Johnson & Johnson Submits BLA for Nipocalimab, Aiming to Disrupt the Autoimmune Market with a Potential Blockbuster in gMG

Autoimmune diseases, often referred to by patients as "the cancer that doesn't kill," mainly include rheumatoid arthritis, ankylosing spondylitis, myasthenia gravis, psoriasis, Crohn's disease, systemic lupus erythematosus, etc. The pathogenesis of autoimmune diseases is complex, requiring long-term medication, and issues such as drug resistance and compliance are relatively common. Treatment often needs to be updated, which also drives the continuous development of the autoimmune disease drug industry.

In the past decade, the autoimmune field has formed a super track with a potential market space comparable to that of the oncology field. Even amidst a pharmaceutical industry downturn, interest in the development of targeted autoimmune drugs continues to grow. Emerging targets in the autoimmune field are constantly surfacing, with FcRn being one of them.

FcRn is a cell surface protein capable of binding to immunoglobulin G (IgG) antibodies. It is widely expressed throughout the body and can protect IgG antibodies from lysosomal degradation, thereby extending the half-life of IgG antibodies in the body. Therefore, by blocking the binding of FcRn and IgG antibodies, the clearance of harmful autoantibodies in the body can be accelerated.

The pathogenic mechanism of many autoimmune diseases lies in their autoantibodies. FcRn can treat autoimmune diseases known to be driven by pathogenic IgG antibodies, including generalized myasthenia gravis (gMG), pemphigus vulgaris (PV), primary immune thrombocytopenia (ITP), chronic inflammatory demyelinating polyneuropathy (CIDP), etc. Therefore, FcRn-targeted drugs can achieve the purpose of treating these autoimmune diseases.

The first success of the FcRn target in the autoimmune field was in myasthenia gravis (MG). In December 2021, Argenx's Efgartigimod received FDA approval for its initial indication, which was for the treatment of adult generalized myasthenia gravis (gMG) positive for anti-acetylcholine receptor (AChR) antibodies.

Subsequently, FcRn has attracted numerous enterprises from China and abroad to enter the field. The research and development not only focuses on gMG but also continuously extends to other autoimmune diseases. Currently, FcRn has become one of the popular targets in the autoimmune field.

The rise of FcRn has broken through with Myasthenia Gravis (MG), largely because the MG market is promising. Additionally, although there are many traditional drugs for MG treatment such as cholinesterase inhibitors, hormones, immunosuppressants, and immunoglobulins, current therapies have shortcomings in disease control and long-term safety. As an emerging targeted therapy, FcRn antagonists have been highly favored since their introduction.

As a first-in-class FcRn-targeting drug, Efgartigimod has shown remarkable commercial performance since its launch. Relying solely on gMG, its sales reached 400 million US dollars in 2022 and jumped into the billion-dollar club in 2023, achieving 1.191 billion US dollars.

According to Argenx's financial report, Efgartigimod saw accelerated sales growth in Q2 2024, with sales reaching $478 million, a year-on-year increase of 78%. As a result, Argenx achieved a profit of $29 million in Q2 2024, reversing the previous losses.

In addition to gMG, Efgartigimod is currently being tested for other autoimmune indications, including primary immune thrombocytopenia, pemphigus vulgaris/pemphigus foliaceus, and chronic inflammatory demyelinating polyradiculoneuropathy.

The success of Efgartigimod has prompted other companies in the FcRn space to intensify their research and development efforts. Just over a year after the approval of the second FcRn antagonist, Rozanolixizumab (approved in June 2023), Johnson & Johnson is also nearing the finish line.

Johnson & Johnson's Nipocalimab is considered a potential "best-in-class" antibody therapy targeting the neonatal Fc receptor (FcRn). By binding to FcRn, it prevents autoantibodies ingested by monocytes and endothelial cells from being released back into the bloodstream, instead degrading them within the cells. Studies have shown that it can reduce IgG levels, including pathogenic autoantibodies, in the bloodstream by more than 75%.

