Rebooting CNS R&D: Time for Precision Neurology?

• The human brain, an organ of unparalleled complexity and the seat of our consciousness, thoughts, and emotions, remains one of the last great frontiers in medical science. Diseases of the Central Nervous System (CNS) – encompassing a vast array of neurological and psychiatric conditions such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, depression, schizophrenia, and countless rare disorders – impose an immense and growing burden on individuals, families, healthcare systems, and economies worldwide.
• The statistics are stark: nearly one in three people globally will experience a neurological disorder in their lifetime, and approximately one in eight live with a psychiatric condition. The disability-adjusted life years (DALYs) lost to these conditions run into the hundreds of millions annually, with economic costs rivaling those of cancer, cardiovascular disease, and diabetes combined

Given this profound unmet medical need, the pursuit of effective treatments for CNS disorders should, logically, be a paramount priority for the biopharmaceutical industry and its investors.

However, the landscape of CNS drug development has been characterized by a perplexing and concerning trend in recent years - Once a field bustling with research activity and attracting significant investment, the CNS therapeutic area has seemingly lost its sheen

• Major pharmaceutical companies, including pioneers in neuroscience, have been observed strategically deprioritizing their CNS portfolios, discontinuing promising, albeit high-risk, programs, and redirecting substantial resources towards other indications like oncology, immunology, and, more recently, metabolic diseases

This exodus has not gone unnoticed, raising critical questions within the scientific community, among patient advocacy groups, and in investment circles

Why is a field with such a staggering unmet need facing a decline in enthusiasm and R&D focus from some of the industry's largest players? What are the deep-seated challenges that make CNS drug development so uniquely arduous? And, most importantly, what has changed in the scientific, clinical, regulatory, and investment landscape to precipitate this shift?

The journey is undoubtedly complex, but the imperative to find solutions is undeniable        

Company Portfolio Shifts: A Move Away from CNS

Biogen: Strategic Pivot

• Despite a historical focus on neuroscience and MS, Biogen is actively "redesigning the company" with a potential migration towards immunology as well as precision neurology. This is driven by declining revenues in their traditional MS franchise and de-risking their pipeline applying resources to programs with higher perceived value and probability of success. Plans to focus on next-gen central nervous system drugs as evident by its recent partnership with an RNAi company City therapeutics

AstraZeneca: Complete Exit:

• AstraZeneca has explicitly stated it will no longer play in the neuroscience space, closing its neuroscience research group in Q1 2025. CEO Pascal Soriot noted CNS is "probably better managed by other companies that have a focus on that. Discontinued MEDI1814 (Alzheimer's) and MEDI0618 (migraine), leaving no active neuroscience programs. A Parkinson's therapy remains but is categorized under rare diseases

Broader Industry Trend (Pfizer, Amgen) etc

• Other major pharmaceutical companies have also significantly reduced or exited CNS research over the past decade. While Pfizer stopped nervous system drug discovery in early 2018, Amgen: Left the neuroscience space in 2019.

Inherent Challenges in CNS Drug Development: The "Difficult Target"

Scientific Complexity:

1. Intricate CNS Biology: The brain and spinal cord are exceptionally complex, with intricate networks, diverse cell types, and complex neurotransmitter systems. Our understanding of these systems and disease pathogenesis is often incomplete.
2. Blood-Brain Barrier (BBB): A major physiological hurdle that selectively restricts the entry of most therapeutic compounds into the brain, requiring innovative (and often complex and costly) delivery strategies.
3. Disease Heterogeneity: Many CNS disorders (e.g., Alzheimer's, Parkinson's, depression) are highly heterogeneous in their causes, manifestations, and progression, making it difficult to develop "one-size-fits-all" treatments and complicating clinical trial design.
4. Lack of Validated Biomarkers: For many CNS disorders, there's a scarcity of reliable biomarkers for early diagnosis, tracking disease progression, or measuring treatment response. This hinders efficient drug development and clinical trial conduct.

Clinical Development & Regulatory Hurdles:

1. High Attrition Rates & Low Success Rates: CNS drugs have among the lowest success rates in clinical development. Neurological drugs have a ~5.9% chance of approval from Phase 1, and psychiatric drugs ~7.3%
2. Difficult Outcome Measures: Defining and measuring clinically meaningful outcomes can be challenging. Many rely on subjective scales or complex multi-domain instruments, and translating changes in these scales to tangible patient benefit isn't always straightforward
3. Regulatory Scrutiny: Given the complexity and vulnerability of the patient populations, regulatory agencies maintain rigorous standards for safety and efficacy, which can be challenging to meet with the current scientific understanding and tools

Commercial & Investment Challenges:

1. Genericized Standard of Care: For many prevalent CNS conditions (e.g., depression, some aspects of Alzheimer's), the standard of care is dominated by older, genericized drugs. This sets a low price benchmark, making it difficult for new, innovative (and likely more expensive) drugs to gain market thereby ruling out any incentives for BioPharma to invest huge amounts of cash into neurology research
2. Securing Reimbursement: Even with approval, demonstrating sufficient value to payers (HTA bodies) is a significant hurdle, particularly when relying on novel or complex outcome measures.
3. High Financial Commitment & Risk: The combination of high R&D costs, long timelines, high failure rates, and reimbursement challenges means CNS drug development requires a very significant financial commitment and a strong appetite for risk.

Investor Sentiment and Funding Trends: What Changed?

While the user mentioned CNS was "catching up lots of investor interest in the last 10 years," the detailed data suggests a more nuanced picture, with periods of interest followed by significant pullbacks, particularly from large pharma.

