SUMMARY  

• Nipocalimab is an investigational, fully human, high-affinity, aglycosylated, effectorless immunoglobulin G1 (IgG1) anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody thereby reducing levels of circulating immunoglobulin G (IgG) antibodies.^1-5 
• In a randomized, open-label, parallel, single-site, interventional study, the effect of nipocalimab on IgG response to T-cell–dependent/independent vaccines (tetanus, diphtheria, pertussis vaccine [Tdap]; pneumococcal polysaccharide vaccine [PPSV^®23], respectively) was evaluated in healthy adult patients.⁶ 
• In a post-hoc analysis, nipocalimab was assessed for the impact on pre-existing clinically relevant anti-vaccine antibodies and antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection.⁷ 

Clinical Data

Randomized, Open-label Study

Cossu et al (2024)⁶ evaluated the effect of nipocalimab on IgG response to T-cell-dependent/independent Tdap and PPSV^®23 vaccines in healthy adult patients.

Study Design 

• Healthy patients (≥18 years of age) were randomized (1:1) to receive either nipocalimab (active arm) or no drug (control arm). (See Figure: Phase 1 Vaccine Challenge Study in Healthy Volunteers).⁶ 
  • The target population consisted of healthy male and female patients, 18 to 65 years of age, with no history of receiving a tetanus (eg, Tdap, Td) vaccine in the past ≤5 years or a pneumococcal vaccine (eg, Prevnar 7, 13, and 20 or PPSV^®23) in the past ≤10 years.
  • This study assessed the following: total IgG median percentage from baseline, proportion of patients with positive IgG response to tetanus vaccine, change in anti-tetanus (anti-TT) and anti-pneumococcal (anti-PCP) IgG levels over time, and serotype-specific anti-PCP IgG response.

Results 

• The demographic and baseline characteristics were comparable across treatment groups.⁶ 
• Overall, 32 healthy patients (active arm, n=17; control arm, n=15) were randomized into the study. In the vaccine response completers analysis, 29 patients were included (active arm, n=15; control arm, n=14) (see Figure: Reduction of Total IgG [Completers Analysis Set]).⁶ 
• The time from previous tetanus toxoid, diptheria, and acellular pertussis vaccine (Tdap) booster was 8 years (range, 5-16) in the control arm (n=15) compared to 9 years (range, 5-13) in the active arm (n=17).⁶   

Pharmacodynamics – total IgG

• The observed median pre-dose (minimal) reduction in total IgG at week 4 was 65.9% in the active arm compared to an observed median increase of 8.2% in the control arm.⁶ 
  • Total IgG returned to baseline level by week 16 in the control arm.

Anti-Vaccine Antibody Responses

• All patients showed a response to the Tdap Vaccine (see Figure: Response to T-cell-Dependent [Tdap] Vaccine [Completers Analysis Set]).⁶ 
• The proportion of patients who met criteria of positive anti-TT IgG response at week 2 and week 16 was similar in both groups:⁶ 
  • Week 2: control arm (71.4%) and active arm(60%)
  • Week 16: control arm (28.6%, 4/14) and active arm (40%, 6/15)

• Except for 1 patients in the active arm at week 4, all patients in both the control arm (100.0%) and the active arm (93.3%) achieved both anti-PCP IgG levels ≥50 mg/L and a ≥2-fold increase in anti-PCP IgG levels at all time points from week 2 through week 16. (see Figure: Response to T-cell-independent [PPSV^®23] Vaccine [Completers Analysis Set]).⁶ 

Serotype-specific Anti-PCP IgG Response

• The proportion of patients with both a serotype-specific IgG level >1.3mg/L and a ≥2-fold increase in anti-PCP IgG response was lower in the active arm at week 4 (P=0.0381) and was comparable between study arms at week 16. (see Figure: Serotype-specific Anti-PCP IgG Response [Completers Analysis Set]).⁶ 

Post-hoc Analysis

Yu et al (2024)⁷ conducted a post-hoc analysis to assess the impact of nipocalimab on pre-existing clinically relevant anti-vaccine antibodies and antibody response to SARS-CoV-2 vaccination and infection.

Study Design

• IRIS-RA is a phase 2a, randomized, double-blind, placebo-controlled, parallel-group study, that investigated the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of nipocalimab in patients with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumor necrosis factor agent.⁸ 
  • Patients (≥18 years of age) were randomized 3:2 to receive either nipocalimab
  • 15 mg/kg intravenously (IV) every 2 weeks or a placebo IV every 2 weeks from weeks 0 to 10 (see Figure: IRIS-RA study).⁷ 
  • The study included a screening period, a double-blind treatment period (weeks 0–12) and a safety/PD follow-up period (weeks 12–18).⁸ 
  • The goal of the post-hoc analysis was to assess the impact of nipocalimab on pre-existing clinically relevant anti-vaccine antibodies and antibody response to SARS-CoV-2 vaccination and infection.⁷ 
  • The nipocalimab treatment significantly and reversibly reduced total IgG levels in patients with RA (see Figure: Observed Pre-dose (Minimal) Reduction
    in Total IgG in Patients with RA).⁷ 
    • Based on PK/PD modeling based simulations for nipocalimab 15 mg/kg IV administered every 2 weeks, median steady-state IgG reduction was predicted to be a maximum of 75% with a pre-dose (trough) of 64.5%. 

Results 

• Nipocalimab-treated patients were able to mount IgG response to SARS-CoV-2 infection.⁷ 
  • Patients with SARS-CoV-2 infection during nipocalimab treatment mounted IgG responses against spike protein S1 receptor-binding domain (S1 RBD), and nucleocapsid.
  • Four patients developed SARS-CoV-2 infections during the study (see Figure: Response to SARS-CoV-2 Infection).
  • Of the 4 patients with RA who developed SARS-CoV-2 infections during the study, 3 had mild infections, and 1 had a moderate infection. All resolved without complications.

• Patients treated with nipocalimab were able to mount IgG response to SARS-CoV-2 vaccination.⁷ 
  • Clinical experience in COVID-19 suggests that antibody responses to SARS-CoV-2 vaccination and infection are variable in magnitude and duration.
  • Two patients with RA who received SARS-CoV-2 vaccination during nipocalimab treatment elicited IgG responses against spike protein and S1 RBD only (see Figure: Response to SARS-CoV-2 Vaccination).
  • There were no SARS-CoV-2 infection reported for these patients.

Literature Search

A literature search of Ovid MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 16 December 2024.