For decades, neuroscience drug development struggled with low success rates.¹ Many major pharmaceutical companies scaled back or closed their CNS research divisions during the 2000s and 2010s after repeated failures. Most approved drugs during that time provided only symptomatic relief, such as cholinesterase inhibitors for Alzheimer’s disease, without addressing the underlying cause.
Today, that landscape is changing dramatically. Advances in understanding the biology of brain disorders, spanning genetics, protein aggregation, and neuroinflammation, combined with powerful biomarkers, imaging technologies, AI-driven discovery platforms, and more supportive regulatory pathways, have transformed the field. Analysts now describe this shift as a genuine “return to neuroscience,” driven by the arrival of disease-modifying therapies and smarter, more targeted clinical development strategies.
The Turning Point: Why Pharma Is Returning to Neuroscience
After years of limited progress, neuroscience research has entered a period of rapid advancement. A combination of scientific breakthroughs, digital innovation, and regulatory support is transforming how pharmaceutical companies approach brain disorders, making the once high-risk CNS field attractive again.
Improved biological insights: Alzheimer’s genetics, such as APOE and TREM2, have revealed links between amyloid and tau pathology and the immune system. Neuroinflammation is now recognized as closely connected to the buildup of abnormal proteins in the brain. In depression, research on brain circuitry and synaptic plasticity has expanded beyond serotonin signaling, providing clearer molecular targets, including microglia, tau, and synaptic proteins.
Advanced biomarkers and imaging: Blood tests that measure amyloid and phosphorylated tau can now detect Alzheimer’s pathology with high accuracy. In 2025, the FDA approved the first plasma pTau217/Aβ42 ratio test.² Amyloid and tau PET imaging techniques have improved early diagnosis and patient selection. Reviews note that biomarkers were crucial for recent Alzheimer’s drug approvals by confirming target engagement and plaque removal. Digital tools such as mobile applications, wearable devices, and EEG headbands are also being used to monitor mood and cognition with high frequency.³
AI, genomics, and big data: Machine learning is increasingly used to analyze genomic and proteomic data, identify novel drug targets, repurpose existing compounds, and optimize trial design. Insilico Medicine reported that by integrating AI, it shortened the process of identifying a lead compound to about 12–18 months instead of the traditional 2.5–4 years.⁴ Similarly, BioXcel Therapeutics’ NovareAI platform uses big-data analytics to repurpose previously shelved CNS candidates.⁵
Regulatory support: The FDA has adopted accelerated and breakthrough pathways to encourage innovation in CNS drug development. Lecanemab (Leqembi) received accelerated approval in January 2023 and was granted full approval in July 2023 following confirmatory trial results.⁶ Esketa mine was granted Breakthrough Therapy designation and received approval for treatment-resistant depression in 2019 in combination with an oral antidepressant, and later as a standalone therapy.⁷
These scientific, technological, and regulatory advances have reshaped the industry’s view of neuroscience R&D. Pharma companies now see realistic opportunities to develop treatments that can modify disease progression in Alzheimer’s, depression, and other brain disorders. Together, these advances are redefining neuroscience R&D and restoring confidence in an area once considered too risky for major investment.
Breakthroughs in Alzheimer’s Disease
Alzheimer’s research is now at a crucial breakthrough point. Newly approved therapies that address the disease’s root causes have transformed the focus from easing symptoms to actually modifying how the disease progresses.
From Symptom Control to Disease Modification: Older medications such as donepezil, rivastigmine, and memantine provided modest symptomatic relief but did not slow or halt disease progression. The development of new monoclonal antibodies that target the underlying amyloid pathology has demonstrated measurable clinical benefits, validating amyloid-directed therapeutic strategies in patients.
FDA-Approved and Late-Stage Therapies:
Aducanumab (Aduhelm, Biogen/Eisai). Received accelerated approval in June 2021 based on its ability to reduce amyloid plaques. Although controversial, it established proof of concept that amyloid plaques can be cleared from the brain.
Lecanemab (Leqembi, Eisai/Biogen). Gained accelerated approval in January 2023, followed by full approval in July 2023 after confirmatory results from the CLARITY-AD trial. The study showed that lecanemab slowed cognitive and functional decline by approximately 27% on the CDR-SB scale at 18 months.⁸
Donanemab (Kisunla, Eli Lilly). Received full approval in July 2024 for early Alzheimer’s disease, demonstrating strong amyloid clearance and significant slowing of decline on both the iADRS and CDR-SB scales. Greater plaque removal was associated with reduced tau accumulation and slower clinical deterioration. Approximately 75% of treated patients reached “amyloid not elevated” status within 18 months of therapy.⁹
These landmark approvals have revitalized neuroscience pipelines across the pharmaceutical industry. Roche currently leads with over 20 CNS projects, while AbbVie manages approximately 16. Established leaders such as Biogen and Lundbeck continue to invest heavily in neurodegenerative research, and former retreaters like Novartis and Sanofi are now re-entering the field with renewed confidence.
