SUMMARY

• The company cannot recommend any practices, procedures, or usage of IMAAVY that deviate from the approved labeling.
• Please refer to the local labeling for relevant information regarding vaccinations with IMAAVY.
• In a post-hoc analysis of the VIVACITY-MG3 study, IMAAVY was assessed for its 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.^1,2 
• In a randomized, phase 1 study (NCT05827874), the effect of IMAAVY on vaccine response was evaluated in healthy adult participants.³ 

Clinical Data

Post-hoc Analysis

Yu et al (2025)² conducted a post-hoc analysis to assess the impact of IMAAVY on pre-existing clinically relevant anti-vaccine antibodies and humoral response to SARS-CoV-2 challenge in patients enrolled in VIVACITY-MG3 study.

Study Design

• The VIVACITY-MG3 study is a phase 3, randomized, multicenter, double blind, placebo (PBO)-controlled clinical trial that evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of IMAAVY in adults with generalized myasthenia gravis (gMG).
• Patients (≥18 years of age) with anti- acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK) or low-density lipoprotein receptor 4 (LRP4) antibody positive or seronegative (in all countries except France) gMG (Myasthenia Gravis Foundation of America [MGFA] Class IIa-IVb) were included in the study.
• The study consisted of a ≤4-week screening phase, followed by a 24-week, double-blind, PBO-controlled treatment phase, a variable-duration open-label extension (OLE) phase (up to 240 weeks in the European Union), and a safety follow-up at 8 weeks after the last infusion.
  • Patients who withdrew or discontinued after receiving any amount of the study intervention were required to complete a safety follow-up assessment at 8 weeks after the last dose.
• Eligible patients were randomized (1:1) to receive a loading dose of intravenous (IV) IMAAVY 30 mg/kg at week 0, followed by 15 mg/kg every 2 weeks (Q2W) or matching PBO through week 24, in addition to standard of care (SOC) therapy.
• Patients entering the OLE phase continued to receive IMAAVY 15 mg/kg Q2W in addition to SOC.
• Serum immunoglobulin G (IgG) antibody levels against tetanus toxoid (TT) and varicella zoster virus (VZV) were assessed at baseline and post-treatment in a subset of patients from VIVACITY-MG3.
• In patients with available samples and documented SARS-CoV-2 vaccination or infection, antibodies against different epitopes (spike, receptor-binding domain [RBD], and nucleocapsid) were measured.

Results 

• Treatment with IMAAVY reduced pre-existing anti-TT and anti-VZV antibodies similar to total IgG (median [interquartile range, IQR] pre-dose/minimal reduction at week 24: 68.8% [-62.2 to -75.3]); see Figure: Observed % Reduction in Anti-TT and Anti-VZV Antibodies in Patients with gMG.

• The majority of patients treated with IMAAVY who were immune to TT (n=18) and VZV (n=19) at baseline maintained IgG antibody levels above protective thresholds during the double-blind period, see Figure: Anti-TT and Anti-VZV IgG Levels Over Time in Patients Treated with IMAAVY and Anti-TT and Anti-VZV IgG Levels Above PT in Patients Treated with IMAAVY.

• One patient treated with IMAAVY received a TT vaccination during treatment and observed an increased and sustained anti-TT levels above the protective threshold post-vaccination.
• In patients treated with IMAAVY, SARS-CoV-2 vaccination (n=12) during treatment increased anti-spike antibodies. Data from 3 representative patients shown (see Figure: Response to SARS-CoV-2 Vaccination)

• In participants treated with IMAAVY, SARS-CoV-2 infection (n=10) led to increased anti-spike and anti-nucleocapsid antibodies. Data from 3 representative patients shown (see Figure: Response to SARS-CoV-2 Infection).

Phase 1 Study

Cossu et al (2025)³ evaluated the effect of IMAAVY coadministration with tetanus toxoid, diphtheria, and acellular pertussis vaccine (Tdap) and 23-polysaccharide pneumococcal vaccine (PPSV^®23) on IgG response following vaccination in a phase 1, open-label study involving healthy adults.

Study Design 

• Healthy participants (≥18 years of age) were randomized (1:1) to receive either IMAAVY (active arm) or no drug (control arm). (See Figure: Phase 1 Vaccine Challenge Study in Healthy Volunteers).³  
  • The target population consisted of healthy male and female participants, 18 to 65 years of age, with no history of receiving a tetanus (eg, Tdap) vaccine in the past 5 years or a pneumococcal vaccine (eg, Prevnar 7, 13, and 20 or PPSV^®23) in the past 10 years.

• Secondary endpoints included the median percent change from baseline in total IgG levels, the proportion of participants with a positive IgG response to the Tdap vaccine over time, and the change from baseline in total anti-pneumococcal (PCP) IgG levels over time.

Results 

• Overall, 32 healthy participants (active arm, n=17; control arm, n=15) were randomized into the study.
• The time from previous Tdap vaccine booster was 9 years (range, 5-13) in the active arm (n=17) compared to 8 years (range, 5-16) in the control arm (n=15).
• The vaccine completers analysis included 29 participants (active arm, n=15; control arm, n=14) (see Figure: Reduction of Total IgG [Completers Analysis Set]).
  • In the active arm, 1 participant withdrew consent prior to receiving study drug and 1 participant discontinued after 1 dose due to an adverse event (AE).

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.⁴ 
  • Total IgG returned to baseline levels by week 16 in the active arm.

Anti-Vaccine Antibody Responses

• All participants showed a response to the Tdap Vaccine (see Figure: Response to T-cell-Dependent [Tdap] Vaccine [Completers Analysis Set]).
• The proportion of participants who met criteria of positive anti-TT IgG response at week 2 and week 16 in both groups were:
  • Week 2: active arm (60%) and control arm (71.4%)
  • Week 16: active arm (40%, 6/15) and control arm (28.6%, 4/14)
    • Median change from baseline in anti-TT IgG level: active arm (68.3%) and control arm (50.2%)
• All participants had anti-TT IgG levels ≥0.16 IU/mL at baseline and throughout the study.

• All participants mounted a response to the PPSV^®23 vaccine. Total median anti-PCP IgG levels were:
  • Week 16: active arm (336.6 mg/L; IQR: 140.0-521.1; median increase from baseline: 785.7%) and control arm (491.9 mg/L; IQR: 289.1-1028.5; median increase from baseline: 905%)
• All participants in both the active arm (93.3%) and control arm (100.0%) 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]).

Serotype-specific Anti-PCP IgG Response

• The proportion of participants 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]).

Safety

• Safety assessments were reported through week 16. See Table: Summary of TEAEs.

Literature Search

A literature search of Ovid MEDLINE^®, Embase^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 15 January 2026.