Johnson & Johnson's $6.5B FcRn Blocker Nipocalimab (IMAAVY) Receives FDA Approval for Generalized Myasthenia Gravis

Today, the FcRn target in the autoimmune new track welcomes another strong contender.

Local time on April 30, Johnson & Johnson announced Nicarlimab（Nipocalimab，IMAAVY）AlreadyApproved by the U.S. FDA for marketing, used for treatmentGeneralized Myasthenia Gravis（gMG）Patient。This is the first and only FcRn blocker approved for the treatment of anti-AChR antibody and anti-MuSK antibody positive adult and pediatric gMG patients aged 12 years and above.

As of this point, Johnson & Johnson 2020Accuse44.8 billion yuan（$6.5 billion (calculated based on the average exchange rate in 2020)The FcRn monoclonal antibody, acquired at great cost, has finally borne fruit.It will become an important catalyst for the next wave of growth in Johnson & Johnson's autoimmune field.

Screenshot source: Johnson & Johnson official website

FcRn Antibody

Heavyweight Bomb in the Autoimmune Track

Myasthenia Gravis (MG)Is an acquired autoimmune disease,There are approximately 700,000 patients globally.[2]. Among them,Approximately 85% of patients will progress to generalized myasthenia gravis.（gMG）, characterized by fluctuating skeletal muscle weakness, leading to symptoms such as limb weakness, ptosis, diplopia, and difficulties in chewing, swallowing, speech, and breathing.

In patients with MG, the immune system mistakenly attacks proteins at the neuromuscular junction, producing pathogenic IgG antibodies, such as anti-acetylcholine receptor antibodies. （AChR）Antibodies, Anti-Muscle-Specific Tyrosine Kinase（MuSK）Antibody, Anti-Low Density Lipoprotein-Related Protein 4（LRP4）Antibody.These antibodies interfere with or block the signal transmission between nerves and muscles, leading to muscle weakness.。

Clearing IgG antibodies can effectively control the progression of MG. FcRn Plays a key role in prolonging the serum half-life of IgG. FcRn antibodies can block their binding with IgG, accelerate the catabolism of IgG, leading to a decrease in IgG levels, including the production of pathogenic autoantibodies, thereby treating diseases.

Previously, two FcRn antibodies have been approved globally for the treatment of myasthenia gravis, namely Argenx/Zai Lab'sEfgartigimod, UCB'sRozelimab。

Efgartigimod is the world's first approved FcRn antagonist, which has been approved overseas for the treatment of myasthenia gravis.(Intravenous and Subcutaneous), Chronic Inflammatory Demyelinating Polyneuropathy（(Subcutaneous only), Immune Thrombocytopenia(Intravenous only)。

24 Years,Efgartigimod Overseas Revenue $2.2 Billion, Up 83% Year-over-YearSuccessfully advanced to become a blockbuster in the autoimmune field. In China,Efgartigimod achieved sales of $93.6 million last year,With a growth rate as high as 835%, it has become the primary driver of Zai Lab's performance growth.。

The clinical application prospects of the FcRn target are not limited to the aforementioned indications; it also has the potential to treat a wide range of autoimmune diseases such as lupus nephritis, membranous nephropathy, pemphigus, and Sjögren's syndrome.

It is estimated that approximately 195 million people worldwide suffer from some type of autoantibody-driven disease. [3], the market potential is enormous. This is also why Johnson & Johnson is investing heavily in FcRn.

$6.5 Billion Bet

CoverableMore than 90% gMG Patients

In October 2020, Johnson & Johnson acquired Momenta Pharmaceuticals for $6.5 billion, primarily to bring the FcRn monoclonal antibody Nipocalimab under its umbrella, thereby expanding Johnson & Johnson's pipeline in the autoimmune field and solidifying its leading position.

