On July 2nd local time, Lilly (NYSE: LLY) announced that Kisunla (donanemab, 350mg/20mL) has been approved by the US FDA for the treatment of early-stage symptoms of Alzheimer's disease (AD), including mild cognitive impairment (MCI) patients and AD patients with mild dementia.
Just a month ago, donanemab received a 11:0 vote from the FDA Advisory Committee on Peripheral and Central Nervous System Drugs (PCNS) in the United States, unanimously stating that the benefits of donanemab for treating early-stage symptomatic Alzheimer's disease patients outweigh the safety risks. At that time, there were expectations in the industry that the vote would clear the way for the FDA to make a final decision on this therapy.
Alzheimer's disease is a progressive and irreversible neurodegenerative brain disease, with a complex etiology and unclear pathogenesis. The amyloid cascade hypothesis is currently the most recognized mainstream hypothesis in academia. In recent years, the successful clinical trials of multiple novel A β targeted biological agents, including Leqembi (hereinafter referred to as "lencamab") and donanemab, have further confirmed the correctness of this hypothesis and brought breakthrough progress to the field of AD treatment.
"Amyloid protein is a naturally occurring protein in the body that can aggregate to form amyloid plaques. The excessive accumulation of amyloid plaques in the brain may lead to memory and thinking problems associated with Alzheimer's disease." Lilly stated, "The monthly Kisunla is the first evidence to suggest that treatment can be stopped after amyloid plaques are cleared, so it is expected that this therapy can reduce treatment costs and reduce infusion frequency."
"With the increasing aging of the global population, the incidence rate of AD is rising, which has brought a huge burden to the social medical system. However, the treatment of AD is still a world problem at present, and the market demand for effective drugs is undoubtedly huge." Industry insiders have emphasized to 21st Century Business Herald that the key lies in early screening interventions to delay the onset of the disease.
Developing a turning point for "Death Valley"
Alzheimer's disease can lead to intellectual disabilities, mental abnormalities, and loss of social and life functions in patients, seriously affecting their cognitive abilities and normal life. Its new drug development has a recognized highest failure rate of 99.6% in the industry, known as the "death valley" of drug development, and a large number of patients have long been in the dilemma of lacking medical treatment and medication.
The approval for the launch of donanemab is based on the results of the TRAILBLAZER-ALZ 2 trial. In the third phase of the study, individuals with the least disease progression had the most significant effect of using donanemab. Comparing the two groups of experimental participants, the Donanemab group showed a 35% slower decline in the comprehensive Alzheimer's disease assessment scale (iADRS) compared to the placebo group; In addition, donanemab reduced the risk of patients progressing to the next stage of the disease by 39%.
Compared to the beginning of the study, the donanemab group showed an average reduction of 61% in amyloid plaques at 6 months, 80% at 12 months, and 84% at 18 months. When the patient reaches the predetermined standard for clearing amyloid plaques, the subject stops using dononemab. The results showed that 17% of patients completed treatment at 6 months, 47% completed treatment at 12 months, and 69% completed treatment at 18 months.
According to a press release from Lilly, the price of donanemab is $695.65 per bottle (approximately 5059.67 yuan per bottle), and the total cost will vary depending on the time the patient completes treatment. According to the above experimental results, the cost of treatment for 6 months is $12522 (approximately 91076.26 yuan), $32000 (approximately 232745.60 yuan) for 12 months, and $48696 (approximately 354180.62 yuan) for 18 months.
In addition to providing new treatment options for Alzheimer's disease patients, safety cannot be ignored. Clinical data shows that 36.8% of individuals in the dononemab treatment group experience amyloid associated imaging abnormalities (ARIA), which typically manifest as temporary swelling or micro bleeding in one or more regions of the brain, and in some cases, these may be severe or even fatal.
"Donanemab can also cause certain types of allergic reactions, some of which may be severe and life-threatening, typically occurring during or within 30 minutes after infusion. Headache is another common side effect," said a Lilly press release.
Donanemab has become the second drug of its kind to be marketed for the treatment of Alzheimer's disease, following similar antibodies such as lencamab from Eisai/Bojian. Meanwhile, 21st Century Business Herald reporters also found that the official website of the Drug Evaluation Center of the National Medical Products Administration announced in November 2023 that donanemab injection has been included in the list of priority evaluation varieties.
