AstraZeneca Exits CNS: Two Strategic Signals and Pipeline Implications

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Author | Wu Yue

/ 01 /

AstraZeneca's Exit

In the first quarter, AstraZeneca terminated multiple neuroscience projects, including the Alzheimer's drug MEDI1814, which had been in collaboration with Eli Lilly for many years, MEDI0618 for migraine treatment, and MEDI7352 targeting osteoarthritis pain and diabetic neuropathy.

Among them, MEDI1814 is an anti-amyloid β42 (Aβ42) monoclonal antibody that was once highly anticipated as potentially "changing the landscape of Alzheimer's disease treatment." At the end of 2016, Lilly and AstraZeneca reached a cooperation agreement to jointly develop MEDI1814, for which Lilly paid $30 million upfront.

At that time, the highly anticipated anti-amyloid-beta therapy solanezumab from Eli Lilly had just failed in its third large-scale Phase III EXPEDITION3 trial. However, according to AstraZeneca, MEDI1814 has a mechanism of action entirely different from other investigational Alzheimer's antibody drugs. MEDI1814 binds to and clears circulating Aβ peptides, thereby limiting their aggregation into toxic oligomers. This helps reduce the accumulation of amyloid-beta plaques in the brains of Alzheimer's patients, potentially slowing disease progression.

In previously disclosed preclinical studies and early clinical trials, MEDI1814 also demonstrated the potential to reduce Aβ42 peptide levels in a dose-dependent manner, which may help slow the progression of Alzheimer's disease.

Nevertheless, AstraZeneca still decided to "cut off the arm to save the body." The dissolution of teams and layoffs soon followed. During the Q1 earnings call, AstraZeneca announced its complete withdrawal from the neuroscience field.

Sharon Barr, Executive Vice President of AstraZeneca Biopharmaceuticals R&D, stated, "We have closed the neuroscience program and are seeking partners for some projects, which means the dissolution of AstraZeneca's neuroscience team."

This will lead to "a very small number of positions facing the risk of layoffs," but AstraZeneca emphasized that this is a necessary measure for strategic focus. During a teleconference, CEO Pascal Soriot frankly stated, "We cannot support all areas at the same time; CNS is more suitable to be managed by companies specializing in this field."

/ 02 /

The Ice and Fire of CNS

Before AstraZeneca, giants like Pfizer and Amgen had long "exited" the CNS field, while Biogen, which has focused on this area, has also been expanding into other tracks in recent years.

This is because the CNS field is experiencing a "Game of Thrones" moment.

On the one hand, the continuously rising number of patients is expanding the global CNS market, catalyzing the birth of an increasing number of new drugs, with major pharmaceutical companies such as Johnson & Johnson and Eli Lilly also ramping up their investment in the CNS sector.

In 2024, we witnessed a historic moment in the field of schizophrenia as KarXT, developed by Karuna, was approved by the FDA for market release. This marks the arrival of the first new schizophrenia drug in 35 years and validates BMS's decision to acquire Karuna for $14 billion.

Breakthroughs have also been made in Alzheimer's disease, with the FDA approving donanemab for the treatment of adult patients with early Alzheimer's disease. Despite safety concerns that cannot be ignored, the FDA's independent scientific advisory committee unanimously voted in favor, stating that the current evidence sufficiently demonstrates the drug's efficacy and that its benefits outweigh the risks. The core reason behind this is that Alzheimer's patients have endured a long period without new drug options.

On the other hand, compared with breakthroughs and success, failure is more common.

A typical example is AbbVie, which experienced three clinical failures last November. Among them, its major bet in the schizophrenia field, emraclidine, failed to meet the expected endpoints in two Phase II studies for schizophrenia. Upon the release of this news, AbbVie's stock price plummeted by 12.57%, wiping out more than 40 billion U.S. dollars of its market value overnight.

In January this year, Boehringer Ingelheim also stumbled in the field of schizophrenia treatment. Failures in the Alzheimer's disease area have been even more frequent, with CNS drug pioneers like Sage, Cassava Sciences, Alector/AbbVie, and others facing setbacks.

In the face of painful lessons, AbbVie is also reevaluating its investment strategy in the field of central nervous system diseases. At the 2025 JPM conference, AbbVie revealed: "When investing heavily in early-stage data research in the future, we will definitely reconsider and weigh our options carefully."

Obviously, for some large pharmaceutical companies, the long-term investment and high risks in neuroscience have reduced its appeal. This is not difficult to understand. Although the prospects of the CNS field are attractive, the difficulty of success can be described as hell mode: data shows that the success rate of central nervous system drug development is only 6%, less than half the success rate of other drug developments.

The core reason lies in the fact that every step—ranging from unclear mechanisms, to the difficulty in validating animal models, and the immense challenges in clinical development—poses a major obstacle for CNS drug development.

