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Eisai/Bogen second Alzheimer’s drug has positive Phase 3 clinical results
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Eisai/Bogen second Alzheimer’s drug has positive Phase 3 clinical results, and is expected to be launched next year.
According to the World Health Organization, more than 55 million people worldwide suffer from Alzheimer’s disease (AD) , and it is estimated that by 2050, the number of patients may increase to 140 million.
As the most common neurodegenerative disease, patients with Alzheimer’s disease have clinical symptoms such as cognitive impairment, memory imbalance and abnormal behavior. social and economic burden.
At this stage, the pathogenesis of Alzheimer’s disease is still inconclusive, and the mainstream view is that its pathogenesis is caused by the massive death of neurons caused by the deposition of β-amyloid. Clinically, the difficulty of drug development lies in its complex pathology. So far, there is still no specific drug for Alzheimer’s disease .
On September 28, Eisai and Biogen jointly announced that the results of the Phase III clinical trial of their developed Alzheimer’s disease drug (Lecanemab) were positive : the disease progression slowed down during the 18-month treatment cycle. 27%.
It is worth mentioning that this is the first drug in the world that can still significantly inhibit the progression of Alzheimer’s disease in the final clinical trial stage.
Cognitive decline slowed by 27%: Clinical data provide strong support for amyloid hypothesis
It is understood that Lecanemab is a humanized monoclonal antibody jointly developed and commercialized by Eisai and Biogen for the treatment of early Alzheimer’s disease. It mainly targets various aggregates of beta amyloid, including Oligomers, fibrils and fibers, etc.
In June last year, the FDA granted Breakthrough Therapy Designation to Lecanemab .
In September last year, Eisai and Biogen submitted a Biologics License Application (BLA) to the FDA based on the clinical, biomarker and safety data of lecanemab in a Phase IIb clinical trial study .
It is understood that the phase IIb clinical trial of lecanemab drug recruited 856 patients with early Alzheimer’s disease to study the effect of lecanemab treatment on reducing beta-amyloid protein and cognitive decline, and the results showed that under the treatment of the drug, The patient’s brain β-amyloid plaques continued to decrease, which had a certain symptom relief effect.
At the same time, a confirmatory phase III clinical trial called “Clarity AD” is also underway, and the FDA agrees that the results of the Clarity AD trial can be used as evidence to verify the clinical efficacy of lecanemab.
In December last year, the drug lecanemab received the FDA’s fast track application; in July this year, the FDA granted the drug lecanemab priority review.
A few days ago, the two companies jointly announced that the Phase III clinical trial of lecanemab in the treatment of Alzheimer’s disease achieved the primary endpoint and all secondary endpoints.
The positive clinical trial results not only increase the chances of this drug being approved for marketing, but also bring good news to the majority of Alzheimer’s patients.
It is reported that this confirmatory phase III clinical trial study called Clarity AD enrolled 1795 patients with early Alzheimer’s disease, which is a placebo-controlled, double-blind, parallel group randomized clinical trial study, all patients were Randomized into lecanemab group and placebo group, among which, lecanemab group received 10 mg/kg of the drug every two weeks.
According to published Phase III clinical data, tested using the CDR-SB (Clinical Dementia Rating-Sum) , Lecanemab resulted in cognitive decline in patients with early Alzheimer’s disease compared to placebo after 18 months of treatment The speed slowed down by 27% , with a p value of only 0.00005, which was statistically significant and met the primary endpoint of the phase III clinical trial.
At the same time, all secondary endpoints also achieved significant differences with p-values less than 0.01.
The CDR-SB is a numerical scale used to quantify the various severity of Alzheimer’s disease symptoms, and is also used as an important indicator for evaluating the efficacy of early-stage Alzheimer’s disease treatments.
Professor Gregory Jicha
“Currently, we are seeing from the results of the Phase III clinical trial that the rate of cognitive decline in early-stage patients after treatment is reduced by an overall 27%, which corresponds to an ‘extended quality of life or reduced disease state’ of about eight months.” “Just as we did groundbreaking research in breast cancer back in the 1970s, we have now achieved a breakthrough in cancer,” said Gregory Jicha , Principal Investigator of the clinical trial and chair of the Department of Neurology at the University of Kentucky School of Medicine . We have come a long way in the same way that we can achieve this goal in the field of Alzheimer’s disease treatment, and this is just the beginning,” he added.
In addition, the Phase III clinical data show that the degree of β-amyloid reduction is significantly correlated with ADCOMS (Alzheimer’s Disease Composite Score) , CDR-SB (Clinical Dementia Rating-Sum), and ADAS-cog ( Alzheimer’s Disease Rating-Sum).
The Alzheimer’s Disease Assessment Scale-Cognitive Subscale) was associated with slower clinical decline, which also provided strong support for the beta-amyloid hypothesis of Alzheimer’s disease pathogenesis.
In terms of safety, the overall incidence of amyloid-related imaging abnormal edema/effusion (ARIA-E) and cerebral microbleeds, cerebral hemorrhage, and superficial siderosis (ARIA-H) in the lecanemab arm was 21.3% , 9.3% of patients in the placebo group. Overall, the incidence of ARIA (ARIA-E and ARIA-H) with lecanemab was as expected.
For now, the two companies have only disclosed some details of the results of the phase III clinical trial study, and more detailed results are planned to be fully presented at the Alzheimer’s Disease Summit on November 29.
