CNS Sector Explodes: Two Deals Exceeding $2 Billion Each Closed in a Single Day

On May 13 local time, two blockbuster deals exceeding $2 billion each occurred in the CNS field.

First, Takeda announced that it has entered into a global exclusive option and license agreement with AC Immune for the Aβ-targeting vaccine product ACI-24.060, valued at up to $2.2 billion.Under the terms of the agreement, AC Immune will receive a $100 million upfront payment and will be eligible for additional potential development, commercialization, and sales milestone payments totaling up to approximately $2.1 billion if all relevant milestones are achieved during the term of the agreement. Following product commercialization, AC Immune will be entitled to tiered, double-digit royalties on global net sales.

Second, AbbVie and Gilgamesh announced a collaboration and option agreement worth over $2 billion to develop next-generation therapies for mental disorders.Under the terms of the agreement, AbbVie and Gilgamesh will jointly research and develop a next-generation portfolio of therapies for psychiatric disorders. Upon exercise of the option, AbbVie will lead development and commercialization activities. Gilgamesh will receive a $65 million upfront payment from AbbVie and will be eligible for up to $1.95 billion in option fees and milestone payments, as well as tiered royalties on net sales ranging from the mid-single digits to the low double digits.

In the 21st century, the U.S. National Institutes of Health (NIH) has invested more than $8 billion in neuroscience research, nearly ten times the amount spent in the 1990s. Alzheimer’s disease (AD) has become the third disease area to receive dedicated priority funding from the NIH, following cancer and HIV/AIDS.

Massive investments correspond to the vast, unmet needs of patients. According to WHO projections, central nervous system (CNS) diseases will become the second leading cause of death within the next 20 years. Data released by the U.S. National Institutes of Health indicate that the prevalence rates of depression and severe mental illness in the United States have reached relatively high levels of 7% and 4%, respectively, with an overall trend of continuously rising incidence and onset at younger ages. The number of Alzheimer’s disease (AD) cases is also on the rise; it is estimated that 50 million people worldwide are living with AD and other forms of dementia. This figure is projected to increase to 82 million by 2030 and to over 100 million by 2050.

In China, one in six people suffers from neurological disorders. Population aging has led to a year-on-year rise in neurodegenerative diseases; it is reported that there are over 2.5 million Parkinson’s disease patients and nearly 10 million Alzheimer’s disease patients in China. However, for central nervous system (CNS) disorders such as schizophrenia, addiction, depression, and Alzheimer’s disease (AD), the efficacy of existing treatments is less than 50%, indicating substantial unmet clinical needs and significant market potential.

According to Frost & Sullivan statistics, the global market size for central nervous system (CNS) drugs was $124.5 billion in 2019, making it the fourth-largest pharmaceutical market. Over the next 15 years, the global CNS drug market is projected to maintain steady growth, reaching $172.1 billion by 2034. In 2019, the market size for CNS drugs in China was $29.6 billion. Over the next 15 years, China’s CNS drug market is expected to achieve rapid growth, reaching $57.1 billion by 2034. Based on China’s pharmaceutical sales revenue in 2019, the therapeutic area for central nervous system disorders accounted for 12.5% of the total pharmaceutical market share that year.

Although scientific research on the human brain has a history spanning several centuries, constrained by limitations in science and technology, significant breakthroughs have only been achieved in the past two decades. Nevertheless, with billions to tens of billions of neurons in the brain that form neural networks through interactions to mediate signal transmission, our understanding of the human brain remains less than 10% of its total structure and function.

Given the complexity of the central nervous system (CNS) and the challenges inherent in drug development, there remains a substantial unmet clinical need for pharmacological treatments for many CNS disorders, such as stroke, substance use disorder, major depressive disorder, schizophrenia, and Alzheimer’s disease. The vast market potential for these conditions is evident. With the continuous advancement of sophisticated instrumentation, the industry now has the capability to study individual neurons and synapses, bringing basic research to a critical threshold for breakthroughs.

Therefore, it is anticipated that over the next 5–10 years, a greater number of central nervous system (CNS) disorders will become amenable to effective pharmacological treatment. Within the industry, whichever entity first identifies a breakthrough point will achieve a milestone advancement in the field and rapidly capture the blue ocean market for specific niche diseases.

Major pharmaceutical companies and multinational corporations (MNCs) have always been highly attuned to opportunities in blue-ocean markets. In recent years, numerous MNCs and global pharmaceutical firms—including GSK, AbbVie, Takeda, Novartis, Roche, Sumitomo, and Merck & Co.—have aggressively expanded their presence in the central nervous system (CNS) therapeutic area.The two collaborations introduced at the beginning of this article also fall within this niche sector.

According to Takeda’s press release, ACI-24.060 is an active Aβ immunotherapy candidate designed to elicit polyclonal antibody responses against Aβ oligomers and pyroglutamate Aβ. For many years, the development of Alzheimer’s disease (AD) therapeutics has primarily focused on two targets: amyloid-beta (Aβ) protein and tau protein.ACI-24.060 has the potential to delay or slow the progression of Alzheimer’s disease by inducing plaque clearance and effectively inhibiting plaque formation in the brain.

