"Eraser in the mind" Alzheimer's disease has a new drug!
On July 6, local time, the official website of the US Food and Drug Administration (FDA) announced that the accelerated approval of lencanemab (English name: lecanemab, English trade name: Leqembi) jointly developed by Eisai/Biogen for the treatment of Alzheimer's disease (AD) has been successfully converted to full approval, which is the first Alzheimer's disease drug to be fully approved by the FDA in 20 years.
The FDA fully approved lencademab for the treatment of AD
Lencaneizumab belongs to the β amyloid (Aβ) drug, and an imbalance in the production and clearance of Aβ is widely believed to be associated with the progression of Alzheimer's disease. In January this year, based on the results of the Phase IIb proof-of-concept clinical trial, the FDA approved lencanezumab for the treatment of AD based on the accelerated review channel.
In terms of price, according to the US "Time" and other media reports, the annual treatment cost of lencanezumab is 26,500 US dollars, which is about 52% cheaper than the previous FDA accelerated approval of adunamab, which is also an anti-Aβ drug.
In China, Eisai submitted a marketing application for lencanezumab to the NMPA in October 2022. On February 28, 2023, Eisai China announced that the drug has been included in the priority review and approval process by the NMPA, which is expected to shorten the review time. Regarding the progress of lencanezumab in China, on July 7, the surging news reporter contacted Eisai China, the other party did not disclose more information, only said: "We are also waiting for further news." ”
How effective is the first new FDA-approved drug for Alzheimer's disease?
According to the "World Alzheimer's Disease 2018 Report" released by the International Alzheimer's Association (ADI), there are currently at least 50 million dementia patients in the world, and it is expected to reach 152 million by 2050, of which about 60%-70% are Alzheimer's disease patients.
People with Alzheimer's disease (AD) have impaired thinking, memory, and independence, and some describe them as having an eraser in their head, which not only affects quality of life, but even leads to death, and the FDA calls it a "devastating disease."
β amyloid-β (Aβ) is the pathogenesis of Alzheimer's disease that is currently recognized in the industry, and the approved lencanezumab revolves around this mechanism.
Source: Eisai China WeChat public account
As early as June 2021, the FDA accelerated the approval of aducanumab developed by Biogen for the treatment of early-stage Alzheimer's disease, which was then called the first new treatment approved for Alzheimer's disease since 2003. However, Aducanumab faced more skepticism after it was approved.
One of the reasons for the skepticism was that in November 2020, prior to FDA approval, FDA external advisory committee experts overwhelmingly voted against approval of the drug. Shortly after the drug was approved, three experts from the FDA's Peripheral and Central Nervous System Advisory Committee announced their withdrawal from the advisory committee in order to express their dissatisfaction with the approval.
Compared with adunazumab, the approved lencademumab was approved this time because of solid data support, and there was less controversy. On June 9, the FDA's Advisory Committee on Peripheral and CNS Drugs voted 6-0 in favor of the decision to fully approve lencanezumab. The FDA's full approval of lencanezumab is based on a Phase III clinical trial, Study 301, and FDA officials commented: "This confirmatory study confirms that it is a safe and effective treatment for Alzheimer's disease patients."
In November 2022, Eisai and Biogen announced data from another Phase 3 pivotal clinical trial, CLARITY study, showing a 27% clinical decline in the Clinical Dementia Score Summary Scale (CDR-SB) compared with placebo at 18 months with lencanetumab, in addition, a secondary endpoint assessed by AD caregivers, the Alzheimer's Disease Collaborative Study Group – Mild Cognitive Impairment – Ability to Live Scale Score (ADCSMCI-ADL) showed a significant statistical benefit of 37%.
For 27% of the data, foreign media reported that this is a modest but statistically significant result.
The annual cost is $26,500, which is about 52% cheaper than adunab
For Alzheimer's patients and their families, the emergence of new drugs gives them hope, but at the same time the issue of access to medicines cannot be ignored.
In terms of price, the annual treatment cost of adunamomab is 56,000 US dollars, and Biogen has promised that it will not raise the price in the next four years. However, due to the controversy over the efficacy of the drug, following stakeholder input and peer-reviewed documents, the Centers for Medicare and Medicaid Services (CMS) has stipulated that "for anti-Aβ monoclonal antibodies, CMS will only reimburse Medicare covered patients who participate in FDA or National Institutes of Health (NIH)-approved clinical trials, subject to accelerated FDA approval."
According to media reports such as Time Magazine, the annual treatment cost of lencanezumab is $26,500, which is about 52% cheaper than adunazumab.
Although the price has fallen, the accessibility of this drug still faces challenges. According to TIME, CMS said it will only be reimbursed outside of research after the drug has received full FDA approval and people are registered. As for CMS's decision to require registration, the report quoted some experts as saying it may be a more practical goal, which is to limit spending on the first effective Alzheimer's disease treatment.
Regarding the registration requirements, Eisai China issued a press release on July 7 that it is pleased that Medicare will pay for this important therapy for the right amount of patients, which will promote more medical institutions in the United States to reimburse and use the drug.
