The Neuroscience Breakthrough: A Century-Long Battle in a Trillion-Dollar Market

As competition in the oncology and autoimmune therapeutic tracks escalates to cutthroat levels, another "battlefield" in the pharmaceutical industry—one that bears directly on human dignity and longevity—is witnessing a grueling, almost brutal campaign for breakthroughs: the field of neuroscience.

Here lies the world's largest unmet medical need, and buried here are the "remains" of countless pharmaceutical companies: since 2003, the clinical trial failure rate for Alzheimer's disease drugs has reached as high as 99.6%—out of nearly every 100 development programs, fewer than one survives to the finish line, prompting numerous major pharmaceutical companies to successively suffer setbacks and withdraw.

This hundred-billion-yuan blue-ocean market is also widely recognized in the industry as an R&D black hole. Global pharmaceutical companies’ investments in neuroscience have likewise experienced rollercoaster-like fluctuations.

But there is one exception. Roche, the pharmaceutical giant from Basel, Switzerland, has remained in this "black hole" for nearly a century. From its foray into neuroscience in the 1920s with the launch of its first hypnotic, Apronal, to the successive market introductions of chlordiazepoxide (Librium®) and diazepam (Valium®) in the 1960s, and further to the 1973 debut of levodopa/benserazide (Madopar®), the "gold standard" for Parkinson's disease treatment, Roche has consistently remained at the forefront of the industry. Nearly a century of sustained dedication has enabled the company to accumulate profound disease insights and robust R&D capabilities, laying a solid cornerstone for subsequent breakthroughs.

Entering the 21st century, this commitment to long-termism began to bear fruit. In 2017, ocrelizumab (Ocrevus®), the world's first drug for primary progressive multiple sclerosis (PPMS), was launched, filling a clinical gap; in 2020, satralizumab (Enspryng®), a treatment for neuromyelitis optica spectrum disorder (NMOSD), entered the market and was officially approved in China the following year, ushering in a new era of precision immunotherapy for this disease. By 2025, annual sales of Ocrevus® had neared $8.5 billion, risdiplam (Evrysdi®), an oral therapy for spinal muscular atrophy (SMA), surpassed $2.1 billion, and Enspryng® sales also experienced rapid growth.

Currently, Roche has established a comprehensive presence in the fields of neuroimmune diseases, neuromuscular diseases, and neurodegenerative diseases, continuously delivering new therapeutic hope to patients with Parkinson’s disease, Alzheimer’s disease, and rare conditions such as Duchenne muscular dystrophy and Huntington’s disease.

What has truly drawn the industry’s attention is Roche’s all-in gamble in the Alzheimer’s disease field. Over two decades, billions of dollars, and multiple clinical trial setbacks—had it been any other pharmaceutical company, it would likely have long since liquidated and exited the market. Yet Roche not only refused to retreat, but successively unveiled three potential neurological blockbusters, directly targeting the toughest “bones” in this field: the blood-brain barrier and disease modification.

Recently, *Amino Observer* conducted exclusive interviews with Ms. Yijuan Chen, Vice President of Ophthalmology and Neuroscience at Roche China, and Dr. Bin Li, Vice President of Medical Affairs at Roche China, aiming to decode the breakthrough formula of this century-old pharmaceutical company.

/ 01 / The Glory and Thorns of the 100-Billion-Yuan Track

Over the past two years, the global neuroscience sector has witnessed a rare period of unprecedented prominence: Eli Lilly’s Kisunla has made a breakthrough in Alzheimer’s disease treatment, Johnson & Johnson has strengthened its central nervous system (CNS) portfolio through a landmark $13.1 billion acquisition, and AbbVie has boldly declared its ambition to become the world’s largest neuroscience company.

Behind the industry giants' intensive investments lies a set of compelling figures. The aging population is rapidly expanding the market—according to Precedence Research, the global central nervous system (CNS) drug market reached $127.29 billion in 2025 and is projected to surge to $267.62 billion by 2034.

Behind a decade of market expansion that has doubled in scale lies a stark reality: accelerating global aging is driving a year-on-year surge in patients with Alzheimer’s and Parkinson’s diseases; awareness of the diagnosis and treatment of neurological disorders such as multiple sclerosis and SMA is rapidly rising; and, more critically, most neurological conditions remain incurable and require lifelong medication, with this inelastic demand underpinning a market foundation valued at hundreds of billions.

Yet, beneath the glory lies an R&D purgatory fraught with extreme peril.

