Divergent CNS Strategies: Johnson & Johnson's Bold Acquisition vs. AbbVie's Cautious Reassessment
Johnson & Johnson
Medical Device R&D and Manufacturer
Amino Observation - Original Production by the Innovative Drug Team
Author | Cai Jiu
Another pharmaceutical company has stumbled in the field of schizophrenia treatment.
On January 16, Boehringer Ingelheim announced the primary results of the Phase 3 clinical program CONNEX for iclepertin in treating cognitive impairment in adults with schizophrenia. Both the primary endpoint and key secondary endpoints of the program did not meet expectations. Based on this, Boehringer Ingelheim decided to immediately terminate the long-term extension trial CONNEX-X.
This is the second giant pharmaceutical company to stumble in the schizophrenia field recently. Not long ago, "ace project" emraclidine, which AbbVie acquired from Cerevel, failed to meet the expected endpoints in two Phase II studies targeting schizophrenia.
This lesson has forced AbbVie to reassess its investment strategy in the field of central nervous system diseases. At the 2025 JPM conference, AbbVie revealed: "When it comes to investing heavily in early-stage data research in the future, we will definitely reconsider our approach."
However, in the CNS field, pharmaceutical companies have polarized attitudes. Some are more cautious, while others are still aggressively advancing.
On the first day of the 2025 JPM conference, Johnson & Johnson took center stage as it announced a $14.6 billion acquisition of Intra-Cellular, a company focused on the CNS field, aiming to obtain its blockbuster antipsychotic drug Caplyta.
Once the acquisition is successful, it will surpass the acquisitions of Karuna and Cerevel to become the largest M&A deal in the CNS field since 2023.
The huge difference in attitude also reflects that multinational pharmaceutical companies have already had obvious disagreements in the CNS field.
/ 01 /
A More Cautious AbbVie
It is understandable that AbbVie has become more cautious, as the acquisition of Cerevel has cost it dearly.
At the end of 2023, AbbVie announced an $8.7 billion acquisition of Cerevel, whose core pipeline is Emraclidine, a selective positive allosteric modulator of the muscarinic receptor M4, a potential breakthrough candidate in the field of schizophrenia.
The large patient population and the urgent need for new therapies have made schizophrenia a goldmine for big pharmaceutical companies, and AbbVie also hopes to make achievements. Emraclidine might help AbbVie realize this aspiration.
Based on the results from Part B of the Phase 1b trial, 52 patients with schizophrenia showed overall good tolerability, with no serious treatment-related adverse events or participant discontinuations due to treatment. As a result, Cerevel gained the favor of AbbVie and was eventually acquired at a high premium.
However, the results were disappointing. As mentioned above, two Phase II studies for schizophrenia failed to meet their primary endpoints. Emraclidine’s performance was far less impressive compared to the Phase 1b trial results published by Cerevel, leaving AbbVie in a difficult position. Last week, AbbVie recorded an impairment charge of approximately $3.5 billion to reflect the impact of emraclidine's clinical setback on its books.
However, the loss of this gamble was due to both natural disasters and man-made factors. From the first acquisition offer to the final takeover of Cerevel, AbbVie only took less than two months, making it hard to judge whether it was decisiveness or rashness.
The impulsive decision came at a cost. AbbVie must necessarily rethink its investment in neuropsychiatry.
Therefore, at the 2025 JPM conference, although AbbVie executives expressed that the company is still willing to take "calculated risks," they also made it clear that significant investments in early-stage CNS assets will be approached with greater caution.
/ 02 /
Johnson & Johnson's Major Offensive
Johnson & Johnson's optimism is not surprising.
As an innovative pharmaceutical company focused on CNS drug development, Intra-Cellular's core asset currently is Caplyta, an oral antipsychotic taken once daily.
This is a 5-hydroxytryptamine 2A (5-HT2A) receptor antagonist and dopamine receptor D2 modulator, originally developed by Bristol-Myers Squibb. In 2015, Intra-Cellular acquired the license for global development.
