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How does the new drug work? Why was it approved? What are the features?
Written by | A koi
On January 6, 2023, the U.
S.
Food and Drug Administration (FDA) announced accelerated approval
of Lecanemab-irmb, a treatment for Alzheimer's disease (AD).
This is also the second drug approved by the FDA after adducumab to modify AD
.
How much is known about the pharmacological effects of neomonoclonal antibodies
The World Health Organization (WHO) predicts that there will be 139 million dementia patients worldwide in 2050, of which AD patients account for about 60%-70%
of the total.
The pathogenesis of AD is still inconclusive, but there are four main hypotheses
.
Among them, the amyloid plaque hypothesis based on β-amyloid protein (Aβ) and the tau protein hypothesis based on neuronal microkinesis are considered to be the key to pathogenicity, which can work together on nerve cells to cause neuronal function loss
.
Traditional AD therapies are designed to improve symptoms, including cholinesterase inhibitors and non-competitive NMDA receptor antagonists
.
Lencanetumab is a humanized IgG1 monoclonal antibody with high affinity bound to Aβ-soluble fibrils, which can delay the progression
of AD neuronal incapacitation by selectively binding to existing Aβ-soluble fibrils in AD patients.
It is recommended to start treatment
after confirmation of the presence of Aβ in patients with mild cognitive impairment or mild dementia.
The recommended dose is 10 mg/kg iv, bi-weekly infusion, single infusion duration of about 1 hour
.
Phase 3 clinical results were released recently,
The future of lencanetumab can be expected
A Phase 3 randomized controlled trial study that confirms the clinical benefits of the drug as an inflammatory study was earlier published in the New England Journal of Medicine (NEJM) called Clarity AD
.
The 18-month, multicenter, double-blind, phase 3 trial included a total of 1795 participants aged 50 to 90 years, of whom 898 were assigned to lencaemizumab and 897 to placebo
.
The investigators confirmed that amyloid by positron emission tomography (PET) or cerebrospinal fluid detection were all patients with early-stage AD (AD causes mild cognitive impairment or mild dementia).
Participants in the lencanetimab and comfort units received either intravenous lencanezumab (10 mg/kg of body weight every 2 weeks) or placebo
, respectively.
The primary endpoint was the sum of the scores on the Clinical Dementia Rating Scale at 18 months (CDR-SB; Range, 0~18, higher score indicates more severe impairment) change from baseline
.
Key secondary endpoints were changes in: amyloid burden on PET, AD assessment scale 14 cognitive subscales (ADAS-cog14; Range, 0~90; a higher score indicates a more severe disorder) score, AD composite score (ADCOMS; range, 0~1.
97; higher scores indicate more severe impairment) and AD Collaborative Study-Mild Cognitive Impairment Activities of Daily Living Scale (ADCS-MCI-ADL; Range, 0~53; a lower score indicates a more severe disorder) score
.
The mean CDR-SB score at baseline was consistent between the two groups, both of which were about 3.
2
.
The mean change in adjusted least squares relative to baseline at the end of the study was 1.
21 in the lencanezumab group and 1.
66 in the placebo group (difference, -0.
45; 95% CI, -0.
67~-0.
23; P<0.
001
).
In a substudy containing 698 participants, cerebral amyloid burden was reduced more in the lencaneizumab group than in the placebo group (difference, -59.
1 centiloids； 95% CI，-62.
6~-55.
6）
。
For the measures that were superior to the placebo group in the lencanezumab group, the mean difference between the groups relative to baseline was as follows: ADAS-cog14 score was -1.
44 (95% CI, -2.
27~-0.
61; p<0.
001) and ADCOMS was -0.
050 (95% CI, -0.
074~-0.
027; p<).
0.
001), ADCS-MCIADL score of 2.
0 (95% CI, 1.
2~2.
8; P<0.
001).
In terms of safety, lencanezumab caused infusion-related reactions in 26.
4% of participants and amyloid-related imaging abnormalities with edema or exudation in 12.
6% of participants.
Figure: Primary and key secondary endpoints
Overall, reductions in amyloid markers were observed in patients with early AD in the Lunkanai group at the end of the study, and reductions in cognitive and functional measures in restructured subjects were smaller than in the placebo group, and the effect was associated with
the occurrence of adverse events.
That said, drug use is expected to slow the progression of AD and delay the deterioration
of cognitive and memory function in patients.
However, since the participants are not currently included in the early or late stage of the disease, the possibility
of drug use can be explored in these two groups in the future.
What do overseas experts say?
Donna Wilcock, associate dean of biomedical sciences at the University of Kentucky, said the drug should be approved
.
The data supporting Leqembi's application is "reliable," she said, adding that the trial's results were "the best AD treatment she has seen in 25 years.
"
Maria Carrillo, chief scientific officer of the International AD Association, said widespread use of the drug could mean more patients recognizing their spouses, children and grandchildren
for a few more months.
Although lencaminemab is not a cure, anything that allows patients to spend more time with their family and other loved ones is valuable
.
In addition to being approved in the United States, the marketing application of lencanetumab injection was also submitted by the National Medical Products Administration of China on December 22, 2022, and the application has been accepted
.
It is expected that the drug will be approved as soon as possible in China and benefit more AD patients and their families
.
References:
[1] style="margin-bottom: 0px;white-space: normal;text-align: justify;line-height: 1.
6em;">[2] _msthash="273783" _msttexthash="14755533">[3]Lecanemab in Early Alzheimer’s Disease.
Retrieved Nov29,2022,from style="margin-bottom: 0px;white-space: normal;text-align: justify;line-height: 1.
6em;"> _mstmutation="1" _msthash="162191" _msttexthash="647540946">The web version of the doctor station is online, please scan the QR code below or click to read the original article, you can browse more neurological information 👇👇👇 without downloadingAudit expertReview Li TumingDeputy Chief Physician Responsible EditorMr.
Submission/Reprint/Business Cooperation | Add WeChat chenaff0911
Lu Li
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