Rozanolixizumab, at doses ranging from 4 to 15 mg/kg, induced platelet responses in patients with primary immune thrombocytopenia (ITP), according to an interim analysis of an open-label, phase II trial. Lead author Tadeusz Robak, MD, PhD, from the Medical University of Lodz in Poland, presented findings from this analysis at the 24th Congress of the European Hematology Association.
Rozanolixizumab is a subcutaneous monoclonal antibody specific for the human neonatal Fc receptor that is designed to reduce pathogenic immunoglobulin autoantibodies, the researchers explained. This trial evaluated the safety and efficacy of the agent in patients diagnosed with primary ITP within three months of screening. At baseline, patients had a platelet count of <35×109/L.
All patients received weekly doses of rozanolixizumab, administered as five doses of 4 mg/kg, three doses of 7 mg/kg, two doses of 10 mg/kg, or one dose of 15 mg/kg. Following rozanolixizumab treatment, patients were followed for eight weeks to assess adverse events (AEs) at each dose level.
As of data cutoff (August 2, 2018), 54 patients had been treated with rozanolixizumab. The median number of prior therapies across the dosing cohorts ranged from 3.5 to 7, “suggesting a difficult-to-treat population,” the authors noted.
Most patients (72%; n=39) experienced at least one AE, with a total of 104 AEs experienced during the eight-week assessment period.
Treatment-related AEs were observed in one patient each in the 4-, 7-, and 10-mg/kg groups, and in eight participants who received 15 mg/kg. Headache was the most frequently reported treatment-related AE across dosing cohorts: 7% in the 7-mg/kg group; 8% in the 10-mg/kg group; and 42% in the 15-mg/kg group.
The researchers noted that all instances of headache were mild or moderate in severity.
Four serious AEs occurred during the study:
- bleeding from the genital tract (4-mg/kg group)
- thrombocytopenia (10-mg/kg group)
- thrombocytopenia (15-mg/kg group)
- platelet count decrease (15-mg/kg group)
However, the investigators reported that none of these events were considered related to treatment. No deaths or treatment discontinuations due to AEs were reported.
The researchers also evaluated clinical efficacy via platelet count assessment throughout the observation period, noting that clinically relevant improvements in platelet count (≥50×109/L) were observed across all dose groups, with responses increasing with dose intensity:
- 4 mg/kg: 33%
- 7 mg/kg: 33%
- 10 mg/kg: 50%
- 15 mg/kg: 67%
However, duration of response was not reported. Among patients with a baseline platelet count ≥50×109/L, responses occurred rapidly across all dosing groups, even within eight days of the first rozanolixizumab dose for:
- 1/5 patients receiving 4 mg/kg
- 2/5 patients receiving 7 mg/kg
- 3/6 patients receiving 10 mg/kg
- 7/8 patients receiving 15 mg/kg
Rozanolixizumab also appeared to reduce total immunoglobin G (IgG) concentration, with average decreases in total IgG concentration ranging from 43.6% after four 4-mg/kg doses to 63.8% after two 10-mg/kg doses.
The data from this interim analysis “support the rationale that targeting the natural IgG recycling mechanism could offer a new treatment paradigm for people with IgG-driven autoimmune diseases,” the authors concluded. However, these findings will need to be confirmed in larger, randomized trials with longer term-follow-up. The researchers noted that the study is ongoing, with patients receiving rozanolixizumab at once-weekly doses of 20 mg/kg.
The authors report relationships with UCB BioPharma, which sponsored the study.
Robak T, Kaźmierczak M, Jarque I, et al. Safety and Efficacy of an Anti-FCRN Antibody, Rozanolixizumab, in Patients with Primary Immune Thrombocytopenia: Interim Results of a Phase II, Multiple-Dose Study. Abstract #S850. Presented at the 24th European Hematology Association Annual Congress, June 15, 2019; Amsterdam, The Netherlands.