Regarding the results of this phase III clinical trial, the Alzheimer’s Disease International (ADI) called the positive data of the trial ” the most encouraging results in clinical trials for the treatment of Alzheimer’s disease to date .”
“Alzheimer’s disease is not only a huge disaster for patients and their families, but also has a large number of negative impacts on society, such as reduced productivity, increased social costs and disease-related anxiety. Treating and curing Alzheimer’s disease is not only for patients. Individuals will also have a positive impact on society as a whole. The results of a phase III clinical trial of the drug Lecanemab support the beta-amyloid hypothesis—the abnormal accumulation of beta-amyloid in the brains of patients is central to the pathogenesis of Alzheimer’s disease One of the reasons,” said Eisai CEO Haruo Naito .
“The results of the phase III clinical trial we announced today have given new hope to the majority of patients.
If the drug Lecanemab is successfully approved for marketing, it can help more patients with early Alzheimer’s disease to slow down the deterioration of their disease, which can be said to be of great importance. Clinical significance.
In addition, we also thank the many clinical trial participants and researchers for their tireless efforts, and we believe that with our joint efforts, we will eventually overcome this global disease.” said Michel Vounatsos , CEO of Biogen .
The development of new drugs for Alzheimer’s disease is long and difficult: Early diagnosis and early screening are the key
The development of new drugs for Alzheimer’s disease is a recognized world problem.
Setbacks in the field of Alzheimer’s disease drug research and development have long been a common situation in the industry.
According to data from the American Drug Manufacturing and Research and Development Association, the current global total investment in Alzheimer’s disease research and development exceeds $600 billion, and the number of failed clinical drugs has reached 600 billion.
There are more than 300 kinds, and the failure rate is as high as 99.6% .
Because the pathogenesis of Alzheimer’s disease is very complex, up to now, the medical community has not completely solved its pathogenesis.
There are two mainstream hypotheses, one is the abnormal deposition of β-amyloid outside nerve cells, and the other is tau Abnormalities in the protein lead to the formation of neurofibrillary tangles.
In response to these two breakthroughs, international pharmaceutical giants, including Eisai, Biogen, Pfizer, Johnson & Johnson, and Eli Lilly, have invested a lot of human capital to develop therapeutic drugs in recent years, but they have not achieved breakthrough results.
In 2012, Pfizer and Johnson & Johnson announced that they would stop the development of the Alzheimer’s disease drug Bapineuzumab; in 2018, Eli Lilly and AstraZeneca announced that they would stop the phase III clinical trial of the oral inhibitor Lanabecestat for Alzheimer’s disease.
Today, the most popular and controversial Alzheimer’s disease treatment drug is the first drug jointly developed by Eisai and Biogen, Aducanumab (trade name Aduhelm, aducanumab) , which was launched in June last year.
Approved by the FDA, it is the first new antibody drug approved for the treatment of Alzheimer’s disease based on the β-amyloid hypothesis in the past 20 years.
However, many people in the industry believed that the clinical efficacy of Aducanumab The data is insufficient to support its approval for marketing.
Subsequently, the drug encountered a series of setbacks such as restricted use, dismal sales, and the disbandment of the R&D team.
The continuous blows led to Aducanumab falling into the abyss, and at the same time, the development of Alzheimer’s disease drugs became a “bottomless pit”, and the market prospect was worrying.
Eisai and Biogen continued to launch their second Alzheimer’s disease treatment drug, Lecanemab, and achieved positive results in Phase III clinical trials.
In terms of data, Lecanemab has outperformed its two main competitors at this stage, Donanemab developed by Eli Lilly and Gantenerumab developed by Roche .
It is understood that in June last year, the Alzheimer’s disease drug Donanemab developed by Eli Lilly was granted a breakthrough therapy designation by the FDA, which is an antibody drug targeting N3pG-modified beta-amyloid protein.
Eli Lilly announced that the application for clinical trials of Donanemab injection has been approved by the China National Medical Products Administration (NMPA);
and Roche’s Gantenerumab drug is also based on the beta-amyloid hypothesis and is a humanized IgG1 monoclonal Antibodies, not long ago, announced a number of positive trial results at the Alzheimer’s Association International Summit.
After the “fiasco” of the first drug, Aducanumab, Eisai and Bojian continued to develop the second drug, Lecanemab, and achieved impressive data performance in Phase III clinical trials, further deepening the theory of the beta amyloid hypothesis, or Will encourage more companies to rejoin the Alzheimer’s disease drug development team .
The key to Alzheimer’s disease lies in early diagnosis and early screening. No matter what strategy is adopted, it should be carried out before clinical symptoms appear.
Early diagnosis is critical for curing or significantly slowing the progression of Alzheimer’s disease, because once clinical symptoms appear, many of the patient’s vital neuronal cells have degenerated and synaptic plasticity cannot be restored.
In fact, early diagnosis It is the most core and effective means to truly solve these neurodegenerative diseases. ”
4. https://www.prnewswire.com/news-releases/the-us-fda-accepts-and-grants-priority-review-for-eisais-biologics-license-application-of-lecanemab-for-early- alzheimers-disease-under-the-accelerated-approval-pathway-301580919.html
5. https://baike.baidu.com/item/%CE%B2-%E6%B7%80%E7%B2%89%E6%A0%B7%E8%9B%8B%E7%99%BD/ 1212967?fromtitle=A%CE%B2&fromid=1164296&fr=aladdin
Eisai/Bogen second Alzheimer’s drug has positive Phase 3 clinical results
(source:internet, reference only)