Unlike efgartigimod and rozanolixizumab, which both belong to the FcRn antagonist class,Nicalimab is an FcRn blocker.. It can specifically bind to FcRn, block its binding with IgG antibodies, reduce the recycling and circulation of IgG antibodies, and fundamentally decrease the level of autoantibodies in the blood.

gMG is the first approved indication for Nicalimab. In terms of formulation, both intravenous and subcutaneous forms of Efgartigimod have been approved. As latecomers, Johnson & Johnson and UCB have also entered the market.Directly launched a subcutaneous injectable formulation, to enhance the competitiveness of the product. Compared with intravenous injection, which usually takes about 1 hour, subcutaneous injection can be completed within 30-90 seconds, greatly improving the convenience of administration and patient compliance.

Indications:Nicalimab andLike rozelimab, it can simultaneouslyCovering AChR antibody positive, MuSK antibody positive, these two types of antibody-positive patients account for gMG More than 90% of the total antibody-positive population,Coverage RatioEfgartigimod More Broadly(Limited to patients positive for AChR antibodies)。

Image Source: Insight Database

The FDA approval of Nicarylmonab was based on the results of the pivotal Phase III clinical study, Vivacity-MG3. The study enrolled a total of 199 patients who were unresponsive to current standard therapies.（SOC）Poorly Responsive Antibody PositiveAdult gMG patients. The primary endpoint is the Myasthenia Gravis Activities of Daily Living score during treatment weeks 22, 23, and 24 for antibody-positive patients.（MG-ADL）Compared with the baseline changes, secondary endpoints include the quantitative myasthenia gravis score. (QMG ) etc.

Vivacity-MG study data shows:

• At weeks 22, 23, and 24 of treatment, patients receiving nicarlimab + standard of careMG-ADL score improved by 4.70 points, significantly higher than the 3.25-point improvement in the placebo + SOC group (P=0.002)；

• In terms of the secondary endpoint QMG, compared with placebo + SOC, nicarlimab + SOCOMG Score Improved by 4.86 Points(vs placebo group 2.05 points), the strength and function of different muscle groups in patients have significantly improved. (P<0.001)；

• Nicalimab + SOC GroupThe proportion of MG-ADL score improvement ≥2 points is 68.8%., while the value for the placebo + SOC group was 52.6%.（P=0.021)，further indicating that treatment with Nicalimab can reduce the impact of gMG on patients' daily lives.

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

Nicalimab treatment for gMG also demonstrates long-term efficacy and safety. The ongoing Phase III open-label extension study（OLE）The results showIndicates acceptanceNicarlimab Combined with Standard TreatmentgMG patients maintained a good condition during the 20-month follow-up.

At the same time, Johnson & Johnson is also conducting a project targetingAChR and MuSK Antibody Positive in Ages 12-17Adolescent gMG PatientsPhase Ⅱ/Ⅲ Pediatric Study（Vibrance）. The study data showed that nicarlimab in combination with SOC therapy achieved its primary endpoint, with a 69% reduction in serum total IgG levels within 24 weeks, and secondary endpoints MG-ADL and QMGc scores were both improved.

Outside the United States, applications for the marketing of Nicarelimab for Myasthenia Gravis have been submitted in Europe, Japan, and China. In China, Nicarelimab for gMG has been granted priority review by the CDE, which is expected to accelerate its approval.

The Successors in Johnson & Johnson's Autoimmune Pipeline

Nicarlimab is one of the many successors developed by Johnson & Johnson for its autoimmune pipeline.

Autoimmunity is the largest business segment of Johnson & Johnson's pharmaceutical division, maintaining a continuous growth trend over the past decade. In 2023, Johnson & Johnson's autoimmunity business revenue reached $18.052 billion, increasing by 129% compared to $7.87 billion in sales in 2012.

However,In 2024, Johnson & Johnson's autoimmune business revenue declined for the first time.（-1.2%）, sales dropped to $17.828 billion, marking the first time that the segment's revenue fell below its oncology business.($207.81 billion)。

Johnson & Johnson Autoimmune Business Historical Sales (Unit: Billion USD)

The main reason for the decline in revenue is that several key products have entered a sales decline phase due to factors such as patent expiration.