The complex pathological mechanisms of neurological diseases, the restrictive blood-brain barrier, and the scarcity of early biomarkers form a triple constraint that severely limits R&D success rates, resulting in persistently high clinical trial failure rates. Among these, Alzheimer’s disease stands as a "black hole within a black hole": by 2030, the global patient population is projected to exceed 78 million. Yet, over the past two decades, global pharmaceutical companies have invested over $100 billion, only to face successive setbacks. Aducanumab was quietly discontinued following its controversial market approval, GLP-1 receptor agonists failed to successfully expand into this indication, and antisense oligonucleotide therapies missed their primary endpoints in Phase II clinical trials, leaving countless biopharmaceutical companies to retreat in defeat.

Fields such as Parkinson's disease and multiple sclerosis are similarly mired in therapeutic challenges. Worldwide, over 10 million Parkinson's patients rely on levodopa to alleviate tremors and rigidity, yet it cannot halt disease progression, and fluctuations in therapeutic response lead to a pronounced on-off phenomenon. Among the over 2.9 million multiple sclerosis patients globally, disability continues to worsen following diagnosis. While Roche’s ocrelizumab has become the only therapy worldwide approved for both relapsing and primary progressive forms, approximately 30% of patients still lack access to more optimal treatment regimens and continue to face the burden of ongoing disease progression.

A multi-billion-dollar sector brimming with lucrative opportunities, yet fraught with challenges at every turn. After careful deliberation, most pharmaceutical companies either make a tentative foray and quickly step back, or withdraw decisively. Only a handful of true long-term players dare to stay the course against the headwinds.

“The neuroscience therapeutics sector has recently gained significant traction, but Roche is not a trend-chaser; we are long-term pioneers.” In an interview, a remark by Ms. Yijuan Chen underscored Roche’s distinctive stance in this field: “We did not enter this space simply because it is currently trending. Rather, we have been deeply engaged here for a century, with sustained investment that has yielded both breakthroughs and numerous setbacks. Neuroscience is a key strategic priority for Roche’s global end-to-end investment.” She summarized Roche’s differentiated advantages using three key terms: commitment and long-termism, a profound understanding of patients’ unmet needs, and the synergistic capabilities between pharmaceuticals and diagnostics.

This reveals Roche’s underlying logic in the neuroscience field—eschewing fleeting trends to tackle only the toughest challenges. This long-term commitment enables Roche to better understand patients’ unmet needs and emboldens it to directly confront the two core bottlenecks in the industry.

/ 02 / The Smart Key to Unlocking the Blood-Brain Barrier

As the human body's most sophisticated defense system, the blood-brain barrier serves as a natural shield for the brain, yet it remains the foremost challenge in neurological drug development.

“The core pathology of Alzheimer’s disease involves the abnormal deposition of β-amyloid in the brain, forming plaques that damage neurons and ultimately lead to cognitive decline. The greatest bottleneck for previous large-molecule antibody drugs has been the blood-brain barrier; the vast majority of these macromolecules cannot cross it, resulting in extremely low intracerebral concentrations and inherently limited therapeutic efficacy,” Dr. Bin Li stated directly. “This barrier has constrained countless pharmaceutical companies.”

The blood-brain barrier penetration rate of conventional antibodies is less than 0.1%, meaning that even with a perfectly designed target, if the drug cannot enter the brain, all other efforts are ultimately futile.

The key to breaking the bottleneck undoubtedly lies in more efficient and safer brain delivery technologies. Roche has developed the Brainshuttle™ technology, which Dr. Li Bin described as follows: "It functions like a 'smart key' specifically designed to cross the blood-brain barrier—after the drug binds to the transferrin receptor, it utilizes the body's own endocytic transport mechanism to be 'internalized' into the brain, thereby achieving active transport across the blood-brain barrier." The data is striking: this technology can increase the brain delivery efficiency of drugs by tens of times, clearing over 90% of amyloid plaques within a short period.

Leveraging this technology, Trontinemab, Roche’s core pipeline candidate for Alzheimer’s disease, achieves high drug exposure at lower doses, thereby enabling rapid and profound amyloid clearance. Previously published Phase Ib/IIa data for Trontinemab demonstrated that 91% of patients in the high-dose cohort achieved amyloid negativity in the brain within 7 months, of whom 37 patients (72%) achieved deep clearance, with clearance speed and efficacy far surpassing existing therapies. More importantly, the incidence of amyloid-related imaging abnormalities (ARIA) was significantly reduced, remaining at an exceptionally low rate of less than 5%.

What does this figure signify? Although the Alzheimer’s disease antibody drugs approved over the past two years can also clear plaques, they require high-dose administration, which carries a significant risk of adverse effects—specifically, a higher incidence of ARIA, with patients potentially developing cerebral edema or microhemorrhages.

This means that future competition for Alzheimer's disease drugs will no longer be solely a battle over targets, but rather a comprehensive contest encompassing delivery efficiency, therapeutic efficacy, and safety.