At the same time, under fierce market competition, commercial returns are also an issue that pharmaceutical companies have to consider. With many pharmaceutical companies clustered together, if the developed products are difficult to stand out, returns will naturally be out of the question. This is a great test for pharmaceutical companies in terms of funding and confidence.

For instance, AstraZeneca terminated MEDI0618, a new migraine drug, which is a PAR2 (protease-activated receptor 2) antagonist monoclonal antibody. In recent years, the competition in the migraine treatment field has become increasingly fierce, with new drugs constantly emerging, including CGRP (calcitonin gene-related peptide) receptor antagonists, etc. These drugs have not only achieved significant clinical effects in the prevention and treatment of migraines, but pharmaceutical companies have also escalated competition to aspects like dosage forms and dosing cycles.

When pharmaceutical companies must make a choice, the clear returns in areas such as oncology seem more attractive. For AstraZeneca, in the first quarter of this year, its oncology business revenue reached $5.6 billion, accounting for 41% of total revenue. The sales of the diabetes drug dapagliflozin reached $2 billion, a year-on-year increase of 15%. In comparison, the neuroscience pipeline is almost negligible.

/ 03 /

"Focus" Survival Rules

Every time financial reports are disclosed, in addition to seeing a company's operating conditions and performance over a certain period, one can also glimpse the company's strategic adjustments.

If biotech companies are forced to downsize and cut pipelines due to survival pressures, then the fact that larger, more established pharmaceutical companies have collectively started to "scale down" is even more telling.

For AstraZeneca, the patent cliff is imminent, and changes must be made. After exiting neuroscience, AstraZeneca plans to focus its resources on four core areas:

• In oncology, AstraZeneca continues to expand indications with key products such as Tagrisso and Imfinzi, while advancing the development of ADC drugs (e.g., Enhertu) and bispecific antibodies.

  
  

• Respiratory and Immunology, focusing on diseases such as asthma, chronic obstructive pulmonary disease, and atopic dermatitis, accelerating the localized production of products like Budesonide/Formoterol inhalation aerosol.

  
  

• Cardiovascular, Renal and Metabolic Diseases: Farxiga's Indication Expansion to Chronic Kidney Disease and Heart Failure; Clinical Progress of Oral GLP-1 Drugs to Become the Focus of the Next Stage.

  
  

• Rare diseases, strengthening the layout of gene therapy and enzyme replacement therapy through acquisitions and collaborations, such as the development of drugs for spinal muscular atrophy.

AstraZeneca emphasized that this strategic adjustment will "ensure resources are allocated to projects that can deliver long-term value." For instance, the clinical data of oral GLP-1 drugs and the progress of the breast cancer candidate drug camizestrant will directly influence future capacity investment decisions.

In fact, in the past two years, multinational pharmaceutical giants have been accelerating their streamlining efforts to become more focused. The purpose is to reinforce core areas, expand existing advantages, and delay the decline in revenue growth.

Novartis may be the fastest "slimming down" among major pharmaceutical companies. Starting from the spin-off of Sandoz in 2022, within a year, the number of solid tumor drugs in Novartis' pipeline was reduced from 42 to 28, with most of the abandoned projects being in Phase I.

Shreeram Aradhye, President of Global Pharmaceutical Development and Chief Medical Officer, once stated externally that the company's reduction of its pipeline is mainly based on two considerations: on one hand, identifying core therapeutic areas; on the other hand, focusing resources and manpower on the most critical treatment areas to further enhance the success rate of R&D.

In the first quarter of this year, major pharmaceutical companies continued to optimize their pipelines. For instance, BMS stated in its latest earnings report that it plans to cut $1.5 billion in costs by large-scale restructuring before the end of 2025, and will lay off approximately 2,200 employees globally, accounting for 6% of its total workforce.

Currently, BMS has approximately 12 projects that have been halted or outsourced for development, including the follow-up version of drug Y, SIRPα, and BET-targeted drugs. The company will continue to review its product pipeline for the remainder of the year.

"Focus" has become the common choice.

After all, a pharmaceutical company's energy is always limited, and resources such as manpower, financial capacity, and materials are also limited. To maximize the effect of these limited resources, they must be concentrated in use—focused on areas of strength to continuously seek substantial breakthroughs, enhance competitive advantages, and further widen one’s moat.

Especially considering the current uncertain environment and the patent cliff, even large pharmaceutical companies with more resource advantages have begun to take precautions and proactively downsize, accelerating their withdrawal from less advantageous fields to become more focused.

Times have changed, and people are now more concerned about security and certainty. For pharmaceutical companies in China, further focus and how to build a pipeline that meets the actual needs of the market have become urgent issues for each company to consider.

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