From a mechanistic perspective, lumateperone partially agonizes dopamine D1 and D2 receptors, antagonizes 5-HT2A receptors, inhibits DA and 5-HT transporters, and promotes the activation of the NR2B subunit of NMDA receptors. Therefore, Caplyta has demonstrated therapeutic potential in various CNS disorders.
In December 2019, Caplyta was approved by the FDA for the treatment of adults with schizophrenia, and in December 2021, it was also approved as an adjunctive treatment for depressive episodes associated with bipolar I or II disorder (bipolar depression).
Supported by these two major indications, Caplyta has 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.
As expected, Caplyta will continue to grow rapidly. Just at the end of last year, Intra-Cellular submitted a new application to the FDA for the third indication of Caplyta, as an adjunctive treatment for major depressive disorder (MDD), which is a broader indication.
In the United States, approximately 2.4 million adults have schizophrenia, 6.1 million adults have bipolar disorder, and 21 million adults have MDD.
According to Johnson & Johnson, if approved, Caplyta is expected to become the first drug in 15 years to be approved for treating MDD and depressive symptoms of bipolar I and II disorders. Therefore, in Johnson & Johnson's view, Caplyta's peak sales are projected to reach $5 billion.
For Johnson & Johnson, acquiring a blockbuster with a peak of $5 billion not only strengthens its CNS portfolio but also provides more confidence in facing the upcoming patent cliff.
/ 03 /
Persistent Disagreements
AbbVie and Johnson & Johnson, one on the left and the other on the right, reflect the "divergence" that may continue to exist in the CNS field: cautious people exist, and optimistic people will not disappear.
The optimism lies in the vast opportunities in the CNS field. CNS diseases are recognized as one of the areas with the lowest contribution of drug treatments and the highest unmet clinical needs. According to WHO predictions, within 20 years, CNS diseases will become the second leading cause of death.
The number of patients with most central nervous system (CNS) diseases is no less than those with tumors and cardiovascular diseases, indicating a sufficiently large pharmaceutical market. Moreover, the clinical effectiveness for most CNS diseases remains inadequate, reflecting a significant amount of unmet clinical needs.
Therefore, the CNS field is bound to attract the entry of many pharmaceutical companies.
But caution will not disappear.
Although the prospect of CNS field is tempting, the difficulty of success can be described as hell mode: data shows that the R&D success rate of central nervous system drugs is only 6%, less than half of the success rate of other drug R&D.
The core reason lies in the fact that every step, from unclear mechanisms to the difficulty in validating animal models and the high complexity of clinical development, poses a major hurdle for CNS drug development.
Taking medications for negative symptoms of schizophrenia as an example, there are currently no drugs approved globally for the treatment of negative symptoms of schizophrenia due to two reasons:
First, the mechanism is not clear. Schizophrenia is an extremely complex group of diseases, and currently, the pathogenic mechanisms of patients with positive and negative symptoms are different.
For example, the most widely accepted dopamine hypothesis suggests that positive symptoms result from hyperactive dopaminergic neurotransmission in the limbic pathways, while negative symptoms, loss of motivation, and cognitive impairments are considered to be caused by hypodopaminergic function in the frontal lobe and other mesolimbic structures. The pathogenic mechanism remains unclear, posing significant challenges for the development of symptomatic drugs.
Second, the clinical development is extremely challenging. Due to the subtle nature of negative symptoms in schizophrenia, along with the diversity of symptoms and other factors, the clinical development for this disease is exceptionally difficult. For instance, the significant heterogeneity among patients makes it hard to effectively evaluate the final outcomes; additionally, the onset of the disease may not be continuous but rather occur at specific intervals, which also makes it difficult to assess the long-term efficacy of drugs.
Various factors have led to the burial of many ideal-filled prospectors in the drug development for negative symptoms of schizophrenia. This, in fact, serves as a microcosm of CNS field research and development.
So, whether to safeguard existing achievements while proceeding steadily or to forge new territories through bold breakthroughs, the choice in the CNS field reflects a company’s profound understanding of the value of pharmaceutical innovation and, more importantly, its current risk assessment.
The objectively existing reality has predetermined that "divergence" is bound to persist.
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