Preliminary findings suggest rozibafusp alfa effective and tolerable in RA

For the first time, the safety and tolerability of multiple ascending doses of rozibafusp alfa was reported in patients with rheumatoid arthritis (RA) [1]. An interim analysis of a phase 1b study showed greater numerical improvement from baseline in Patient and Physician Global Assessments of Disease Activity (PtGA and PhGA) compared with placebo, as well as a non-linear, target-mediated disposition.

Rozibafusp alfa (AMG 570) is a first-in-class bispecific antibody-peptide conjugate targeting T-cell and B-cell activity by inhibiting both the inducible costimulator ligand (ICOSL) and the B cell-activating factor (BAFF). This phase 1b study reported on the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of rozibafusp alfa in RA patients. Enrolled in the study were 34  patients aged between 18 and 75 years with active RA defined as a disease activity score (DAS28-CRP) >2.6. Patients were randomised 3:1 to receive rozibafusp alfa or placebo subcutaneously every 2 weeks for 10 weeks (6 doses) into 4 separate groups of ascending doses of rozibafusp alfa, with 24 weeks of follow-up. All patients were also treated with a stable dose of methotrexate. Primary endpoint of the study was the subject incidence of treatment-emergent adverse events (TEAEs).

The results of the interim analysis show that rozibafusp alfa was generally well tolerated by patients. TEAEs 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 TEAE was upper respiratory infection (23.1%) for subjects receiving rozibafusp alfa and nasopharyngitis (37.5%) for subjects receiving placebo. No grade ≥3 treatment-related AEs were observed. Although 11.1% 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.

Based on the findings of this trial, further research is underway, with a phase 2, randomised, placebo-controlled study to assess the efficacy and safety of rozibafusp alfa in subjects with active systemic lupus erythematosus (SLE) and inadequate responses to standard-of-care therapy.

1. Abuqayyas L, et al. Abstract FRI0084. EULAR E-Congress, 3-6 June 2020.

Posted on 14 August 20206 January 2021