The Next Big Arena: Schizophrenia Therapeutics Attracts J&J, BMS, Zai Lab, and Luye Pharma

The psychiatric field is expected to welcome the next blockbuster drug.

On the evening of April 9, Johnson & Johnson announced that it had completed the acquisition of Intra-cellular. Through this acquisition, Johnson & Johnson will not only incorporate lumateperone...（lumateperone）Included in the囊中, also encompasses a clinical-stage pipeline with best-in-class potential, further enriching its布局in the mental health field.

It is reported that Johnson & Johnson previously spent $14.6 billion to acquire Intra-Cellular, a company specializing in central nervous system (CNS) therapeutic drugs. This amount exceeded the global pharmaceutical enterprise acquisition record set by Johnson & Johnson itself in 2024.

Johnson & Johnson's Sky-High Acquisition of Intra-Cellular Targets Lumateperone, Which Has Two Major Psychiatric Indications; Its Sales Performance Has Been Strong, Growing from $22.81 Million in 2020 to $464 Million in 2023, with an Estimated $685 Million in 2024.

This time, Johnson & Johnson's acquisition of Intra-Cellular is just a microcosm of the booming CNS field. The psychiatric drug market is becoming a new competitive focus for global pharmaceutical companies, also driving up the trend in this track, with acquisition amounts on the rise. Among these, Karuna was acquired by BMS for $14 billion, and AbbVie acquired Cerevel for $8.7 billion. MNCs' interest in CNS continues, with Biogen announcing on January 2025 that it will "bottom-fish" Sage at a total valuation of $442 million. However, can the high-stakes bet on the CNS track truly bring the expected market returns?

Compared with the fierce competition in traditional advantageous fields (such as oncology and immunology), there are still many unmet clinical needs in the CNS field. However, the field of drug development for CNS has always been considered a "tough bone" in the pharmaceutical industry. From unclear mechanisms to difficulties in verifying animal models and challenges in clinical development, each of these aspects poses an obstacle to the development of CNS drugs.

In November 2024, AbbVie announced the failure of two EMPOWER clinical trials for its core drug Emraclidine, acquired from Cerevel, which is a new schizophrenia medication used to treat acute exacerbation of psychotic symptoms.

In the same year, Neumora's schizophrenia treatment drug NMRA-266 was put on clinical hold by the FDA due to preclinical data showing that the drug triggered seizures in rabbits. NMRA-266 is a highly selective positive allosteric modulator of the M4 muscarinic receptor. In September 2024, Neurocrine's schizophrenia drug luvadaxistat entered its second clinical trial.IIThe failure in the trial ultimately led to the decision to halt the development of luvadaxistat (NBI-1065844). Prior to this, both Roche and Danish company Lundbeck had announced the termination of related pipelines.

Consecutive trial failures have highlighted the high-risk nature of CNS drug development, also indicating that the complexity behind the mechanisms of drugs in this field and broader new neuroscience projects far exceeds expectations.

In the acquisition announcement, Johnson & Johnson emphasized its nearly 70 years of experience in the neuroscience field, with multiple commercialized neurology drugs. Among them, the antidepressant nasal spray Spravato achieved sales exceeding $1 billion in 2024. In the research pipeline, there are two Phase III clinical products: seltorexant and aticaprant.

In the R&D pipeline update for Q3 2024, Johnson & Johnson terminated three CNS clinical research projects: the Phase II clinical study of seltorexant for Alzheimer's disease, the Phase II clinical study of a P2X7 antagonist for bipolar disorder, and the Phase I clinical study of JNJ-0376 for Parkinson's disease. This shows that even Johnson & Johnson, with its profitable products, faces challenges in CNS research and development.

In 2024, Johnson & Johnson's neuroscience business revenue reached $7.115 billion, in the innovative pharmaceuticals businessAccounting for only 12.5% in China, far lower than the 36.48% in oncology and 31.30% in immunology.

Acquiring Intra-Cellular not only boosts Johnson & Johnson's development in the neuroscience field but also includes a blockbuster drug with $5 billion in sales.

Lumateperone was first approved by the FDA in 2019 for the treatment of schizophrenia and received approval for the indication of bipolar disorder in December 2021. Supported by these two major indications,LumiparonHas already demonstrated significant commercial potential. In 2023, its sales reached $462 million, representing an 86% year-over-year increase; in 2024, growth continued, with sales in the first three quarters reaching $482 million, and full-year sales projected to reach up to $685 million.

Notably, lumateperone will continue its rapid growth. By the end of 2024, Intra-Cellular submitted a new supplemental application to the FDA for lumateperone's third indication, intended as an adjunctive treatment for Major Depressive Disorder (MDD).

The potential number of patients with MDD is much higher than those with schizophrenia and bipolar disorder. According to data disclosed by Johnson & Johnson, more than 1 billion people worldwide—1 in every 8 individuals—are affected by neuropsychiatric or neurodegenerative diseases. In the United States, approximately 2.4 million adults have schizophrenia, 6.1 million adults have bipolar disorder, and 21 million adults suffer from MDD. Therefore, Johnson & Johnson has high hopes for Caplyta, predicting its peak sales will reach $5 billion.

According to Frost & Sullivan's forecast, the global neuroscience drug market size will grow from $1.6 trillion in 2022 to $2.2 trillion in 2028. Despite the significant challenges and risks associated with CNS drug development, many pharmaceutical companies are still attracted to this field due to the high market entry barriers and enormous potential.

Technological advancements are also a key driver in the development of the CNS field. In September 2024, BMS announced that Karuna's core product, KarXT, received approval from the U.S. FDA for market launch. It is the first schizophrenia treatment with a novel mechanism approved in decades. This approval has provided BMS with a significant foothold in the fields of neuroscience and psychiatry.

Notably, Zai Lab holds the rights to KarXT in the Greater China market. According to disclosed information from Zai Lab, there are approximately 800,000 schizophrenia patients in China. Key data from the studies is expected to be obtained between 2024 and the first half of 2025, with a New Drug Application (NDA) for KarXT in the treatment of schizophrenia anticipated to be submitted in mainland China.

It is reported that, apart from treating schizophrenia, KarXT is currently undergoing registrational clinical trials to evaluate its efficacy in treating Alzheimer's psychosis, with data expected by 2026. Additionally, BMS believes KarXT has potential in other indications, including Type I bipolar disorder and Alzheimer's agitation. Analysts estimate that BMS’s KarXT, which has entered the FDA’s schizophrenia treatment process, could generate sales of up to $6 billion.

Behind KarXT, there are already nine antipsychotic drugs globally in Phase III clinical trials or the registration application stage. These include roluperidone from Mitsubishi Pharma, Lu AF35700 from Lundbeck and Enwa Pharmaceutical, sodium benzoate from SyneuRx, evenamide from Newron, and iclepertin from Boehringer Ingelheim.

In addition, Rykindo, a risperidone microsphere product independently developed by the Chinese pharmaceutical company Luye Pharma, was approved for marketing in China and the United States in 2021 and 2023, respectively. It is used to treat schizophrenia and bipolar disorder and is the first CNS new drug independently developed by a Chinese pharmaceutical company to be approved in the U.S. In the CNS field, Luye Pharma has several marketed products and R&D pipelines, demonstrating extremely strong competitiveness.