Currently, ACI-24.060 is undergoing the ABATE randomized, double-blind, placebo-controlled Phase 1b/2 trial,to evaluate the safety, tolerability, immunogenicity, and pharmacodynamic effects of an investigational immunotherapy in patients with prodromal Alzheimer’s disease and adults with Down syndrome. AC Immune expects to announce partial Phase 2 results from the ABATE trial in the second quarter of 2024, and Aβ PET imaging data after 12 months of patient treatment in the fourth quarter of 2024.In addition, AC Immune also expects to announce preliminary safety and immunogenicity data for ACI-24.060 in the cohort of patients with Down syndrome in the second half of 2024.

AbbVie’s announcement indicates that the collaboration will leverage AbbVie’s expertise in psychiatry and Gilgamesh’s innovative research platform toDiscovery of novel neuroblasts to jointly research and develop next-generation drug combinations for the treatment of mental disorders.The announcement also indicates that classic psychedelic compounds offer novel mechanisms for addressing mental health disorders, with some demonstrating favorable clinical efficacy in cases where other treatments have failed. However, these first-generation compounds may induce severe psychoactive side effects, such as hallucinations.

Gilgamesh’s nerve growth factor is designed to target mechanisms that deliver significant clinical efficacy, thereby minimizing the side effects associated with first-generation psychedelic compounds. These novel compounds hold great promise for treating a variety of psychiatric disorders, including mood and anxiety disorders.

In fact, this marks AbbVie’s second major investment in the CNS sector within the past six months.

In December 2023, AbbVie acquired Cerevel and its neuroscience product pipeline for $8.7 billion., strengthening the former's footprint in neuroscience. Cerevel’s pipeline comprises multiple clinical-stage and preclinical candidate drugs developed for the treatment of conditions such as schizophrenia, Parkinson’s disease (PD), and mood disorders, with its core asset being the M4 receptor candidate Emraclindine, which is designed to treat negative symptoms of schizophrenia and improve cognitive function.

In the same month, BMS acquired Karuna at a 53.35% premium per share, with a total transaction value of approximately $14 billion., acquiring the latter's schizophrenia drug KarXT. Some institutions predict that KarXT's potential peak sales could reach as high as $6 billion.

In addition, a social anxiety disorder (SAD) medication named Fasedienol (PH94B) also “broke into the mainstream” in 2023. This was because Vistagen, the company developing the product, announced that its Phase 3 PALISADE-2 clinical study of Fasedienol nasal spray for the treatment of social anxiety disorder had achieved positive top-line results. The data released represented the “first positive Phase 3 study” for SAD therapies in the United States in 15 years, causing the company’s stock price to surge for several consecutive days last August.

Multiple pharmaceutical companies have concurrently intensified their efforts in the same therapeutic area, primarily due to stagnant financial performance. The expiration of patents and the continuous emergence of novel products have caused growth to decelerate for formerly core offerings, prompting companies to seek breakthroughs beyond their traditional areas of strength. AbbVie’s CEO previously stated at an investor conference that the acquisition of Cerevel was strategically oriented toward the future, with the resulting performance implications being more relevant to the next decade.

Despite the intense competition in the field, the industry has yet to see a “blockbuster product.” Instead, much of the news highlights major companies’ failures in the CNS therapeutic area, with Alzheimer’s disease (AD) once becoming a “black hole” for new drug development.

Currently, the development of central nervous system (CNS) drugs remains challenging, characterized by high costs, lengthy clinical translation pathways, and high failure rates. Specifically, CNS drug development faces various challenges, including difficulties in developing preclinical models of diseases, the need for drugs to cross the blood-brain barrier (BBB), limited understanding of relevant pathophysiology, difficulties in assessing target engagement, heterogeneity of clinical phenotypes, limited understanding of the heterogeneity of neurobiological phenotypes, and a lack of sensitivity in clinical rating scales.

Addressing physiological barriers, particularly the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier, achieving sufficient delivery across the BBB remains a key challenge in the development of central nervous system (CNS) drugs.With the continuous in-depth research into the structure and mechanisms of the blood-brain barrier (BBB) by the industry, and the rapid development of delivery technologies represented by materials science and nanotechnology, various BBB modulation and crossing strategies have been developed. Engineered delivery systems with unique physicochemical properties and multifunctional motifs have been prepared to enhance drug delivery through different BBB crossing pathways.

On the other hand, drug development for CNS sub-specialties such as Alzheimer’s disease (AD) has long revolved around the unproven “amyloid-beta hypothesis.” However, any therapeutic approach that has not yet achieved successful commercialization—and thus lacks robust market validation—can still be regarded as a “hypothesis.” As such, hypotheses require multifaceted validation. Typically, when one hypothesis fails to be validated, new data generated from the failure inform the formulation of an alternative hypothesis for further testing.In light of the unclear mechanisms underlying certain CNS diseases, industry professionals should adopt a broader and alternative perspective to determine whether these challenges can be comprehensively addressed through multi-mechanistic and multi-pathway approaches.

Furthermore, to counter the high R&D risks and slow progress associated with CNS drugs, some companies choose to pursue innovative breakthroughs on established targets or adopt drug repurposing strategies to accelerate development timelines and mitigate pipeline risks.

CNS, the crown jewel of brain science and the final frontier in humanity’s exploration of nature, is on the verge of an explosive breakthrough, driven by years of accumulated progress in basic research and industrial translation. As the fog surrounding commercialization clears, hundreds of millions of patients worldwide can look forward to the dawn of a cure.