For the first time, safety and tolerability results were reported for multiple ascending doses of rozibafusp alfa in patients with rheumatoid arthritis [1]. This showed greater numerical improvement from baseline in Patient Global Assessments (PtGA) and Physician Global Assessments (PhGA) as well as a non-linear, target-mediated disposition.
Dr. Lubna Abuqayyas (Amgen, USA) presented the interim analysis of a phase 1b study looking at the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of rozibafusp alfa in patients with rheumatoid arthritis. Rozibafusp alfa (AMG 570) is a first-in-class bispecific antibody-peptide conjugate targeting T- and B-cell activity.
The 34 participants were aged between 18 and 75 years with active rheumatoid arthritis (defined as a disease activity score [DAS28-CRP] >2). Patients were randomized 3:1 to receive rozibafusp alfa or placebo subcutaneously every 2 weeks for 10 weeks (6 doses), with 24 weeks of follow-up. Four cohorts were made to ensure 4 separate groups of ascending doses of rozibafusp alfa. All patients were also treated with a stable dose of methotrexate. The primary endpoint of the study was the subject incidence of treatment-emergent adverse events (AEs).
The results of the interim analysis show that rozibafusp alfa was generally well tolerated by patients. treatment-related AEs were seen in 92.3% of patients being treated with rozibafusp alfa and in 87.5% of those on placebo. Most of these events were Grade ≤2, and the most common treatment-related AE was upper respiratory infection (23.1%) for subjects receiving rozibafusp alfa and nasopharyngitis (37.5%) for subjects receiving placebo. No treatment-related AEs Grade ≥3 were seen. Although 11.1% of patients who received rozibafusp alfa developed anti-rozibafusp alfa antibodies, there was no correlation to safety or AEs.
The preliminary analysis of disease-related activity showed a trend for greater numerical improvement from baseline in PtGA and PhGA with rozibafusp alfa versus placebo in the cohorts receiving the 2 highest doses. Further research is underway, with a phase 2, randomised, placebo-controlled study to assess efficacy and safety of rozibafusp alfa in subjects with active systemic lupus erythematosus and inadequate responses to standard of care therapy based on the dose finding in this trial.
Source:
1. Abuqayyas L, et al. Safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of rozibafusp alfa in subjects with rheumatoid arthritis: interim analysis of a phase 1b randomized, placebo-controlled, multiple ascending dose clinical trial. Abstract FRI0084. EULAR E-Congress, 3-6 June 2020.