Johnson & Johnson's $6.5B FcRn Acquisition Nipocalimab Gains FDA Approval for gMG, Marking a New Era in Autoimmune Therapy

May 09, 2025 07:31 CST Updated 07:32

Johnson & Johnson

Medical Device R&D and Manufacturer

Keywords

Nicalimab; FcRn; Research Progress

Recently, Johnson & Johnson announced that its FcRn monoclonal antibody Nipocalimab (brand name: Imaavy) has been approved by the FDA for marketing. It is used to treat generalized myasthenia gravis (gMG) in patients aged 12 years and older who are positive for autoantibodies (anti-acetylcholine receptor [AChR] positive, anti-muscle-specific tyrosine kinase [MuSK] positive, or anti-low-density lipoprotein receptor 4 [LRP4] positive).

Nicalimab is a high-affinity, fully human, glycosylated, effector-null, pH-insensitive IgG1 monoclonal antibody that selectively blocks the neonatal Fc receptor (FcRn) to reduce the levels of circulating immunoglobulin G (IgG) antibodies, including pathogenic autoantibodies and alloantibodies.

The approval of Nicarelimab this time is based on the positive results of the Phase III clinical trial VIVACITY-MG3. This study is a randomized, double-blind, placebo-controlled, global multicenter trial aimed at evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of Nicarelimab (loading dose 30mg/kg, maintenance dose 15mg/kg, intravenous infusion every 2 weeks) in combination with standard of care (SOC) compared to placebo plus SOC in autoantibody-positive (AChR+, MuSK+, LRP4+) or negative gMG patients who have an inadequate response to SOC.

Results showed that the study met its primary endpoint. Compared with baseline, patients receiving nicarlimab in combination with standard of care (SOC) had an average improvement of 4.70 points in MG-ADL scores at weeks 22, 23, and 24, significantly higher than the 3.25 points in patients treated with placebo plus SOC (P=0.002). For gMG patients, a change of 1 to 2 points in MG-ADL score may mean the difference between normal eating and frequent swallowing difficulties, or between shortness of breath at rest and the need for a ventilator.

Change in 24-Week Average MG-ADL Score

Moreover, the study also met the key secondary endpoints: At weeks 22 and 24, measurements using the Quantitative Myasthenia Gravis (QMG) score showed that compared with placebo plus SOC, treatment with Nacalimab plus SOC resulted in significantly greater improvements in strength and function across different muscle groups (P<0.001). Additionally, at weeks 22, 23, and 24, Nacalimab plus SOC demonstrated a significantly higher MG-ADL response rate (≥2-point improvement from baseline) compared to placebo plus SOC (P=0.021).

In terms of safety, nicarlimab was generally well-tolerated, with an overall incidence of adverse events similar to the placebo + SOC group.

The approval of Nicarlimab will further consolidate Johnson & Johnson's leading position in the autoimmune field. It is worth mentioning that Nicarlimab was not independently developed by Johnson & Johnson; it was initially developed by AnaptysBio and later sold to Momenta. In August 2020, Johnson & Johnson acquired Momenta for $6.5 billion, bringing several drugs, including Nicarlimab, under its umbrella.

In addition to treating gMG, Nicalizumab also shows promise for treating autoimmune diseases such as Sjögren's Disease (SjD). The FDA has granted Nicalizumab Breakthrough Therapy Designation for the treatment of pregnant women at high risk of severe Hemolytic Disease of the Fetus and Newborn (HDFN) and moderate to severe Sjögren’s Disease, as well as Fast Track Designation for the treatment of HDFN, gMG, Warm Antibody Autoimmune Hemolytic Anemia (wAIHA), and Fetal Neonatal Alloimmune Thrombocytopenia (FNAIT). Given its potential for treatingThe potential for multiple autoimmune diseases,NicalimabIn the Evaluate column2025One of the top 10 potential blockbuster therapies expected to be launched within the year.

FcRn

Important Targets for the Treatment of Autoimmune Diseases

FcRn, the neonatal Fc receptor, is a type of Fc receptor located on the cell membrane surface. Its structure is similar to that of major histocompatibility complex (MHC) class I molecules and consists of a heterodimer composed of a heavy α chain with a molecular weight of approximately 50,000 and a light β2m chain with a molecular weight of 12,000, non-covalently bound together.

FcRn was initially discovered in neonatal intestinal epithelial cells and is considered a receptor responsible for transferring maternal IgG to the fetus. Subsequent studies found that FcRn can protect IgG and albumin from intracellular lysosomal degradation. Through FcRn-mediated pH-dependent recycling, the plasma half-life of IgG or albumin is extended, while those IgG and albumin that do not bind to FcRn will be transported to lysosomes for degradation.

IgG is the most abundant type of immunoglobulin in human serum, and its abnormal antibodies are a key factor in causing autoimmune diseases. Studies have found that blocking FcRn can selectively remove IgG antibodies from the serum, accelerating the clearance of autoantibodies in the body and achieving therapeutic effects for autoimmune diseases.