1. Post-2008 Shift - Flight to "Safer Bets": The CRA Insights report notes that after the 2008 financial crisis, many large developers opted for "safer bets" over high risk CNS investments.
2. Significant Reduction in Big Pharma CNS Programs (2009-2014): The number of CNS programs in 11 large biopharma companies fell by 52% during this period.
3. Dominance of Other Therapeutic Areas (Notably Oncology): The 2010-2019 decade saw oncology dominate FDA approvals, with a 2.5x increase in the absolute number of approvals compared to the previous decade. CNS approvals, in contrast, remained relatively stagnant over the past 30 years.
4. Impact of High-Profile Failures: While not explicitly detailed in the current snippets for the last 10 years, the high attrition rates and specific major trial failures (common in areas like Alzheimer's) historically have had a chilling effect on investor sentiment and further R&D investment in those specific mechanisms or indications.

Reinventing CNS: Moving Beyond Conventional Measures

The reinvention of CNS research is not about abandoning the pursuit of therapies for diseases like Alzheimer’s, Parkinson’s, or psychiatric disorders. Instead, biopharma is shifting away from traditional approaches, such as relying solely on in-house R&D or animal models with poor predictive validity, toward more dynamic, collaborative, and technology-driven strategies. Some thoughts:

1. Decentralized and Digital Clinical Trials: The COVID-19 pandemic accelerated the adoption of decentralized clinical trials (DCTs), which reduce patient burden and improve recruitment. Bayer’s DeTAP study, published in 2021, demonstrated the effectiveness of a DCT for cardiovascular intervention in atrial fibrillation, achieving rapid recruitment and high retention rates. This approach is now being applied to CNS trials, leveraging remote patient monitoring and telemedicine to optimize data collection and patient engagement
2. AI and Digital Therapeutics: Artificial intelligence (AI) is transforming CNS research by enhancing target identification and trial design. Digital therapeutics, have been recommended for managing mental health conditions, are also gaining traction, offering non-invasive treatment options.
3. Precompetitive Consortia and Partnerships: The complexity of CNS disorders has driven biopharma to embrace collaborative models. Precompetitive consortia, involving industry, academia, and public-private partnerships, are pooling resources to develop better disease models and biomarkers. The Innovative Medicines Initiative (IMI) in Europe has connected researchers, clinicians, and regulators to tackle neurodegenerative diseases, fostering platforms for translational research. These partnerships reduce costs and risks while accelerating innovation.
4. Stratified Medicine and Biomarkers: Patient stratification, like identifying specific molecular or genetic profiles improves trial outcomes by targeting responder populations. Advances in biomarkers and genetic targets, such as those used in Alzheimer’s trials, are enabling more precise endpoints.
5. Novel Therapeutic Modalities: Gene and cell therapies are emerging as powerful tools for CNS disorders.These modalities hold promise for conditions like genetic epilepsies, where traditional drugs have failed.

Recent Advancements and Trends: The reinvention of CNS research is further evidenced by recent breakthroughs and investment trends detailed in a May 2025 Nature Biotechnology article by Melanie Senior. High-profile approvals of drugs like Bristol Myers Squibb’s Cobenfy (xanomeline and trospium chloride) for schizophrenia and Vertex Pharmaceuticals’ Journavx (suzetrigine) for pain treatment exemplify the success of new approaches. Cobenfy combines an existing muscarinic receptor agonist with a peripheral antagonist to mitigate side effects, while Journavx achieves unprecedented specificity for the Nav1.8 sodium channel, overcoming challenges that stalled earlier sodium channel blockers. These drugs represent a new generation of therapies that refine established molecules and mechanisms to address unmet needs.

Significant investments and acquisitions further underscore the field’s resurgence. Johnson & Johnson’s $14.6 billion acquisition of Intra-Cellular Therapies in 2025, which included the schizophrenia drug Caplyta (lumateperone), and Bristol Myers Squibb’s $14 billion purchase of Karuna Therapeutics in 2023 for Cobenfy highlight the value placed on innovative CNS therapies. S

Since 2020, neurology has surpassed all other indications except cancer in total M&A deal value, signaling renewed confidence in the field after years of Big Pharma retreat and while de-prioritsation of CNS by certain companies may seem counter-intuitive, industry is witnessing a sharper, focused and precision move towards developing CNS drugs.

Intelligience Opinion

The future of CNS drug development demands a bold reimagining of how the pharmaceutical industry operates. At its core must be precision medicine, a paradigm that rejects the outdated one-size-fits-all approach and instead tailors treatments to the unique biology of each patient. Central nervous system disorders—like Alzheimer’s, Parkinson’s, or depression—are not simple; they’re tangled webs of genetic, environmental, and neurological factors. Only by leveraging biomarkers and diagnostics as guiding lights can pharma unravel this complexity, enabling early detection, precise patient stratification, and real-time monitoring of treatment outcomes.

Yet, precision medicine cannot thrive in isolation. The scale of the challenge requires collaboration—not just within pharma, but across academia, biotech innovators, and even patients themselves. Silos must give way to shared purpose. This is where open-source data sharing becomes transformative. By making vast datasets accessible to all, we can accelerate discovery, eliminate redundancy, and spark innovation that no single entity could achieve alone. Imagine the possibilities: a global pool of knowledge driving breakthroughs at unprecedented speed.

The question looms large: will pharma seize this moment? The path forward is clear—integrate precision medicine, harness biomarkers and diagnostics, collaborate relentlessly, and embrace open-source data as a catalyst. But it’s not easy. It demands courage to disrupt entrenched models and a vision to see beyond short-term gains. The pioneers are already forging ahead, crafting a future where CNS therapies are as unique as the patients they serve. The rest of the industry faces a stark choice: adapt and lead, or cling to the past and fade into irrelevance.

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