The last trillion-dollar untapped market for global innovative drugs

In the past two years, the investment and financing enthusiasm in the field of neuroscience has been continuously rising. Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, these indications that were once regarded as R & D black holes are re - entering the priority lists of major pharmaceutical companies.

The underlying logic is not complicated: the leading effect in the metabolic track has formed barriers, and the homogeneous competition in the oncology track has intensified. Nervous system diseases (CNS) are one of the few fields with a large number of unmet needs and a high enough technical threshold.

The global CNS drug market was about $140 billion in 2025 and is expected to exceed $280 billion by 2034. The Alzheimer's disease drug market is growing at the fastest rate, and it is expected to expand from less than $10 billion in 2025 to more than $30 billion by 2030. After oncology and metabolism, this is the last trillion - level untapped market in the pharmaceutical industry.

The problem is that although the mechanisms are being decoded one by one, the transformation from mechanism to drug is still the steepest slope in this industry.

01

The Steepest Slope

Alzheimer's disease is the most comprehensive profile for understanding the difficulty of conquering CNS.

In the past forty years, the R & D failure rate in this field has been as high as 99.6%, and hundreds of candidate drugs have failed in Phase III. Leqembi, jointly developed by Biogen and Eisai, was approved in 2023, which for the first time verified the hypothesis that removing amyloid plaques can slow down cognitive decline.

However, the problem is that after the verification, the resistance to clinical application far exceeds expectations. Patients need to receive intravenous infusions every two weeks and undergo regular MRI to monitor ARIA. About 12% to 15% of patients experience imaging cerebral edema or micro - bleeding. Although most of them are asymptomatic, the monitoring itself has excluded most community hospitals. Meanwhile, the prescription volume is far lower than the initial estimate of $10 billion by analysts.

In essence, this is a dilemma in clinical transformation: the drug is effective, but the frictional costs in the three links of delivery method, safety monitoring, and patient screening are too high.

In the first quarter of 2026, several key progresses began to break through these friction points one by one, targeting three fronts: delivery, screening, and endpoint design.

1. The blood - brain barrier is the first front.

The root of nervous system drugs lies in the blood - brain barrier. This wall composed of endothelial cells blocks 98% of small molecules and almost all macromolecules. Two technical routes are being tried in parallel to cross this barrier:

One is gene replacement. Using AAV vectors to directly deliver the correct gene to the nucleus, a single administration can achieve lifelong expression. Spark, a subsidiary of Roche, reached a cooperation with SpliceBio in April to develop the next - generation AAV vectors for inherited retinal diseases. The intravitreal injection AAV system obtained by Novartis through the acquisition of Vedere Bio has changed the administration method from sub - retinal injection to intravitreal injection, greatly reducing the surgical threshold.

The other is gene silencing. Using siRNA or antisense oligonucleotides to bind to the target mRNA, degrading or blocking translation, silencing the disease - causing gene at the RNA level without changing the DNA, and requiring regular administration. Cemdisiran, a collaboration between Regeneron and Alnylam, was successful in the Phase III trial of myasthenia gravis. With subcutaneous injection once every 12 weeks, the administration scenario has shifted from the hospital infusion center to the family clinic. This is the first time that small nucleic acids have completed the whole process in a neurological autoimmune disease.

2. Patient screening is the second front.

A large part of the reason for the failure of neuroscience clinical trials is enrolling the wrong patients. When the disease has reached the advanced stage and a large number of neurons have died, no mechanism can save the situation.

Eli Lilly only enrolls early - stage patients with tau protein deposition reaching a specific threshold in its Phase III Alzheimer's disease trial, screening out those who are biologically unsuitable for treatment.

Biogen's tau - targeted ASO drug diranersen failed to meet the primary endpoint in the Phase II trial at the AAN annual meeting in April. However, subgroup analysis showed that patients with a high baseline tau level had a stronger signal. This is the entire reason for it to bet on Phase III: it's not that the drug is ineffective, but that the right patients were not found.

