Safety, Virologic Efficacy, and Pharmacokinetics of CT-P59, a Neutralizing Monoclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Protein: Two Randomized, Placebo-Controlled, Phase I Studies in Healthy Individuals and Patients With Mild SARS-CoV-2 Infection.

PURPOSE: Neutralizing antibodies can reduce SARS-CoV-2 cellular entry, viral titers, and pathologic damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, Phase I studies. METHODS: In study 1.1, healthy adults were sequentially enrolled to receive CT-P59 10, 20, 40, or 80 mg/kg or placebo. In study 1.2, adult patients with mild SARS-CoV-2 infection were enrolled to receive CT-P59 20, 40, or 80 mg/kg or placebo. Primary objectives of both studies were safety and tolerability up to day 14 after infusion. Secondary end points included pharmacokinetic properties. Study 1.2 also measured virology and clinical efficacy. FINDINGS: Thirty-two individuals were randomized to study 1.1 (6 per CT-P59 dose cohort and 8 in the placebo cohort). By day 14 after infusion, adverse events (AEs) were reported in 2 individuals receiving CT-P59 20 mg/kg (headache and elevated C-reactive protein levels) and 1 receiving CT-P59 40 mg/kg (pyrexia) (all Common Terminology Criteria for Adverse Events grade 1). In study 1.2, 18 patients were randomized (5 per dose cohort and 3 in the placebo cohort). Sixteen AEs were reported in 10 patients receiving CT-P59. No AEs in either study led to study discontinuation. Greater reductions in viral titers were reported with CT-P59 than placebo in those with maximum titers >105 copies/mL. Mean time to recovery was 3.39 versus 5.25 days. IMPLICATIONS: CT-P59 exhibited a promising safety profile in healthy individuals and patients with mild SARS-CoV-2 infection, with potential antiviral and clinical efficacy in patients with mild SARS-CoV-2 infection. ClinicalTrials.gov identifier: NCT04525079 (study 1.1) and NCT04593641 (study 1.2).

Infliximab Biosimilar CT-P13 Observational Studies for Rheumatoid Arthritis, Inflammatory Bowel Diseases, and Ankylosing Spondylitis: Pooled Analysis of Long-Term Safety and Effectiveness.

INTRODUCTION: Long-term, real-world safety and effectiveness data are required to support biosimilar use. This analysis pooled 5-year findings from observational studies of infliximab biosimilar CT-P13 treatment in patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS). METHODS: Patients enrolled in the CT-P13 4.2, 4.3, or 4.4 Korea/European Union registries were analysed if they had initiated infliximab treatment with CT-P13 (CT-P13 group) or had switched from reference infliximab to CT-P13 (switched to CT-P13 group). The primary objective was to investigate long-term safety by evaluating adverse events of special interest (AESIs) per the CT-P13 risk-management plan. Incidence rates per 100 patient-years (PYs) were calculated. Additional long-term safety endpoints, immunogenicity (assessments optional), and effectiveness were evaluated. RESULTS: Overall, 736 patients (642 CT-P13; 94 switched to CT-P13) were analysed. Median (range) exposure to CT-P13 was 19.433 (0.03-63.11) months overall. The incidence of treatment-emergent adverse events was 69.0% (CT-P13 group) and 60.6% (switched to CT-P13 group). Infusion-related reaction/hypersensitivity/anaphylactic reaction was the most frequent AESI overall, with an incidence of 4.3828 per 100 PY (95% confidence interval: 3.3603-5.6185). For most AESIs, incidence rates per 100 PY were broadly comparable between treatment groups, considering overlapping 95% confidence intervals. At baseline, 42/445 (9.4%) and 21/59 (35.6%) evaluable patients in the CT-P13 and switched to CT-P13 groups, respectively, were antidrug antibody (ADA)-positive. After CT-P13 treatment during the study, 188/425 (44.2%) evaluable patients had ≥ 1 ADA-positive result, including 147/425 (34.6%) patients with negative or no ADA results reported at baseline. Effectiveness tended to increase over time for all indications. CONCLUSION: The analysis did not identify any new safety findings for patients with RA, IBD, and AS treated with CT-P13 for up to 5 years in those who were infliximab-naïve at CT-P13 initiation, or those who had switched from reference infliximab to CT-P13. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02557295 (CT-P13 4.2; retrospectively registered on 23 September 2015); NCT02326155 (CT-P13 4.3; retrospectively registered on 25 December 2014); NCT02557308 (CT-P13 4.4; retrospectively registered on 23 September 2015).