristics and anti-drug antibodies (ADAs) on the PK and efficacy of OZR in Japanese patients with RA from the OHZORA and NATSUZORA trials.”
To investigate pharmokinetics of ozoralizumab (Ablynx NV), Takeuchi and colleagues analyzed data from the OHZORA and NATSUZORA studies, which were both randomized multicenter trials that evaluated the drug in patients with RA over 52 weeks from 2018 to 2020. Patients participating in the OHZORA trial had previously failed to demonstrate a strong response to methotrexate, while those in the NATSUZORA trial used conventional synthetic disease-modifying antirheumatic drugs but discontinued due to safety issues.
In both trials, trough concentrations were collected at baseline and at varying timepoints during administration and follow-up. The researchers measured anti-drug antibodies before the beginning of drug administration and again at various points during administration and follow-up. Anti-drug antibody evaluation was classified in several groups, including negative, positive before administration without an increase after administration, positive before administration with an increased titer after administration, or positive after administration.
Neutralizing antibodies were also evaluated, and patients who were positive for these at any time during the trial were classified as being positive for neutralizing antibodies.
According to the researchers, the maximum plasma concentration was achieved in 6 days among patients receiving ozoralizumab 30 mg and 80 mg, and the drug demonstrated an elimination half-life of 18 days. In addition, ozoralizumab exposure “correlated negatively” with body weight, but did not appear to be impacted by other variables, the researchers wrote. Anti-drug antibodies also demonstrated a limited impact on the efficacy of the drug across both trials.
“The results of the present study suggest that OZR has a long t1/2 and good PK properties that are unlikely to be influenced by patient background characteristics except for body weight,” Takeuchi and colleagues wrote. “The efficacy of OZR was investigated on the basis of PK, and the results showed that subcutaneous administration of OZR 30 mg at 4-week intervals, which is the recommended clinical dosage and administration frequency of OZR, was more effective when the trough concentration at week 16 was more than 1 g/mL.
“At week 52, however, efficacy was not dependent on the trough concentration,” they added. “Therefore, we suggest that the efficacy with long-term administration, such as 52 weeks, is independent of the trough concentration.”
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