Johnson & Johnson Submits BLA for Nipocalimab, a Potential First-in-Class FcRn Inhibitor for Generalized Myasthenia Gravis

On August 29 local time, Johnson & Johnson announced that it had submitted a Biologics License Application (BLA) to the FDA, seeking the world's first approval for its investigational neonatal Fc receptor (FcRn)-targeted antibody therapy, nipocalimab, for the treatment of generalized myasthenia gravis (gMG). This marketing application is based on data from the Phase III clinical trial, Vivacity-MG3.

It is reported that nipocalimab was initially developed by AnaptysBio and later sold to Momenta. In August 2020, Johnson & Johnson announced the acquisition of Momenta for $6.5 billion (equivalent to approximately RMB 44.6 billion based on the exchange rate of RMB 6.8605 per US dollar on August 31, 2020), thereby obtaining its core product pipeline, nipocalimab, to further strengthen its position in the field of autoimmune diseases.

Myasthenia Gravis (MG) is a rare chronic autoimmune disease that affects approximately 700,000 patients worldwide, with onset possible at any age. When patients with myasthenia gravis experience involvement of limb muscle groups, it is referred to as generalized myasthenia gravis. Over 85% (approximately 600,000 patients) of individuals with myasthenia gravis will progress to generalized myasthenia gravis (gMG) within 24 months of onset, characterized by extreme fatigue and significant difficulties in facial expression, speech, swallowing, and mobility, leading to severe muscle weakness that can be life-threatening and greatly impair the patient's physical function and quality of life.

Most patients with generalized myasthenia gravis have IgG autoantibodies, of which about 75%-80% are positive for acetylcholine receptor antibodies. FcRn antagonists have a unique mechanism of action, specifically and efficiently targeting the clearance of immunoglobulin G (IgG) with minimal impact on non-IgG immunoglobulins, thereby treating autoimmune diseases mediated by pathogenic IgG antibodies, including myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP), and pemphigus vulgaris (PV), and are considered a highly promising class of drugs for treating antibody-mediated autoimmune diseases.

Nipocalimab is a monoclonal antibody targeting the neonatal Fc receptor, which can selectively block FcRn to reduce the levels of circulating IgG antibodies, including autoantibodies and alloantibodies that cause various diseases. In June this year, Johnson & Johnson announced that its FcRn-targeted antibody therapy, nipocalimab, achieved positive results in the Phase 3 Vivacity-MG study involving patients with generalized myasthenia gravis, providing crucial support for this application for marketing approval.

Data show that in patients with generalized myasthenia gravis, the primary endpoint being improvement in MG-ADL score from baseline within 24 weeks, patients treated with nipocalimab in combination with standard of care (SOC) demonstrated better efficacy compared to placebo plus SOC.

Moreover, the trial met multiple key secondary endpoints: At weeks 22 and 24, measurements using the Quantitative Myasthenia Gravis (QMG) score showed significant improvement (P<0.001) in the nipocalimab+SOC group compared to the placebo+SOC group; at weeks 22, 23, and 24, the MG-ADL response (≥2-point improvement from baseline) was significantly higher in the nipocalimab+SOC group compared to the placebo+SOC group (P=0.021), further highlighting the potential of nipocalimab treatment to reduce the impact on daily life for patients with gMG.

The FDA and EMA have granted nipocalimab several key designations, including: the FDA granting the therapy Breakthrough Therapy designation for the treatment of pregnant women at high risk of severe hemolytic disease of the fetus and newborn (HDFN), as well as Fast Track designation for the treatment of HDFN, gMG, warm antibody autoimmune hemolytic anemia (wAIHA), and fetal and neonatal alloimmune thrombocytopenia (FNAIT). The EMA has granted it Orphan Drug designation for the treatment of pregnant women at high risk of severe HDFN.

In addition, due to its potential to treat a variety of autoimmune diseases, Nipocalimab was listed as one of the top ten potential blockbuster therapies in development by the industry media Evaluate earlier this year.

In fact, Johnson & Johnson's nipocalimab therapy originated from a $6.5 billion acquisition four years ago.

In August 2020, Johnson & Johnson announced the acquisition of Momenta for $6.5 billion, thereby gaining access to the latter's core product pipeline, nipocalimab, further deepening its presence in the autoimmune disease sector. In October 2020, according to relevant legal regulations, Vigor Sub, a wholly-owned subsidiary of Johnson & Johnson, proceeded with the related payment procedures. Previous press releases indicated that the key reason for Johnson & Johnson’s acquisition of Momenta was the anti-FcRn monoclonal antibody drug nipocalimab (M281). Johnson & Johnson regarded this as a clinically validated potential first-in-class product.

In recent years, autoimmune drugs have been a core pillar of Johnson & Johnson, with products such as Remicade (infliximab), Stelara (ustekinumab), Tremfya (guselkumab), and Simponi/Simponi Aria (golimumab) contributing significantly to its revenue.

Among them, Infliximab has contributed more than $90 billion in revenue to Johnson & Johnson since its launch. Another product, Ustekinumab, achieved sales of over $10 billion in 2023, also being a key pillar product for Johnson & Johnson.

However, both of these products are facing patent expiration issues. To fill the patent cliff, Johnson & Johnson is also actively seeking new breakthroughs, such as the FcRn antibody nipocalimab, the oral small-molecule IL-23 inhibitor JNJ-2113, and other autoimmune pipelines.

In addition to Johnson & Johnson's strong investment in FcRn monoclonal antibodies, several pharmaceutical companies, including Argenx, UCB, Zai Lab, CSPC Pharmaceutical Group, and Harbour BioMed, have also entered this field. Several products have already been successfully commercialized.

Outside China, as early as December 2021, the FDA had already approved Argenx's FcRn antagonist Efgartigimod (Chinese name: 艾加莫德) for marketing to treat adult patients with generalized myasthenia gravis who are positive for anti-acetylcholine receptor (AChR) antibodies. In 2023, the sales of Efgartigimod reached $1.19 billion. In May 2023, the FDA approved UCB’s FcRn antibody Rystiggo (rozanolixizumab) for marketing to treat adult patients with generalized myasthenia gravis.

In China, in January 2021, Zai Lab collaborated with Argenx for a $75 million upfront payment (totaling $175 million) to acquire the China rights to Efgartigimod. On July 16, 2024, Zai Lab announced that the National Medical Products Administration (NMPA) had approved the biologics license application for the subcutaneous injection of Efgartigimod, to be used in combination with standard therapy for the treatment of adult patients with generalized myasthenia gravis (gMG) who are positive for acetylcholine receptor (AChR) antibodies. Notably, this is the first subcutaneous injection formulation approved by the NMPA for the treatment of gMG in China, offering gMG patients more treatment flexibility and options.

In addition, according to the CDE announcement, on July 18, 2024, Harbour BioMed resubmitted the marketing application for its FcRn antibody Batoclimab to the National Medical Products Administration (NMPA) for the treatment of generalized myasthenia gravis. We look forward to more FcRn antibodies being approved for marketing, bringing more accessible products to the vast autoimmune market.

References:
1. China Science Forum, "Significant Breakthrough in Generalized Myasthenia Gravis: ADAPT Study Published in The Lancet Neurology!"

2. WuXi AppTec, "First! Johnson & Johnson’s Potential Blockbuster Therapy Hits Primary Endpoint in Phase 3, Regulatory Submission Imminent"