Rozanolixizumab Shows No Clinical Impact on CIDP in Long-Term Phase 2 Study

Author(s):

Treatment with rozanolixizumab was safe among patients with CIDP, resulted in reduced immunoglobulin levels as expected, but did not have an impact on efficacy.

Luis Querol Gutierrez, MD, PhD

Results from a phase 2a study (NCT03861481) and its open-label extension (OLE) showed that rozanolixizumab, an approved medication for myasthenia gravis and immune thrombocytopenia, did not show evidence of efficacy in patients with chronic demyelinating polyradiculoneuropathy (CIDP). Investigators noted that the lack of efficacy could be a result of the relatively high disease stability rate in the placebo group.¹

Otherwise known as CIDP01, the placebo-controlled, investigator-blinded study comprised of 34 patients with definite or probable CIDP who were randomly assigned to once-weekly subcutaneous infusions of rozanolixizumab 10 mg/kg (n = 17) or placebo (n = 17) in addition to subcutaneous or intravenous immunoglobulin (IgG) maintenance therapy. After 85 days of treatment, investigators observed no significant between-group differences in inflammatory Rasch-built Overall Disability Scale (iRODS) score, the primary end point (rozanolixizumab: least square mean [LSM], 2.0 [SE, 3.2] vs placebo: LSM, 3.4 [SE, 2.6]; difference, –1.5; 90% CI, –7.5 to 4.5).

Led by Luis Querol Gutierrez, MD, PhD, a neurologist at the Hospital de la Santa Creu, in Barcelona, Spain, the study results may have been impacted by the high disease stability rate in patients on placebo. “This stability rate could be the consequence of recruiting a low proportion of patients with active immunoglobulin-dependent disease or the use of an endpoint of disease deterioration, which has been shown to be associated with higher placebo response rates. Similar disease stability rates have been seen in other CIDP trials that required patients to have immunoglobulin-dependent disease, indicating that improved methods for identifying immunoglobulin dependency may be needed,” the study authors wrote.

In CIDP01, a similar proportions of patients requiring rescue medication was observed between those on rozanolixizumab (5 of 16; 31%) and placebo (5 of 17; 29%). Throughout this double-blind period, those on active treatment saw a reduction in IgG levels by more than 80% to a mean of approximately 2 g/L, with concentrations stabilizing by around day 36. Despite high neurofilament light chain levels observed in both groups, no clinically meaningful trends were reported following treatment.

In total, 21 patients entered the single-arm, long-term OLE (NCT04051944), also known as CIDP04, which continued to study efficacy and safety of rozanolixizumab. Throughout this time, 19 patients (90%) experienced a treatment-emergent adverse event (TEAE), with decreased blood IgG, headache, and fatigue as the most common. Of 8 patients who experienced decreased blood IgG, 6 had severe events (IgG <1 g/L), 3 of which were drug related. IgG values returned to normal ranges (7-16 g/L) after the final visit.

During CIDP04, investigators recorded no meaningful changes over time in iRODS, adjusted INCAT disability score, or clinician-assisted grip strength. In total, 10 patients, 6 who switched from placebo and 4 who continued on rozanolixizumab, relapsed based on combined assessments.

To the authors knowledge, this was the longest exposure to an FcRn inhibitor in a clinical study to date. In the OLE, exposure to rozanolixizumab was between 1-527 days in the placebo/rozanolixizumab group and 85-614 days in the rozanolixizumab/rozanolixizumab group, with a total of 17.5 patient-years of exposure across both groups.

Gutierrez et al concluded, "These results should inform future trial design, including further research into the identification of pathophysiological phenotypes of CIDP (particularly the role of IgG autoantibodies), improving population selection methods by using available biomarker screening and accounting for a high placebo stability rate in power calculations."

REFERENCE
1. Querol L, De Seze J, Dysgaard T, et al. Efficacy, safety, and tolerability of rozanolixizumab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a randomized, subject-blind, investigator-blind, placebo-controlled, phase 2a trial and open-label extension study. Neurol, Neurosurg & Psych. Published online May 10, 2024. doi:10.1136/jnnp-2023-333112