Currently, Roche has initiated a Phase III clinical trial program for Trontinemab, alongside plans to explore prophylactic dosing in patients at the preclinical stage. The earlier the clearance of pathological waste from the patient's brain, the wider the window of opportunity for reversing neurological damage.

Although this preventive research remains in its early stages, for a disease that has discouraged the entire industry for decades, this exploration itself represents a rare hope.

Beyond therapeutic drugs, Roche has also achieved a breakthrough in diagnostics: historically, Alzheimer’s disease diagnosis relied heavily on invasive cerebrospinal fluid (CSF) puncture, which was costly and difficult to widely implement. Today, Roche’s pTau181 and pTau217 blood biomarker assays enable early screening and precise diagnosis via peripheral blood, lowering the screening threshold and facilitating widespread early diagnosis.

As Dr. Li Bin stated, Roche's unwavering commitment to Alzheimer's disease has spanned over two decades and involved billions of dollars in investment. Despite multiple setbacks, the company has never ceased its pursuit of breakthroughs across both therapeutics and diagnostics to benefit patients.

/ 03 / From Treating Symptoms to Addressing the Root Cause

For patients with neurological disorders, the cruelest reality is not the current symptoms, but the despair of a relentlessly deteriorating condition.

In the field of Parkinson's disease, levodopa remains the cornerstone of clinical therapy to date. However, it only provides temporary symptomatic relief, cannot halt the progressive degeneration of dopaminergic neurons, and is associated with a pronounced "on-off phenomenon." Likewise, medications for Alzheimer's disease are unable to reverse neuronal damage. As Professor Chen Biao of Xuanwu Hospital, Capital Medical University, stated: "What patients desire most is a cure. Currently, however, age-related neurodegenerative diseases cannot be cured. Only disease-modifying therapies that can delay or even halt disease progression represent the true path forward at this stage."

“Alzheimer’s disease and Parkinson’s disease do not develop suddenly; there is already a 15- to 20-year pathological latent period before obvious symptoms such as tremor, bradykinesia, rigidity, and memory decline appear,” Professor Chen Biao stated. He emphasized that the core objective in current clinical practice is to delay the age of onset, ideally from 60 to 80 years, so as to prevent severe disability during the patient’s lifetime and maintain their quality of life.

This is the significance of so-called disease modification, and it also represents a major "holy grail" in the field of neuroscience.

“Rather than merely treating the symptoms, it is far better to address the root cause.” Dr. Li Bin hit the mark. Roche’s strategic approach has long moved beyond the superficial logic of symptomatic relief, directly targeting the root causes of disease and advancing disease-modifying therapies through multiple pathways.

In the field of Parkinson’s disease, Roche’s core pipeline candidate prasinezumab targets abnormally aggregated α-synuclein, the pathogenic protein aggregates responsible for the disease. Phase IIb data demonstrate that the drug can slow the progression of motor decline by 30%–40% in early-stage patients. By blocking the spread of these toxic aggregates at the source and delaying disease worsening, prasinezumab has entered Phase III clinical trials and is poised to end the historical era of purely symptomatic treatment for Parkinson’s disease. Two deeper therapeutic strategies are also underway: intervention for lysosomal dysfunction to help “upgrade and reboot” the neurons’ intrinsic waste-clearance system, and modulation of neuroinflammation to precisely curb chronic neuronal damage.

In the field of multiple sclerosis, Roche’s fenebrutinib is charting a new course: an oral BTK inhibitor capable of crossing the blood-brain barrier, simultaneously targeting peripheral B cells and central microglia. This dual-targeting approach addresses both the peripheral and central axes of the disease—inhibiting peripheral immune attacks while alleviating central neuroinflammation, thereby blocking chronic neurological damage at its source. Phase III data demonstrate that fenebrutinib reduces the annualized relapse rate in patients with relapsing multiple sclerosis by more than 50%, meaning patients experience a relapse on average only once every 16 years. Such efficacy is a true embodiment of a "root-cause addressing" strategy.

In the arena of neuroscience, many hard-fought battles still lie ahead. Yet Roche remains steadfast in its original mission, consistently dedicating its unwavering resolve and perseverance to tackling the most challenging and complex therapeutic frontiers.