In China, lencanezumab has been included in the priority review. On July 7, the family of Alzheimer's disease patients told the surging news reporter that they look forward to this drug entering China as soon as possible, but they don't know which year it will be realized.
Eli Lilly, Hengrui, Xiansheng... Who will continue to clash with the "black hole of pharmaceutical R&D"?
The huge demand for Alzheimer's disease has attracted many pharmaceutical companies, but even multinational pharmaceutical giants are inevitably failing, such as in 2012, Pfizer, Johnson & Johnson and others announced the suspension of the research and development of Alzheimer's disease drug Bapinuezumab; In June 2018, Eli Lilly announced that it and AstraZeneca were discontinuing the global Phase 3 clinical trial of Lanabecestat, an oral β secretase lyase (BACE) inhibitor, for the treatment of Alzheimer's disease.
Repeatedly defeated, the research and development of Alzheimer's drugs was once called the "black hole of pharmaceutical research and development". The good news is that in recent years, in addition to the above two drugs, there have also been positive developments in drugs, and the forerunner is Eli Lilly.
Data from the study of the Lilly Alzheimer's drug Donanemab
On May 4 this year, Eli Lilly announced that its Alzheimer's drug donanemab had positive results in a Phase 3 clinical study of TRAILBLAZER-ALZ 2, which enrolled 1736 subjects, and the final primary endpoint indicator (iADRS) showed that donanemab delayed cognitive decline by up to 35%, and another important key secondary endpoint (clinical dementia score, CDR-SB) showed a 36% delayed decline in donanemab after 18 months. This is higher than Eisai/Biogen's 27% of lencaemab.
The results of the above trial also showed that nearly half (47%) of Donanemab subjects (29% in the placebo group) did not show clinical progress after 1 year of use. The phase 3 trial met the primary endpoint and all secondary endpoints assessing cognitive and functional decline. Compared with placebo, donanemab slowed clinical decline by up to 35% and the rate of decline in daily living abilities by 40%.
Donanemab is also an anti-Aβ monoclonal antibody, and the above data is recognized, although it is worth noting its safety concerns. Eli Lilly mentioned that the incidence of severe amyloid-associated imaging abnormalities (ARIA) was 1.6% in this study, including two subjects who died due to ARIA and another who died after a serious ARIA event.
It is worth noting that in China, Eli Lilly Donanemab has conducted an international multi-center phase III clinical study to evaluate its safety and efficacy in the treatment of early symptomatic Alzheimer's disease.
Clinical study of semeglutide on AD
Interestingly, this year's GLP-1 class drug semegglutide also has indications for Alzheimer's disease in research. In November 2021, Novo Nordisk has initiated a randomized, double-blind, placebo-controlled, Phase 3 clinical trial in China to study the efficacy and safety of oral sermeglutide in subjects with early-stage Alzheimer's disease. Novo Nordisk and Eli Lilly are fiercely competitive rivals in the GLP-1 weight loss space. The above information is still available on the website, and the status of the experiment is Ongoing.
Or failure, or success, Alzheimer's disease-related research has not gone in vain, and at present, the field still attracts pharmaceutical companies to continue to increase their weight. In April, Takeda and biotech company Treventis Corporation announced a collaboration and licensing agreement to jointly research, develop and commercialize small molecule drugs targeting Tau, a key protein for Alzheimer's disease (AD), for up to $372.5 million.
Domestically, Green Valley Pharmaceutical's mannat sodium capsules have long been approved for the treatment of Alzheimer's disease, and entered the national medical insurance catalog through medical insurance negotiations at the end of 2021, and the price was reduced to 296 yuan per box. However, the drug still faces various controversies today.
Some domestic AD related clinical trials
From the perspective of trials, the surging news reporter can search for 11 studies on Alzheimer's disease on the Chinese drug clinical trial registration and information disclosure platform, but most of them are traditional drugs to relieve AD symptoms such as memantine hydrochloride sustained-release capsules and mecobiline hydrochloride tablets.
Of course, there are also companies that are actively deploying new treatments for Alzheimer's. On March 21 this year, Hengrui Pharmaceutical (600276) announced that its subsidiary Shanghai Hengrui Pharmaceutical Co., Ltd. introduced that the phase Ib clinical trial of the company's self-developed anti-Aβ monoclonal antibody SHR-1707 injection for the treatment of early Alzheimer's disease completed the enrollment and administration of the first patient in the First Affiliated Hospital of University of Science and Technology of China.
In February 2022, Simcere Pharmaceutical (2096) announced that its clinical trial application for oral small molecule drug SIM0408 (PQ912, varoglutamstat) was approved by the Food and Drug Administration for the treatment of mild cognitive impairment (MCI) or mild dementia caused by Alzheimer's disease (AD). This oral drug was acquired by Simcere Pharma from Vivoryon in June 2021, and this cooperation of more than US$500 million gives Simcere Pharmaceutical the rights to develop and commercialize two drugs for the treatment of neurotoxic amyloid N3pE (pGlu-Abeta) Alzheimer's disease in Greater China, including SIM0408.