Previously, the FDA has approved two FcRn antibodies: Efgartigimod (Vyvgart) developed by Argenx/Zai Lab and Rozanolixizumab (Rystiggo) from UCB. Among them, Efgartigimod’s approved formulations include intravenous injection and subcutaneous injection, which were successively approved by the FDA in December 2021 and June 2023 for treating adult patients with AChR antibody-positive gMG. Additionally, the subcutaneous formulation of Efgartigimod was approved by the FDA in June 2024 for treating adult chronic inflammatory demyelinating polyneuropathy (CIDP), becoming the first FcRn blocker approved for CIDP treatment.

EfgartigimodMarket performance has been impressive, with sales reaching the $1 billion mark in 2023 and hitting $2.2 billion in 2024. Future sales of Efgartigimod are expected to continue growing, bolstered by a new growth driver—FDA approval in April 2025 for a pre-filled syringe version of Efgartigimod. This means patients no longer need to frequently visit hospitals for intravenous infusions or go to the doctor’s office weekly for injections; they can now self-administer at home, making clinical application more convenient.

RozelimabRozelimab is a weekly subcutaneous injectable FcRn-targeting monoclonal antibody that was approved by the FDA in June 2023 for the treatment of gMG patients who are AChR or MuSK antibody positive. In January 2025, the EU approved two new administration methods for rozelimab, allowing patients to self-administer the drug via an infusion pump or a new manual push injector after receiving training from healthcare professionals. According to publicly available data, rozelimab's sales reached $202 million in 2024, marking an explosive growth compared to its first-year sales of $19 million in 2023.

In addition to the above three drugs, there are multiple FcRn-targeted drugs under research and development globally, among whichBatoclimab(HBM9161) is progressing rapidly and has been resubmitted for marketing approval in China in July 2024, with the declared indication beinggMGBatoclimab is an anti-FcRn monoclonal antibody that HBM Medicine has licensed from HanAll Biopharma, with rights to develop, manufacture, and commercialize it in Greater China. In October 2022, HBM Medicine entered into a licensing agreement worth over 1 billion RMB with CSPC Group to co-develop Batoclimab in Greater China.

However, the prospects of Batoclimab are still full of uncertainties. As early as March 2023, Harbour BioMed announced that Batoclimab treatsgMG's IIIPhase clinical trial achieved positive research results. December 1, 2023,Harbour BioMed Announces Delay of Phase III Clinical Trial of Batoclimab to Collect Additional Long-Term Safety Data and Withdraws Drug's Marketing Application

Outside of China, Immunovant has obtained the global development rights for batoclimab from HanAll Biopharma. In March 2025, Immunovant announced the treatment using batoclimab.Positive results achieved in gMG and CIDP clinical trials. HoweverImmunovant Decides Against Submitting Batoclimab for Regulatory Approval Due to Concerns Over Potential Cholesterol-Elevating Side Effects Limiting Its Long-Term Clinical Use

Immunovant has not abandoned exploring the FcRn target and plans to prioritize the advancement of a new generation of FcRn antibodies.IMVT-1402Development.

IMVT-1402 isA differentiated FcRn antibody design. Since both albumin and IgG-Fc extend their half-life through binding to FcRn, and their binding epitopes overlap to some extent, IMVT-1402 only blocks the binding of Fc to FcRn but does not block the binding of albumin to FcRn. The published results of the Phase 1 clinical trial show that IMVT-1402Can significantly reduce IgG in a dose-dependent manner,But it does not affect albumin, and its effect on reducing IgG is similar to that of Batoclimab (which does impact albumin concentration), while it has almost no effect on LDL.

China's pharmaceutical company Staidson is also actively developing FcRn-targeted drugs, with its development ofSTSA-1301Is aRecombinant High-Affinity Humanized IgG4 Monoclonal Antibody Against Human FcRn. November 2023,STSA-1301 Approved for Clinical Use in China to Treat Primary Immune Thrombocytopenia (ITP).

Summary

The approval of Nicalumab not only enriches Johnson & Johnson's autoimmune pipeline but also further intensifies the competition for the FcRn target. Pharmaceutical companies in China are also actively laying out plans for the FcRn target, among which Harbour BioMed's Batoclimab has resubmitted its application for treatment.gMG'sThe marketing application is expected to be approved this year. If Batoclimab is approved, it will become the fourth drug targeting FcRn. Currently, the main indication for FcRn-targeting drugs is gMG, but as a target in autoimmune disease drug development, FcRn-targeting drugs have the potential to treat more autoimmune conditions such as Sjögren's syndrome, ITP, and others.

References

1. "FcRn: Conquering the Autoimmune Market Once Again". PharmaResearch Network. August 6, 2024.

2. "Global Battle for FcRn Inhibitors Intensifies! Johnson & Johnson Strikes with 'Acquisition + Application' Combo; China-Produced Innovative Drugs Urgently Need to Break Through Homogenization Dilemma". Biotech Forward. April 23, 2025.

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