The gospel of “Su Daqiang”.
Recently, the State Food and Drug Administration official website announced that it has conditionally approved the mild to moderate Alzheimer’s disease drug manneth sodium capsule (GV-971), which is marketed by Shanghai Green. Valley Pharmaceutical Co., Ltd., Ocean University of China, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, joint research and development, the product name nine phase one ®.
It is reported that the mannite sodium capsule will be put into operation on November 7th, and will be put into the national channel before December 29th; from next year, post-marketing research will be carried out. Pudong New Area has provided 40 mu of land for industrialization. Construction started this year. If it can be completed in three years, it can satisfy the sales of 2 million patients.
Nine Issues One
In fact, before this, only five drugs that delayed the disease were approved for marketing worldwide, and the effects were not obvious. They only slightly improved the cognitive function of patients. In addition, since 2002, it has been 17 years. No new drugs were on the market and 86 drugs were terminated. Although there are controversies about unclear pharmacology and doubts about the test data, the approval of the Nine Phase One® can be said to fill the gap of 17 years of no new drug market in the field of Alzheimer’s disease (AD).
US FDA-approved AD treatments (Eight-point biographies )
Development of new AD drugs with repeated defeats and repeated defeats
Alzheimer disease (AD), commonly known as Alzheimer’s disease, is a persistent nerve with a slow onset and worsening over time.Dysfunction is a central nervous system degenerative disease.
All along, human anti-AD new drugs have extremely strong clinical needs. AD has approximately 50 million patients worldwide and is experiencing explosive growth, with an estimated 150 million people by 2050. According to statistics, one in three people worldwide is diagnosed with AD every 3 seconds. In China, Alzheimer’s disease patients have exceeded 10 million, ranking first in the world .
A US survey shows: taking care of patients takes a long time and lasts, 60 More than % of family members and nursing staff are affected by extreme emotional changes and mental stress, and one third of them have depression. All caregivers who care for Alzheimer’s disease have a negative impact on their own health, work, income and family finances. It is estimated that the cost of AD in the global society will be $1 trillion in 2018, and by 2030, this number will increase to $2 trillion – which is associated with this trillion-dollar anti-AD New Drug Market.
It is expected that any effective drug will grow into a blockbuster drug (with annual sales exceeding $1 billion). To date, global pharmaceutical companies have invested hundreds of billions of dollars in research and development.
Behind the heat, in fact, most of the new AD drug research has been overturned, even known as “the Everest in the pharmaceutical industry”. Data shows, Between 1998 and 2017, 146 Alzheimer’s drugs worldwide failed in clinical R&D centers, 40% died in early clinical stages, 39 % failed clinically in the mid-term and 18% failed in the later stages. Even if they are like Pfizer, Eli Lilly, Roche… They all have a long history and a brilliant and superior product, but in the face of AD, they are still “incapable of doing anything.”
Take Lolanetumab of Lilly’s company as an example. After three or three phases, it will still fail. There will be improvement in 40 weeks, but it will be invalid by 80 weeks. In the first half of this year, Biogen Eisai announced that due to the failure of Aducanumab’s research and development, they will abandon most of the Alzheimer’s disease research and development projects, which directly led to a 26% drop in Baijian’s share price and a market value loss of more than 15 billion US dollars.
Regarding the cause of failure, first of all, the pathogenesis of Alzheimer’s disease does not currently have a widely accepted theory. Aβ toxicity, Tau protein hyperphosphorylation, gene mutation, neurotransmitter depletion, cholinergic nerve damage, free radical damage, immune inflammatory damage, etc. are all considered to be associated with the pathogenesis of AD. In addition, AD is a chronic disease, and any clinical trial needs to persist for many years to see the results. In addition, there is currently no suitable animal model for the disease. All clinical trials have to be done in human volunteers, and the patient population is not homogenous. Under the existing new drug research and development system, there are not many companies that can eat it. the cost of.
Even so, due to the huge gaps in the market and the pressure of aging society, exploration of new drugs against Alzheimer’s disease and huge capital investment continue even if research and development are difficult..
According to the registration data of clinicaltrials.gov, giants such as Roche, Baijian, Janssen, Eli Lilly and Takeda are still there; in addition, this yearAcadia Pharmaceuticals is still Perform a third-stage HARMONY trial to evaluate the efficacy and safety of Pimavanserin in the treatment of hallucinations and delusions associated with dementia-related psychosis;Denali also works with Sanofi to perform DNL747 Alzheimer’s disease clinical Ib Period test.
New drug development is so difficult, what else can it do?