The marketing application for Nipocalimab is based on data from the Phase III clinical trial Vivacity-MG3. In the Phase III clinical trial Vivacity-MG3, after 24 weeks of treatment, the Myasthenia Gravis Activities of Daily Living scale (MG-ADL) scores decreased by 4.70 in the Nipocalimab plus standard therapy group and by 3.25 in the placebo plus standard therapy group, with a difference of 2.45 and a p-value of 0.002. The Quantitative Myasthenia Gravis scale (QMG) scores decreased by 4.86 and 2.05, respectively, with a difference of 2.81 and a p-value less than 0.001.

If Nipocalimab is approved successfully, it may become a strong competitor to Efgartigimod.

Nipocalimab was initially developed by AnaptysBio and later sold to Momenta. In August 2020, Johnson & Johnson acquired Momenta for $6.5 billion, bringing Nipocalimab into its portfolio.

Johnson & Johnson's Acquisition of Momenta: A Strategic Move for Nipocalimab

Autoimmune drugs are the largest business segment in Johnson & Johnson's pharmaceutical division. Clearly, Johnson & Johnson has invested significant effort into the autoimmune field, with earlier successes like Remicade (infliximab) and current contributors such as Stelara (ustekinumab), Tremfya (guselkumab), and Simponi/Simponi Aria (golimumab) generating substantial revenue.

In 2023, Stelara's annual sales reached a staggering $10.858 billion, becoming the core pillar of performance and accounting for 20% of Johnson & Johnson’s total pharmaceutical business revenue ($54.759 billion). In H1 2024, sales amounted to $5.336 billion, and it remained Johnson & Johnson's revenue engine. However, with Stelara's patent expiration, although products like Tremfya have successfully stepped in, it is evidently insufficient for Johnson & Johnson. The introduction of more new autoimmune products is crucial for Johnson & Johnson to solidify its position in the autoimmune field.

After the introduction of Nipocalimab, Johnson & Johnson has high hopes for the drug. In addition to gMG, Johnson & Johnson is also advancing clinical trials for chronic inflammatory demyelinating polyneuropathy (CIDP), rheumatoid arthritis, Sjögren's syndrome, warm antibody autoimmune hemolytic anemia (wAIHA), and hemolytic disease of the fetus and newborn (HDFN). Among these, the trial for warm antibody autoimmune hemolytic anemia has entered Phase III, while the trial for systemic lupus erythematosus is in Phase II.

The FDA has granted Nipocalimab Breakthrough Therapy designation for the treatment of pregnant women at high risk of severe Hemolytic Disease of the Fetus and Newborn (HDFN). Additionally, it has been awarded Fast Track designation by the FDA for the treatment of HDFN, gMG, warm antibody autoimmune hemolytic anemia (wAIHA), and Fetal Neonatal Alloimmune Thrombocytopenia (FNAIT).

Due to its potential to treat various autoimmune diseases, Nipocalimab was listed by the industry media Evaluate as one of the top ten potential blockbuster therapies in development earlier this year. Johnson & Johnson expects Nipocalimab’s peak sales to reach $5 billion.

The autoimmune field encompasses a wide variety of diseases, with a vast global patient population and significant unmet clinical needs, offering broad market potential. For multinational corporations (MNCs) facing patent cliffs and revenue bottlenecks, the autoimmune sector is indeed a goldmine.

At present, the火热的自免药物领域 is 暗流涌动. Global pharmaceutical companies are 加码狂奔 in the 自免市场. What surprises will Johnson & Johnson's Nipocalimab bring? 拭目以待.

References:

1. "FcRn Antagonists in the Treatment of Myasthenia Gravis (Review)" LgG Pioneer

2. "FcRn: Conquering the Autoimmune Market Once Again" PharmaResearch Network

3. "Autoimmune Drug Development Heats Up: How Many FcRn Antagonists Are in the Pipeline?" Boyao