Beyond Amyloid: Next-Wave Approaches
With the success of amyloid therapies, researchers are turning their attention to other biological drivers of Alzheimer’s disease. The focus is shifting toward complementary and potentially more comprehensive strategies that target tau pathology, neuroinflammation, metabolic dysfunction, and genetic risk factors. These next-generation approaches aim not only to enhance the effects of amyloid removal but also to address the broader mechanisms that contribute to disease progression.
● Tau-directed therapies: New treatments are being designed to prevent or clear abnormal tau buildup, which spreads through the brain as the disease advances. These include antisense oligonucleotides targeting the MAPT gene and tau-specific immunotherapies intended to block tau aggregation and propagation.
● Neuroinflammation modulators: Researchers are developing compounds that modulate the brain’s immune response. Promising targets include TREM2 agonists that enhance microglial function, NLRP3 inflammasome inhibitors, and cytokine blockers that reduce damaging inflammatory signaling.
● Neuroprotection and metabolism: Several experimental approaches aim to strengthen neuron survival and brain energy balance. These include BDNF mimetics that support synaptic health, metabolic modulators that optimize cellular energy use, and emerging gene therapies for familial Alzheimer’s disease caused by known mutations.
● Precision diagnostics: Advanced plasma biomarkers and neuroimaging tools are helping identify patients most likely to benefit from specific therapies. This precision-medicine approach is paving the way for individualized treatment strategies tailored to the underlying biology of each patient’s disease.
Rethinking Depression: From Serotonin to Synaptic Rewiring
Depression research is shifting from targeting serotonin to repairing brain connections and enhancing neuroplasticity. New research focuses on how the brain’s connections and signaling can be repaired to bring faster and longer-lasting relief.
Ketam ine and Esketa mine: The Glutamate Pathway.
Esketa mine, a type of keta mine, works on the brain’s glutamate system instead of serotonin. It helps rebuild synaptic connections and can improve mood within 24 hours, even in people with suicidal thoughts. It is given as a nasal spray under medical supervision through a REMS program.¹º
Psychedelic-Assisted Therapies.
Medicines like psilocybin (COMP360) and MDMA are being tested for people who do not respond to standard antidepressants. Psilocybin has shown clear benefits in treatment-resistant depression, and MDMA therapy has greatly reduced PTSD symptoms. Both have received FDA Breakthrough Therapy designations for their potential.¹¹
Precision Psychiatry and Digital Biomarkers.
Technology is helping doctors personalize treatment. EEG and brain scans (fMRI) can show who is likely to respond to certain drugs, while smartphones and wearables can track speech, sleep, and activity changes. Studies show that daily tracking through wearables can reliably monitor mood and cognition, helping personalize care.¹²
The Role of Technology and AI
Technology now underpins nearly every step of neuroscience innovation, from early discovery to patient monitoring. AI accelerates target identification, molecule design, and trial optimization. Digital endpoints such as sleep, activity, and cognition create sensitive, frequent, real-world measures that can shorten studies and de-risk decisions.
Industry Momentum and Investment
CNS investment is surging. Roche has about 21 CNS project,s and AbbVie has about 16. Biogen maintains roughly 10 neurology assets, and Lundbeck remains deeply focused on CNS. Venture funding and M&A in neurotech and psychedelics have risen sharply. Partnerships span big pharma, AI platforms, and digital therapeutics.
Persistent Challenges
● Attrition and cost: Attrition and cost remain major barriers, with only ~8% of neuropsychiatric drug candidates succeeding compared to ~15% across all therapeutic areas.
● Safety and ethics: Amyloid antibodies require MRI monitoring for ARIA. Eske tamine needs REMS. Psychedelics require controlled settings. Gene therapies face delivery and long-term safety questions. Despite these hurdles, steady investment and strong clinical results continue to attract global interest in neuroscience R&D.
● Access and affordability: Prices are high, for example, donanemab can cost tens of thousands of dollars per year and even higher in the United States, with gradual coverage and specialized-center rollout.
