The loss of control can strike out of the blue, even when preceded by minor symptoms.
When Zhang Li’s mother began experiencing symptoms like dizziness and poor memory, it was initially dismissed as a mild stroke—a minor ailment. However, one day, when she failed to redeem a coupon on a shopping app, she suddenly grew agitated and started feeling completely incompetent. She then forgot her own and her family’s names and the layout of their home. It was only when she lost all sense of direction and security that Zhang was informed by doctors that this was Alzheimer’s disease (AD), commonly referred to as dementia.
Clinically, this moment marks the starting point for many AD patients and their families seeking medical advice. However, from the perspective of disease progression, most patients have already reached the “point of no return” at the moderate to severe stages, when it becomes difficult for drug treatments to achieve any significant effect.
Recently, two drugs targeting early-stage AD patients have shown progress. In early July, Eli Lilly’s new amyloid-beta (Aβ) targeting drug, donanemab, was approved for the US market, becoming the second fully approved AD treatment by the US Food and Drug Administration (FDA). This drug has also been included in the priority review list by China’s National Medical Products Administration (NMPA). Another similar AD drug by Biogen and Eisai was approved earlier and has recently been used in clinical settings in China.
The medical community is excited that AD treatments are finally transitioning from symptomatic interventions to the era of precision-targeted therapies. For family members of patients, like Zhang, who have watched their loved ones deteriorate despite treatment, this progress might offer some comfort.
Despite the high cost of these new drugs, with annual treatment fees around RMB 200,000, and the current lack of insurance coverage, discussions about these new drugs have been constant in Zhang’s patient support group: who has used them, where are they available, and how effective are they? Those under immense caregiving pressure are searching for hope for their families and themselves.
As the treatment window opens, how will these new drugs disrupt the AD treatment market?
A ray of hope for early-stage AD patients
Before donanemab, lecanemab, sold under the brand Leqembi, began usage in China at the end of June. In Phase 3 clinical trials, patients using lecanemab experienced a 27% slower decline in cognitive function and daily living abilities compared to the control group.
Several medical institutions that have listed or are about to introduce lecanemab have reported strong patient interest in trying the new drug. Xue Zhanyou, a neurologist at Shanghai Donglei Brain Hospital, mentioned that sometimes he receives numerous inquiries about the drug in a single afternoon.
Donanemab, which has recently been approved, has shown even better clinical data, slowing the decline in cognitive levels by 35% and reducing the risk of disease progression to the next stage by 39%.
Interestingly, during the final review meeting before its approval, FDA advisors unanimously voted 11-0 in favor of donanemab. According to various media reports, these experts did not focus much on the drug’s efficacy as they unanimously found the data convincing, and most discussions revolved around who would benefit from the drug and how it should be applied.
The focus on early-stage patients by regulatory authorities is noteworthy because this area has metaphorically been uncharted territory in the realm of AD treatments.
The AD treatment landscape
From a theoretical standpoint, both drugs follow the amyloid cascade hypothesis—the most widely accepted cause of AD in the academic community. This hypothesis posits that plaques formed by the deposition of Aβ proteins trigger reactions like excessive phosphorylation of tau proteins, leading to neuronal damage and dementia.
Thus, preventing Aβ deposition is seen as a viable etiological treatment, with the significant advantage of being able to intervene in AD development from an earlier stage.
Based on Aβ biomarker test results and clinical symptoms, AD can be classified into three stages: preclinical, mild cognitive impairment, and dementia (mild, moderate, severe), with durations typically lasting 1–3 years, 2–10 years, and 8–12 years, respectively.
Currently, most AD patients are diagnosed in the middle to late stages. “At this point, cognitive damage is irreversible, and the significance of saving the patient is minimal,” Zhang said. As a pharmaceutical researcher, Zhang has seen firsthand the importance of targeted drugs in the treatment of AD.
Traditional AD drugs, such as memantine and GV-971 (sodium oligomannate), primarily target moderate to severe patients and generally have insufficient efficacy, providing short-term symptomatic relief but fail to address the underlying causes and slow disease progression. “Patients’ responses to the drugs vary—some show slight improvement in memory, while others do not worsen,” Xue explained.
“The goal of AD treatment should be to delay the progression from early to moderate and severe stages within a normal lifespan,” Zhang said. “For instance, if the disease usually progresses from early to moderate in five years, these drugs can extend this period further.” Lecanemab and donanemab aim to achieve this by clearing Aβ.
Despite the inability to stop disease progression, the trend toward delaying it is viewed positively within the industry. However, from the patients’ perspective, uncertainties remain. So far, only three drugs based on the amyloid cascade hypothesis have been approved, with comprehensive approval granted only to lecanemab and donanemab. Due to their recent introduction, follow-up data is still limited. In terms of safety, Aβ antibodies are generally associated with risks of amyloid-related imaging abnormalities, including brain edema and hemorrhage.
Financial burden and treatment choices
Despite the potentially better outcomes, the high cost remains a significant barrier for many patients. Eli Lilly’s donanemab costs USD 695.65 per 350-milligram injection. With a dosing schedule of 750 mg for the first three doses followed by 1400 mg every four weeks, the annual cost is approximately USD 32,000, or around RMB 230,000.
Lecanemab’s annual treatment cost in the US is USD 26,500 and RMB 180,000 in China.
Some in the pharmaceutical industry view these prices as fair. However, how these prices will influence actual purchase decisions remains uncertain. For one, traditional AD drugs are much cheaper. In China, early-stage drug costs are generally over RMB 1,000 per month, with annual costs around RMB 10,000. In 2019, Green Valley’s GV-971 was priced at RMB 3,580 per month, sparking significant controversy due to its high cost.