Equal emphasis on early screening and new drug launch
Alzheimer's disease induced dementia is the most common form of dementia, accounting for 60% to 80% of all cases. Currently, there are over 55 million dementia patients worldwide, and it is expected that this number will increase to nearly 139 million by 2050. More than 10 million new cases of dementia are diagnosed worldwide every year, which means there is one new case every 3.2 seconds, significantly increasing the burden of care on society and families.
Domestically, epidemiological surveys have shown that there are approximately 15.07 million dementia patients among the population aged 60 and above in China, including approximately 9.83 million with Alzheimer's disease and 38.77 million with mild cognitive impairment (MCI). Alzheimer's disease has become the fifth leading cause of death in China, with an annual disease expenditure of up to $167.7 billion, placing a heavy economic and social burden on the public health system.
Millions of patients are waiting for the development and launch of innovative drugs. On July 6, 2023, the FDA approved the application for a supplementary biological agent license (sBLA) for lencamab 100mg/mL injection. Lencamab has become the first AD therapy targeting beta amyloid protein. On January 9th of this year, lencamizumab (trade name: Xiebao®) was officially approved by the National Medical Products Administration (NMPA) to enter China.
On June 26th, the first Chinese prescription of lencamizumab was prescribed in the Neurology High Invasive Center ward of the National Center for Neurology and Xuanwu Hospital of Capital Medical University. On the same day, lencamab was also prescribed for the first time at Huashan Hospital affiliated with Fudan University. It is reported that the first batch of 6 patients diagnosed with early AD at Huashan Hospital will receive treatment for a period of 18 months, with two monthly infusions of lencamab.
According to Dr. Yu Jintai, the head of the cognitive impairment subspecialty in the Department of Neurology at Huashan Hospital, evaluating whether a patient is suitable for using lencamab requires the following four steps: the patient has symptoms of cognitive decline and is identified as an early patient through neuropsychological assessment; Medical history, physical examination, blood and head magnetic resonance imaging (MRI) tests suggest that cognitive impairment may be caused by AD, and other contraindications are excluded; Diagnose AD through brain positron emission computed tomography (PET-CT) or cerebrospinal fluid testing; APOE genotype testing evaluates the risk of side effects.
According to the official website of Weicai, in China, lencamab will be the first to be sold in the self funded market. Weicai will collaborate with a medical insurance company to develop and launch a medical insurance plan specifically for Alzheimer's disease, covering some medical expenses.
According to publicly available information, the domestic pricing for lencamab injection is 2508 yuan per bottle, with a specification of 200 milligrams (2 milliliters) per bottle. The recommended dose for Happy Protection is 10 milligrams per kilogram of body weight, to be used every two weeks. The specific cost may vary depending on the patient's weight. Based on this calculation, the monthly treatment cost for a patient weighing 60 kilograms is about 15000 yuan, and the annual treatment cost is about 180000 yuan.
Faced with a large patient population and medication demand, domestic pharmaceutical companies are also accelerating research and development. Hengrui Pharmaceuticals disclosed in its 2023 annual report that clinical trials of anti A β monoclonal antibody SHR-1707 for the treatment of Alzheimer's disease in non tumor innovative products are proceeding smoothly in Australia; Tonghua Jinma also disclosed in its 2023 annual report that its amber octahydrazine tablets have completed unblinding, statistical analysis reports, and clinical trial summary reports. The next step will be to submit a new drug marketing application.
Li Xia, Director of the Geriatric Psychiatry Department at the Shanghai Mental Health Center, once emphasized to 21st Century Business Herald reporters, "The progression of Alzheimer's disease goes through mild, moderate, and severe stages, and drug use cannot reverse the progression of the disease. For Alzheimer's patients, early screening and diagnosis are crucial, and early intervention can delay the onset of the disease. This also means that the probability of patients developing into severe illness and completely losing autonomy in their lifetime will decrease."
Therefore, upstream diagnosis is still indispensable beyond drug development. According to a research report by Guojin Securities, in areas with severe symptoms, diagnosis should be prioritized, and progress in disease understanding and breakthroughs in new drugs will promote the accelerated growth of related diagnostic tracks. At present, there are relatively few manufacturers participating in the AD diagnosis track in China, mainly focusing on emerging technology research directions. Diagnosis is expected to usher in sales opportunities with the increase of drug volume.