SUMMARY

• Nipocalimab, a high-affinity, fully human, aglycosylated monoclonal antibody, is an investigational agent being studied for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP).^1,2
  • Although the pathophysiology of CIDP is not well understood, clinical evidence suggests a role of pathogenic immunoglobulin G (IgG) autoantibodies.³
  • Since nipocalimab reduces the levels of circulating IgG, including levels of pathogenic IgG autoantibodies, it is hypothesized to be potentially effective in the treatment of CIDP.^3,4
• An ongoing, phase 2/3, multistage, multicenter, randomized, double-blind, placebo-controlled, parallel-group withdrawal study is evaluating the efficacy and safety of nipocalimab in adult patients with CIDP (NCT05327114).²

BACKGROUND

• CIDP is a rare, acquired, heterogeneous, autoimmune disorder characterized by inflammatory peripheral polyneuropathy due to immune-mediated demyelination of the peripheral nerves, leading to progressive sensory loss, weakness, and loss of reflexes.^5-8
• CIDP, particularly acute-onset CIDP (A-CIDP), presents with signs and symptoms similar to those of Guillain-Barré syndrome, including paresthesia, progressive weakness in the distal limbs, and difficulty in walking. Patients with A-CIDP often retain the ability to walk independently and exhibit respiratory or autonomic nervous system involvement.^9,10
• A global 2019 meta-analysis reported the prevalence of CIDP as 2.81 per 100,000 individuals (95% confidence interval [CI], 1.58-4.39), and the crude incidence of CIDP as 0.33 per 100,000 person-years (95% CI, 0.21-0.53).^9,11
  • CIDP is 1.4-4.4 times more prevalent in men than in women and can occur at any age. A higher incidence is observed in patients aged >55 years. ^9,11
• While the exact pathophysiology of CIDP remains unclear, both cellular and humoral components of the immune system have been implicated. Evidence suggests that several autoantibodies, including pathogenic IgG autoantibodies, targeting nodes of Ranvier and paranodes in patients with CIDP are likely to be pathogenic.^4,8,12

CLINICAL DATA

Phase 2/3 Study: ARISE

An ongoing, phase 2/3, multistage, multicenter, randomized, double-blind, placebo-controlled, parallel-group withdrawal study (ARISE) is evaluating the efficacy and safety of nipocalimab vs placebo in adult patients with CIDP.^2,3

Study Design/Methods

• The estimated enrollment is 201 patients.²
• The study consists of the following periods^2,3:
  • Screening: to determine eligibility.
  • Run-in: to determine if patients have active CIDP.
  • Treatment:
    • Stage A (open-label): Patients will receive open-label nipocalimab intravenously (IV) to determine clinically meaningful improvements in CIDP symptoms and functional ability. Responders will be eligible to enter stage B.
    • Stage B (double-blind): Patients will be randomized 1:1 to receive nipocalimab IV every 2 weeks (q2w) or placebo. Patients who relapse during this period will be discontinued and treated with rescue medication.
  • Open-label extension (OLE) (variable length): Patients will receive nipocalimab IV q2w.
  • Safety follow-up: A visit is required 8 weeks after the last infusion of nipocalimab, irrespective of when that infusion occurs.

Objectives

• Primary objective: Time to first occurrence of a relapse event (up to week 52) in stage B.²
• Secondary objectives: To evaluate the safety and tolerability of nipocalimab vs placebo and the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of nipocalimab.³
• Stage A key objectives: To assess the improvement in symptoms, disease severity, and disease progression with nipocalimab.³
• Stage B key objectives: To evaluate the efficacy of nipocalimab vs placebo in terms of time to CIDP disease progression and improved functional level relative to stage B baseline.³
• The study design is shown in Figure: ARISE Study Design.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 10 June 2024.