Overseas, sales data also highlight the economic challenges. Lecanemab had first-year sales of only USD 10 million despite its early 2023 launch. Although sales accelerated in 2024, reaching USD 19 million in the first quarter, it still falls short of Eisai’s target of USD 7 billion by 2030. With donanemab entering the market, direct competition between the two products may influence their market performance.
The first Aβ drug, aducanumab, sold under the brand name Aduhelm, with an annual treatment cost of USD 56,000, faced efficacy controversies and was not covered by the US Medicare program. Its sales in 2021 and 2022 combined did not exceed USD 10 million. In early 2023, Biogen restructured its AD portfolio, abandoning Aduhelm and returning its rights to Swiss partner Neurimmune.
The economic paradox is evident: with no cure in sight, is it worth spending RMB 200,000 annually for a predetermined outcome?
Seeking better treatments
In late June, after Biogen’s special drug was launched, hospitals in Shanghai and Zhejiang began administering it to early-stage AD patients. The topic quickly trended on social media, with many netizens calling it a life-saving drug and hoping it could preserve the memories of the elderly.
While some believe an expenditure approximating RMB 180,000 a year is worth it, concerns that the state of disability won’t be avoided, just delayed, amplify hesitations. Zhang noted that, in some family groups, the most hoped-for result among patients and their families is ultimately still a cure.
Even if the goal is merely to delay progression, the annual medication cost of RMB 180,000, combined with the burden of AD care, is immense. “As a neurodegenerative disease, AD patients will experience functional decline in various systems, such as being unable to swallow, forgetting temperature sensations, and muscles forgetting how to perform voluntary actions, requiring at least 1–2 full-time caregivers,” Zhang said.
Data disclosed at a 2023 health conference in China indicated that, with an estimated 10 million patients, the annual economic burden of AD in China is RMB 1.6 trillion. Facing such a heavy economic burden, pharmaceutical companies are also seeking solutions.
According to Eli Lilly, unlike the previous two Aβ drugs that require continuous use, donanemab significantly reduces amyloid plaque levels, with an average reduction of 84% after 18 months of treatment. After stopping the medication, the reaccumulation of amyloid protein is slow.
Assuming the statistic’s validity, this would make it the first Aβ product with evidence supporting the cessation of treatment after amyloid plaque clearance. The most direct outcome is fewer doses, lower costs, and reduced treatment expenses.
However, FDA reviewers have mentioned that, while this clinical trial design is innovative, the data is limited, leaving uncertainties about how much amyloid protein needs to be reduced before stopping the medication, and what methods doctors should use to determine when to stop.
Other pharmaceutical industry insiders have suggested that it is still unclear whether amyloid protein is the direct cause of AD or just one of the mechanisms involved. Therefore, if the current capability is only to slow cognitive decline, the development of other drug or non-drug treatment methods remains essential.
Awaiting a miracle drug
In the pharmaceutical field, AD was once considered an R&D “black hole.” According to the Pharmaceutical Research and Manufacturers of America (PhRMA), from 2000–2017, global R&D investment in AD drugs exceeded USD 600 billion, with over 300 clinical failures, a failure rate of 99.6%.
Today, while new drug development pathways are being explored, existing products are still imperfect, and the demand for a cure remains strong. Consequently, the motivation for new entrants to tap into the AD treatment market is growing stronger. Public data suggests that the global AD drug market could exceed USD 30 billion by 2025.
Industry insiders noted that, following Aduhelm’s launch in 2021, related research has been evolving rapidly, with regular updates in research findings. According to data from the US National Library of Medicine, as of early 2023, over 160 registered clinical trials targeting AD prevention, mild cognitive impairment, and dementia stages were covering 127 drugs. In 2023 alone, 35 new AD clinical trials were added.
Since Aduhelm, AD has gradually emerged from a period of technical silence. Apart from the progression of Aβ drug development, new targets and pathological mechanisms, such as tau protein, neuroinflammation, and multi-target treatments, are continually producing new results. For instance, Eli Lilly is exploring remternetug, an experimental version of donanemab that targets an Aβ subtype called “N3pG” and may allow for subcutaneous administration. This drug is currently in Phase 3 clinical trials.
In China, many companies are involved in AD research. According to Pharmcube data, by the end of 2023, nearly 40 Chinese pharmaceutical companies and research institutions had two or more AD pipelines, including Hengrui Pharmaceuticals, Simcere Pharmaceutical Group, and Tonghua Golden-Horse Pharmaceutical Industry. Exploring popular targets like GLP-1, which is considered a potential treatment target for AD, Chinese companies such as CSPC Pharmaceutical Group, Tianjin Biopharmaceutical, and QL Biopharm have obtained clinical trial permits for their respective drug solutions.
Additionally, drug research is bringing new opportunities to upstream and downstream industries such as contract research organizations (CROs), diagnostic tools, and insurance payment systems.
One prominent example is diagnostics. AD diagnosis rates are very low—until 2019, over 70% of AD patients in China had never sought treatment for dementia. In this aspect, deep research into biomarkers is playing a key role. Compared to traditional positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarker tests, plasma biomarkers offer advantages such as being less invasive and cost-effective. Some products have been approved for use in Europe and the US or have obtained breakthrough device designations. However, such products are not yet approved in China.
While exploration of AD treatments remains an ongoing process, the hope is that such endeavors will unveil incrementally better options for patients, sooner rather than later.
KrASIA Connection features translated and adapted content that was originally published by 36Kr. This article was written by Hu Xiangyun for 36Kr.