12 Alzheimer's Disease Investigational Therapies in Clinical Trials in China: Innovations from Eli Lilly, Johnson & Johnson, Hengrui Medicine, and More
Johnson & Johnson
Medical Device R&D and Manufacturer
With the acceleration of global population aging, Alzheimer's Disease (AD), a neurodegenerative disorder, is becoming a major challenge in the field of global public health at an unprecedented rate.According to the latest report from The Lancet[1]It is estimated that by 2050, the global number of people with dementia will triple, increasing from 57 million in 2019 to 153 million. Alzheimer's disease is the leading cause of dementia.Facing such a large patient population and an increasingly heavy disease burden, developing effective drugs for treating AD has become an important goal in the global biopharmaceutical industry.
The good news is that in recent yearsFor ADNew drug development achievedSignificant advancements, such as monoclonal antibody therapies targeting Aβ and oral acetylcholinesterase inhibitor treatments, have been successively approved for marketing.International authoritative journalNatureA feature article published in 2023 pointed out that in recent years, innovative treatment methods in the AD field have been emerging continuously, and some therapies under research have shown future prospects, includingTherapies targeting Tau used in combination with anti-amyloid therapies; blocking the production of pathogenic Tau proteins or reducing amyloid-beta through antibodies, small molecule drugs, or gene therapy; and vaccines against Tau and amyloid., etc. In addition,，With a deeper understanding of the pathogenesis of diseases, more R&D pipelines with new mechanisms and new targets continue to emerge and enter clinical trials.
In China, in addition to the approved drugs, more targetedADThe R&D pipeline of the new drug under development is also continuously advancing.This article reviews 12 investigational new drugs for Alzheimer's disease currently undergoing clinical research in China, based on publicly available information.(Note: This articleFor incomplete statistics,Only inventory some of the new drugs under research for AD clinical trials conducted in China.)
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Lilly: Donanemab Injection
Mechanism of Action: β-Amyloid (Aβ）Antibody
ChinaR&D Stage:Apply for Listing
Donanemab Injection is a product of Eli Lilly and Company（Eli Lilly and Company）A monoclonal antibody developed to bind with the β-amyloid subtype N3pG has been approved by the U.S. FDA in July this year.ApprovalTreatmentAdults with Early Symptoms of Alzheimer's Disease. In China, donanemabWas publicly announced by the CDE as a breakthrough therapy in 2023,For the treatment of early symptomatic Alzheimer's disease, including mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease.
Mechanism of Action:Acetylcholinesterase Inhibitors
ChinaDevelopment Stage: Application for Market Launch
Amber Octahydroaminoacridine Tablets is a small-molecule acetylcholinesterase inhibitor developed by Tonghua Jinma.Can simultaneously inhibit acetylcholinesterase and butyrylcholinesterase,Mainly developed for the treatment of mild to moderate Alzheimer's disease. On August 29 this year,Tonghua JinmaThe Marketing Application for the New Drug, Amber Octahydroaminoacridine Tablets (Category 1)Accepted for Filing。In September 2023, Tonghua Jinma announced the completion of the Phase 3 study of Ambenonium Bromide Tablets for the treatment of mild to moderate Alzheimer's disease.The results showed that the product had a clinically significant effect on the improvement of the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-cog).The incidence of adverse events in terms of safety was lower than that in the control group., and the results are statistically significant.
Runjia Pharmaceuticals: RP902 Tablets
Mechanism of Action: Novel Small-Molecule Drug Targeting Aβ
Clinical Development Stage in China: Phase 2
RP902 tablets are independently developed by Runjia Pharmaceuticals.Stable Isotope-Substituted Small Molecule Class 1 Innovative Drug, with Beta-Amyloid (Aβ) as the Primary Target, intended for the treatment of Alzheimer's disease. According to the introduction in Runjia Pharmaceutical's public materials,This product can significantly inhibit the formation of soluble amyloid protein oligomers directly associated with cognitive decline in AD patients, eliminate or reduce the toxicity of amyloid proteins to nerve cells, and also provide some relief and protection against blood-brain barrier damage.Preclinical pharmacodynamic studies have shown that RP902 significantly improves object recognition memory, spatial memory, and long-term memory impairment in AD model mice; significantly ameliorates hippocampal and cortical neuronal and dendritic damage, and enhances synaptic plasticity; reduces Aβ deposition and the levels of both soluble and insoluble Aβ1-40 and Aβ1-42 in the brains of model mice, with good safety. According to Runjia Pharma's official website, this product is currently in Phase 2 clinical trials.