Market Outlook
The CNS therapeutics market was ~$130B in 2024 and could reach ~$255B by 2030 with a CAGR of 7.7%.¹³ Neurodegeneration may grow above 11% CAGR with aging populations. Alzheimer’s drugs may reach ~$15.6B by 2030 as adoption expands. Rapid-acting antidepressants and psychedelics may reach ~$13B by 2030. As these markets expand, innovation across Alzheimer’s, depression, and other CNS disorders is expected to accelerate. With multiple late-stage programs, analysts see the 2020s as a potential golden era for brain medicines.
Conclusion
Neuroscience is making strong progress again. New discoveries in biology, better biomarkers, AI tools, and supportive regulations have led to treatments that can slow Alzheimer’s and rapidly relieve depression. Challenges like high costs and safety issues still exist, but research and innovation are moving fast. If this continues, the next decade could greatly improve how brain disorders are treated.
Frequently Asked Questions (FAQ)
1. Why are companies re-investing in neuroscience?
Better biology, robust biomarkers, AI-enabled design, and early wins such as lecanemab’s clinical benefit have improved the risk–reward profile.
2. Biggest breakthroughs in Alzheimer’s?
Lecanemab and donanemab are the first agents to show slowed clinical decline alongside plaque clearance. Aducanumab set a regulatory precedent.
3. How do these Alzheimer’s drugs work?
They bind amyloid-β, promote plaque removal, and greater clearance correlates with slower tau spread and clinical decline.
4. Are they widely available?
U.S. approvals exist for early Alzheimer’s disease. Access requires infusions, MRI monitoring for ARIA, and payer alignment. Costs are substantial.
5. What makes new antidepressants different?
They act on glutamate and neuroplasticity, for example esket amine, and can deliver relief within hours to days instead of weeks for SSRIs.
References
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2. Wang J, Huang S, Lan G, et al. Diagnostic accuracy of plasma p‐tau217/Aβ42 for Alzheimer’s disease in clinical and community cohorts. Alzheimer’s & Dementia. 2025;21(3). doi:https://doi.org/10.1002/alz.70038
3. Emish M, Young SD. Remote Wearable Neuroimaging Devices for Health Monitoring and Neurophenotyping: A Scoping Review. Biomimetics. 2024;9(4):237-237. doi:https://doi.org/10.3390/biomimetics9040237
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5. Grinstein JD. The Pharma Phoenix: BioXcel Therapeutics Uses AI to Repurpose Shelved Drugs. Inside Precision Medicine. Published June 10, 2024. Accessed October 22, 2025. https://www.insideprecisionmedicine.com/topics/informatics/the-pharma-phoenix-bioxcel-therapeutics-uses-ai-to-repurpose-shelved-drugs/
6. Office. FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. U.S. Food and Drug Administration. Published 2024. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval?
7. Janssen Announces U.S. FDA Approval of SPRAVATOTM (esketa mine) CIII Nasal Spray for Adults with Treatment-Resistant Depression (TRD) Who Have Cycled Through Multiple Treatments Without Relief. JNJ.com. Published March 6, 2019. https://www.jnj.com/media-center/press-releases/janssen-announces-u-s-fda-approval-of-spravatotm-esketa mine-ciii-nasal-spray-for-adults-with-treatment-resistant-depression-trd-who-have-cycled-through-multiple-treatments-without-relie
8. Office. FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. U.S. Food and Drug Administration. Published 2024. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval?
9. Lu M, Kim MJ, Collins EC, et al. Posttreatment Amyloid Levels and Clinical Outcomes Following Donanemab for Early Symptomatic Alzheimer Disease. JAMA Neurology. Published online October 13, 2025. doi:https://doi.org/10.1001/jamaneurol.2025.3869
10. Alario AA, Niciu MJ. (Es)Keta mine for Suicidal Ideation and Behavior: Clinical Efficacy. Chronic Stress. 2022;6:247054702211280. doi:https://doi.org/10.1177/24705470221128017
11. Goodwin GM, Aaronson ST, Alvarez O, et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine. 2022;387(18):1637-1648. doi:https://doi.org/10.1056/nejmoa2206443
12. Shah RV, Grennan G, Zafar-Khan M, et al. Personalized machine learning of depressed mood using wearables. Translational Psychiatry. 2021;11(1). doi:https://doi.org/10.1038/s41398-021-01445-0
13. Central Nervous System Therapeutic Market Size Report, 2028. www.grandviewresearch.com. https://www.grandviewresearch.com/industry-analysis/central-nervous-system-cns-therapeutic-market
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