3. The innovation of clinical endpoints is the third front.

The FDA issued an industry guideline in 2024, for the first time clearly stating that biomarkers can be used as the basis for accelerated approval of neurodegenerative diseases. In the ALS field, Clene's CNM - Au8 obtained confirmation of the accelerated approval path from the FDA based on neurofilament light chain data, which is the first time.

The regulatory authorities are sending the same signal: for diseases with a long course and where it takes many years to read out differences in clinical endpoints, validated surrogate endpoints can be accepted. The time window from concept verification to market launch is being compressed.

The three fronts point in the same direction: Innovation in neuroscience no longer depends on the discovery of new targets, but on integrating biological mechanisms, biomarker screening, delivery technologies, and clinical endpoint design, and pushing forward through systematic optimization.

02

A Track That Can Provide Single - Product Returns of Billions of Dollars

The experience of BTK inhibitors in multiple sclerosis is a repetition of the same logic.

Sanofi's tolebrutinib reached the endpoint of delaying disability progression in the previous Phase III HERCULES study, but the FDA still issued a complete response letter. Industry speculation points to safety data or CMC. Merck's evobrutinib was completely terminated in the Phase III trial for the same indication due to hepatotoxicity. Novartis's remibrutinib is still in Phase II, with solid but unremarkable data.

For the same target and the same track, three pipelines are stuck at different stages. The mechanism is correct, and the one who closes the safety loop first will be able to move forward.

The bets of major pharmaceutical companies are becoming more systematic. Biogen doesn't give up after failure, Sanofi continues to find a way after receiving a CRL, and Novartis increases its investment in Phase II. In the past, they bet on a single target, but now they bet on the maturity of a technological system. The one who closes the three loops of delivery, screening, and endpoint design first will occupy the revenue gap in the next decade.

To see how large the gap is, just look at the global pharmaceutical ranking in Q1 2026: Merck fell out of the top five due to the expiration of the Keytruda patent in 2028, Novartis's revenue declined by 5% due to the expiration of the Entresto patent, and Pfizer dropped to the 8th place due to the decline of the COVID - 19 vaccine. Behind each company's setback is a patent cliff that is too late to fill.

Behind each company's setback is a patent cliff that is too late to fill, and neuroscience is one of the few tracks that can provide single - product returns of billions of dollars.

03

China's Ticket

For Chinese innovative pharmaceutical companies, nervous system diseases used to be the least attractive track. The R & D cycle is long, the failure rate is high, and the clinical market is almost monopolized by major pharmaceutical companies. However, changes have occurred.

In May 2026, Fosun Pharma locked in the global rights of the Alzheimer's disease new drug AR1001 of South Korea's AriBio company for $60 million. AR1001 is an oral small molecule targeting amyloid protein, and the Phase III data will be released this year. Leqembi has opened up market awareness and prescription habits with its injection dosage form. Oral drugs can shift the treatment scenario from the infusion center every two weeks to daily home use, and accessibility itself is a competitive advantage.

What is more worthy of attention is the layout of small nucleic acids in the field of neuroscience. The application for the listing of GSK's hepatitis B ASO drug bepirovirsen in China was rejected in May, which exposed that the CMC review standards for ASO drugs by the NMPA are still being established. However, from a global perspective, this just means that the regulatory framework is being constructed.

Once this path is opened, Chinese companies with siRNA and ASO pipelines will have a clear export path. Because neuroscience is one of the most suitable battlefields for small nucleic acids. The blood - brain barrier's restriction on traditional small molecules and antibody drugs can be directly bypassed by antisense oligonucleotides through intrathecal injection.

The window for this track will not stay open for long. Major pharmaceutical companies are setting priorities with real money, and they are betting on the revenue gap in the next decade. The frictions in each link of delivery, screening, and endpoint design are being overcome one by one. Once the platform is operational, latecomers will have a roadmap.

However, the roadmap will not wait for more people; it will only be taken by those who arrive first.

This article is written based on publicly available information and is only for information exchange, and does not constitute any investment advice.

This article is from the WeChat official account "Medical Shine", author: Zhang Qinghuan, published by 36Kr with authorization.