Zhuo Kai Biology: 50561 Tablets
Mechanism of Action: TargetingActive Forgetting Biological Mechanism
Clinical Development Stage in China: Phase 2a
According to previous press releases from Zhuo Kai Bio, 50561 tablets are one of the products currently under development.Drugs that Inhibit Active Forgetting and Rescue Cognitive Deficits in Alzheimer's DiseasePreviously, in order to address the complex disease mechanisms of AD, the distant connection between traditional targets and disease symptoms, and the poor efficacy of drugs, Professor Yi Zhong's research group from the School of Life Sciences at Tsinghua University established a Drosophila phenotype screening platform to explore treatment paradigms for AD through phenotype screening. Based on this platform, Professor Yi Zhong discovered the "active forgetting biological mechanism" affecting memory in 2010 and published the research findings in a well-known academic journal.CellAbove, it has become a potential new pathway for the treatment of Alzheimer's disease. According to the official website of the Chinese Drug Clinical Trial Registration and Information Disclosure,Zhuo Kai BioCurrently underway50561 TabletsTwo Phase 2a Clinical Studies for the Treatment of Mild to Moderate Alzheimer's Disease.
Johnson & Johnson: posdinemab
Mechanism of Action: Anti-tau Protein Monoclonal Antibody
Clinical Development Phase in China: Phase 1
Posdinemab (JNJ-63733657 Injection) is a new Alzheimer's disease drug candidate in Johnson & Johnson's R&D pipeline, currently in Phase 2 clinical trials globally.It targets a hyperphosphorylated epitope in the middle region of the tau protein, and researchers hope this design will allow the antibody to bind only with pathogenic tau proteins, rather than withAll tau protein subtypes binding。Tau protein is a soluble protein in neurons that binds to microtubules. The deposition and spread of pathological tau protein in the brain are closely correlated with cognitive decline in AD patients.
November 2021, posdinemabApproved for clinical use in China, applicable toDelaying Cognitive Decline in Patients Diagnosed with Prodromal AD and Mild AD DementiaAccording to the official website of the Chinese Drug Clinical Trial Registration and Information Disclosure Platform, Johnson & Johnson has completed a Phase 1 clinical study of this product in China targeting healthy Chinese subjects.
Connem Biotech: CM383 Injection
Mechanism of Action: Monoclonal Antibody Targeting Aβ Protofibrils
Clinical Development Phase in China: Phase 1
CM383 Injection is a product developed by Keymab.Monoclonal Antibodies Targeting Aβ Protofibrils, which was launched in China this May forAlzheimer's DiseasePhase 1 clinical study. Currently, monoclonal antibody therapies targeting Aβ are referred to as "disease-modifying treatments," the core of which lies in their intervention in the pathogenic mechanisms of Alzheimer's disease.Targeted clearance of excessive Aβ protofibrils in patients' brains, addressing the problem from its "root cause" rather than merely alleviating or managing the symptoms.
Luye Pharma: LY03020Maleate Sustained-Release Tablets
Mechanism of Action: TAAR1/5-HT2CR Dual-Target Agonist
Clinical Development Phase in China: Phase 1
LPM787000048 Maleate Sustained-Release Tablets (LY03020) is developed by Luye Pharma based on the new molecular entity/new therapeutic entity technology platform, and is aTrace Amine-Associated Receptor 1 (TAAR1) and Serotonin 2C Receptor (5-HT2CR) Dual-Target Agonists: A New Generation of Antipsychotic Drugs. The product is designed forAlzheimer's Disease with Psychotic Disorders (ADP)The indications have been approved for clinical use in China. In August this year, the Phase 1 clinical study of single-dose escalation for this product has been registered and initiated.