However, in any case, AD is still in the state of “lack of medical care”, and the effectiveness and reproducibility of various drugs can only alleviate the symptoms, eliminate the incentives, and have major side effects. And dependence, such as causing gastrointestinal nausea, vomiting symptoms, etc., so many patients simply “no medicine can cure.”
In this case, is there any other way to deal with AD?
Retrospective treatment of AD, the initial introduction of AD therapy is not a drug treatment, but a method called nostalgic therapy, that is, the treatment of patients by psychological suggestion. Clinical research findings, nostalgic therapy can effectively treat apathy and depression in patients with mild to moderate senile dementia.
Nostalgic-based products are currently available on the market, such as the US Smart Brain Aging has launched Brain U Online, a virtual online product similar to nostalgic therapy, which provides users with over 20,000 cognitive skills related to processing speed, memory and attention. The core of the exercise content. However, this treatment appears to be weak for patients who have developed severe AD symptoms.
The treatment of AD, in addition to innovative drugs and digital therapy, as well as the field of medical devices. For example, Korean start-ups Ybrain has launched a smart headband for treating AD, which is built-in. The sensor stimulates brain activity by emitting an electrical signal of 2 mA. The patient can effectively alleviate the symptoms of Alzheimer’s disease by using it for 30 minutes a day. In addition, in August last year, Dthera Sciences’ DTHR-ALZ obtained the FDA-approved breakthrough equipment certification To alleviate the agonistic and depressive symptoms of Alzheimer’s disease neurocognitive disorders.
Currently, stem cell therapy is in preclinical models of ADIt also shows good application prospects, but further research is needed. In addition, the Alzheimer’s disease vaccine also made a good voice. In June of this year, the New Mexico State University (UNM) developed the frontotemporal dementia (FTD) animal model rTg4510 (not an animal model of AD) that alleviates the pathology of pure Tau protein aggregation. However, the researchers also acknowledged that the successful development of the human AD vaccine may take at least another decade.
In recent years, surgery has also begun to try using deep brain power Stimulation (DBS) surgical treatment of AD has achieved initial clinical results, but it is still in a very early experimental stage, and it will take some time to go to clinical application.
The lack of medical care, predicting the best way to deal with AD
In summary, although AD disease treatment exploration has repeatedly achieved new results, but so far, we still can not talk about “cure”, or should hope for early detection to delay the onset of the disease. In other words, at this stage, early prevention and early diagnosis are the most effective ways for humans to fight Alzheimer’s disease.
How do you prevent it early? Department of Neurology, West Campus, West Campus, Huashan Hospital, Fudan UniversityProfessor Yu Jintai publicly stated , AD should also implement a three-level prevention strategy, primary prevention can be performed when the cognitive is normal and there is no pathological manifestation; secondary prevention can be implemented in the stage of cognitive normal/mild abnormality and pathological physiological marker change .
The means of prevention depend on the diagnosis, so early detection is of great significance for the prevention and control of Alzheimer’s disease. However, at present, the clinical pain points are still obvious in terms of diagnosis. For a long time, AD detection mainly uses lumbar puncture to extract cerebrospinal fluid. It detects Aβ amyloid and Tau protein. It needs to be injected with anesthetic beforehand. It also causes nerve pain after lumbar puncture, and it is expensive and difficult to be used by patients. Accepted (can be compared to colonoscopy).
Liver puncture extracts cerebrospinal fluid (Source: Oriental IC)
As for early diagnosis, there are four current methods, including computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). . The same problems are faced with early diagnosis of other diseases. Due to the high cost of equipment and the accuracy of qualified doctors, the above methods cannot be popularized.
However, in recent years, AI technology has begun to interveneAD early screening, and the corresponding products have also landed in hospitals. Like the UK’s Avalon AI, using deep learning technology to develop computer medical imaging diagnostic tools, the effective prediction accuracy has reached 75%; there are also Jason in China. Technology, Niu Nuo Technology, 铱硙铱硙, brain doctors and other companies are here to deploy, and products have been introduced one after another. Not only can they avoid the pain of invasive testing, but they can also generate quantitative results in a short period of time and improve screening efficiency.
At the level of molecular diagnosis, there are still results, and the most common one is mass spectrometry (Hauss Bio) and applications in gene sequencing; new methods are constantly being explored, such as March 2019, IBM Australia research team announced the development of an alternative to spinal fluid testing for AD, which uses blood for machine learning Test to determine the content of amyloid beta plaque in spinal fluid, the accuracy rate is 77%; August 2019 Researchers at the University of Washington School of Medicine have developed a method for diagnosing AD through blood tests, which can be found several years before the brain scans, and so on.
Extended reading
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