/ 04 / Closed-Loop Ecosystem, Safeguarding Tens of Millions of Patients

In addition to the three high-potential drugs mentioned earlier—Trontinemab, Prasinezumab, and Fenebrutinib—Roche’s marketed products also stand as benchmarks. Satralizumab (Enspryng®), a therapy for neuromyelitis optica spectrum disorder (NMOSD), is the world’s first and only approved subcutaneous treatment for NMOSD, significantly enhancing patient treatment satisfaction. Meanwhile, clinical research for indications such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and autoimmune encephalitis is being accelerated, with the potential to fill further therapeutic gaps. Ocrelizumab (Ocrevus®), a multiple sclerosis therapy, requires only two subcutaneous injections per year, each lasting just ten minutes; it achieved sales of $8.474 billion in 2025, substantially improving patient adherence. Risdiplam (Evrysdi®), the world’s first oral treatment for spinal muscular atrophy (SMA), overcomes the limitations of intrathecal administration. With 2025 sales reaching $2.124 billion, it frees patients from the burden of frequent injections.

It is evident that Roche's neurological disease pipeline rejects a “broad but shallow” approach, adhering instead to a “focused and comprehensive” strategy. Ms. Chen Yijuan emphasized that over a century of dedicated expertise has enabled Roche to deeply understand patient needs, enhancing patient adherence through strategies such as oral formulations and extended dosing intervals, while also maintaining a profound understanding of the most urgent and unmet clinical needs within the field of neuroscience.

Unlike most pharmaceutical companies that focus primarily on drug R&D, Roche’s ambition has never been confined to merely “developing a good drug.” Instead, with pharmaceuticals at its core, it aims to build a fully integrated, end-to-end ecosystem that rapidly translates innovative drugs from the laboratory to clinical practice, ensuring they truly benefit patients; simultaneously, it synergizes with its diagnostics business to facilitate early screening, thereby further amplifying therapeutic value.

Ms. Chen Yijuan pointed out that China is a core strategic market for Roche globally. Roche’s localization strategy is not merely about introducing drugs to the market, but rather about embedding the entire value chain in China, encompassing early-stage R&D, clinical development, manufacturing, commercialization, and local innovation partnerships.

In terms of product introduction, Roche is accelerating the launch of global innovative drugs in China to benefit Chinese patients. Currently, multiple drugs for Parkinson’s disease, spinal muscular atrophy, neuromyelitis optica, and multiple sclerosis have been launched in China; regarding medication access, facilitating the inclusion of innovative drugs in the medical insurance system is a key step to alleviate patients' financial burden.

Currently, multiple of Roche's drugs for neurological disorders have been included in the National Reimbursement Drug List, resulting in a substantial decrease in patients' annual treatment costs and significantly improved accessibility. Concurrently, within the framework of national policies, Roche is assisting economically disadvantaged families through charity initiatives and patient support programs to alleviate their medication burden.

More importantly, neurological disorders often require lifelong medication. For instance, the treatment duration for Parkinson’s disease patients from diagnosis to the advanced stage may exceed 20 years. Given the patients' advanced age and limited mobility, prescription renewal at the primary care level poses a significant challenge.

Roche's solution focuses on supporting the development of an integrated, vertically coordinated diagnosis and treatment system. By establishing treatment protocols at top-tier clinical hospitals and connecting them with primary care facilities through healthcare consortiums, Roche has implemented pathways that enable patients to conveniently access local follow-up visits and prescription renewals, seamlessly linking the entire care continuum from initial consultation and prescription renewal to home-based rehabilitation. Additionally, Roche leverages large language models (LLMs) and AI agents to develop a long-term management tool for chronic neurological conditions, assisting physicians with follow-up care, home-based support, and dynamic monitoring of patients' conditions.

“We do not merely develop pharmaceuticals; what we strive for is to leverage the power of a systematic approach to ensure patients achieve sustained benefits from whole-course disease management,” said Ms. Chen Yijuan.

Meanwhile, in terms of production layout, Roche also stated that it will continue to advance the localized manufacturing of innovative drugs to ensure supply and reduce costs; in terms of innovative collaboration, it will partner with cutting-edge enterprises in China and its headquarters' R&D teams to jointly explore the application of brain-computer interfaces and AI-driven drug discovery in the field of neurological diseases, and support local startups through the "Roche China Innovation Accelerator" to jointly pursue breakthroughs in global neuroscience.

This localized ecosystem transforms Roche's innovations into a readily accessible treatment hope for patients in China, while also ushering neurological diseases into a new stage of predictability, early screening, intervention, and management. The significance of this for both patients and the healthcare system is self-evident.

/ 05 / Summary

Breakthroughs in overcoming the blood-brain barrier, the implementation of disease-modifying therapies, and the optimization of early diagnosis and treatment systems—these challenges will not be resolved overnight, but from early exploration to technological breakthroughs, and from pipeline advancement to ecosystem development, Roche is providing a new possibility for the field of neuroscience, opening a new door.

Behind this door lies both the hope for an industry transitioning from an R&D black hole into a new era, and the long-awaited tomorrow for hundreds of millions of patients.

       Original Title: The Critical Battle in Neuroscience, The Past and New Landscape of a Hundred-Billion Market