Infliximab（Remicade）Once the top revenue-generating product in Johnson & Johnson's immunology portfolio, it reached its sales peak in 2016 with an annual income of $8.234 billion. Following the expiration of its patent, sales have been declining consecutively since 2017, and by 2024, the sales had dropped to only $1.605 billion.(Down -12.8% year-on-year)。

Ustekinumab（Stelara）First approved in 2016, it quickly rose to become Johnson & Johnson's top revenue-generating product, with sales reaching $10.858 billion in 2023, making it a super blockbuster. As the patent expired, Ustekinumab's revenue also saw its first decline in 2024.（-4.6%）, amounting to USD 10.361 billion.

Golimumab（Simponi/ Simponi Aria）Sales were also not optimistic, with a slight 0.3% drop to $2.19 billion in 2024.

Source: Johnson & Johnson 2024 Earnings Report

Faced with the dilemma of consecutive revenue declines from several blockbuster products, Johnson & Johnson is actively responding, hoping to launch successor products to reverse the downward trend in performance.

IL-23 InhibitorGuselkumab（Tremfya）It is the first successor launched by Johnson & Johnson, available in both intravenous and subcutaneous formulations. It was first approved in 2017 as the first fully human, dual-mechanism interleukin-23 inhibitor. It has been approved in multiple countries and regions, including Europe, the United States, Japan, and China, with indications covering plaque psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease.

Since its launch, Guselkumab has maintained rapid growth for 24 years.Sales amount to$3.67 billion, a year-on-year increase of 16.6%。The rise of Guselkumab has partially offset the impact of the decline in the aforementioned three products, thereby enabling Johnson & Johnson's autoimmune business.Last year, it only appearedA slight decrease of -1.2%.

Currently, Johnson & Johnson is accelerating the expansion of the indications for Guselkumab, with several new indications expected to be approved by 2025, including ulcerative colitis.(Subcutaneous induction), Crohn's Disease(Approved), pediatric psoriasis, juvenile psoriatic arthritis, etc., are expected to enter a period of accelerated growth in the future.

Historical Sales of Guselkumab

The newly approved Nicallimab also shows great potential. In addition to gMG, Johnson & Johnson is currently exploring the drug's efficacy in treating various autoimmune diseases in clinical trials, including idiopathic inflammatory myopathy, Sjögren's syndrome, immune thrombocytopenia, rheumatoid arthritis, hemolytic disease of the newborn, and warm antibody autoimmune hemolytic anemia.（wAIHA）, systemic lupus erythematosus, lupus nephritis, chronic inflammatory demyelinating polyneuropathy, etc. Among them,wAIHA Indication Expected to Submit to FDA in 2025Marketing Application。

In addition, Johnson & Johnson has developed several powerful tools in the autoimmune field, including an oral IL-23R antagonist and an IL-13/TSLP bispecific antibody.（PX128）、IL-13/IL-22 Bispecific Antibody（PX130）IL-31/IL-4Rα Bispecific Antibody（NM26）Etc. All three bispecific antibody products were acquired through external company acquisitions.

It is not difficult to see that Johnson & Johnson's R&D focus in the autoimmune field has shifted, moving from primarily targeting IL-17 and IL-23 for development in the past to now establishing a differentiated portfolio of autoimmune bispecific antibodies.

If the development goes smoothly, these successors are highly expected to become new catalysts, leading Johnson & Johnson's autoimmune business back to growth.

Johnson & Johnson's Clinical-Stage Autoimmune Pipeline

Cover Source:ZCOOL Hailo

Disclaimer:This article is for information sharing only and does not represent the position or viewpoint of Insight. It does not recommend or introduce any treatment plans. If necessary, please consult and contact正规医疗机构.

Editor：Xin Medicine

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