According to a previous press release by Luye Pharma, the dual-target mechanism of TAAR1 and 5-HT2CR, compared with existing antipsychotic drugs, can improve efficacy and reduce adverse reactions, with the potential to decrease side effects such as extrapyramidal symptoms (EPS) and metabolic syndrome. Preclinical studies have shown that this product can significantly improve both positive and negative symptoms of ADP.
Quattro Di Bio: QD202
Mechanism of Action: Synaptic Function Modulation
Clinical Development Phase in China: Phase 1
QD202 isA Class 1 new chemical drug under research by Kuaite Di Biotechnology, proposedFor treatmentMild, Moderate Alzheimer's Disease, which has currently initiated Phase 1 clinical research in China. Quattro Diagnostics Bio is committed to the diagnosis of neurodegenerative diseases and the research and development of innovative drugs. The founding team of the company has been deeply engaged in the research of neurodegenerative diseases for more than 20 years, especially inSynaptic Transmission and Cognitive FunctionResearch with extensive experience.QD202 isWith synaptic function regulationA product,ItBy increasing neurotransmitter release and enhancing lysosomal function, thereby achieving the therapeutic effect for AD.At the same time, the relevant mechanism also has the potential for developing drugs targeting post-stroke cognitive impairment.
Brayn Pharma: BrAD-R13
Mechanism of Action: Small Molecule TrkB Receptor Agonist
Clinical Development Phase in China: Phase 1
According to the press release from BrainRx Pharmaceuticals, BrAD-R13 is a Class 1 innovative drug under research by the company, and its target mechanism isNeuroprotection and regulation of the brain-derived neurotrophic factor BDNF-TrkB signaling pathway, and inhibition of asparagine endopeptidase (AEP)-involved pathogenic protein cleavage in various central nervous system (CNS) diseases.. The target mechanism of this product has been validated in various animal models, and relevant literature has been published inNature、CellThe series of publications, and preclinical studies have shown that BrAD-R13 has good safety. Subsequently, the development for multiple CNS indications such as Alzheimer's disease and Parkinson's disease can be gradually carried out. This product has been approved for clinical trials in the United States and China and is intended to be developed for the treatment of mild to moderate Alzheimer's disease. Currently, the phase 1 clinical study of this product has been registered and initiated.
Xinhua Pharmaceutical:OAB-14 Dry Suspension
Mechanism of Action:Multi-target Mechanism for Clearing Aβ in the Brain
Clinical Development Phase in China: Phase 1
OAB-14 Dry Suspension, jointly developed by Xinhua Pharmaceutical and Shenyang Pharmaceutical University, is intended for the treatment of mild to moderate Alzheimer's disease (AD).According to the announcement released by Xinhua Pharmaceutical in August this year, OAB-14 has currently completed Phase 1 clinical trial research, achieved the expected goals, and is planned to enter Phase 2 drug clinical research.OAB-14 is a novel anti-AD candidate drug with a completely new mechanism of action.Its role is mainly related to the clearance of Aβ in the brain, and also associated with multi-target mechanisms such as central anti-inflammation, antioxidation, and inhibition of neuronal apoptosis.Studies have shown that OAB-14 can significantly reduce β-amyloid deposition in the brain, decrease excessive phosphorylation of Tau protein, and protect the structure and function of cortical and hippocampal neurons and synapses.
Moreover, it is worth mentioning that globally, based on a deeper understanding of the pathogenesis of aging and Alzheimer's disease, the existing R&D pipeline is no longer solely focused on Aβ and tau proteins but instead exhibits a variety of innovative targets or mechanisms of action, such asIncrease magnesium ion levels in synapses, 5-HT6 receptor antagonist, inhibitor of neurotoxic aggregate protein transfer, restore FLNA protein conformation and function, induce chronic mild ketosisEtc.
Nevertheless, Alzheimer's diseaseIt remains a complex and challenging disease, and the search for safer and more effective treatments is still a long and arduous process.We look forward to continuous investment in scientific research and innovation in the industry, which can bring better options to patients and change their lives.
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