lecanemab phase 3 results

The baseline characteristics of both placebo and lecanemab groups are similar and well balanced. ARIA is an important adverse event of amyloid-lowering therapies that is critical to monitor and manage during treatment. Lecanemab is an investigational humanized monoclonal antibody for AD that is the result of a strategic research alliance between Eisai and BioArctic. But the clarity of the Clarity results with regard to efficacy, as evaluated by the CDR-SB, can not be debated, and that is a major advance for patients and the field. edema and hemorrhage combined, at 21.3 percent, and half that of aducanumab, suggest that lecanemab is relatively safer and easier to monitor even with twice per month infusions. Lecanemab is far better received by the market with total peak sales forecasted at up to $14 billion with Biogen sharing 50% of the . There is no guarantee that any investigational uses of such product will successfully gain health authority approval. Clarity AD is a clinical trial of lecanemab (development code: BAN2401), an investigational anti-amyloid beta (A) protofibril antibody for the treatment of mild cognitive impairment (MCI) due to. 1,795 participants of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild AD (collectively known as early AD) with confirmed presence of amyloid pathology in the brain in the global study, and an additional 111 subjects ongoing in China. CLARITY-AD may well be one of those revolutionary trials. For context, CDR-SB scores generally worsen by about 1.0 to 1.5 points per year in placebo groups, so the 0.45 point difference in an 18-month study would appear to be clinically important. BioArctic's Class B share is listed on Nasdaq Stockholm Mid Cap (ticker: BIOA B). In addition, the Phase 3 clinical study, AHEAD 3-45, for individuals with preclinical (asymptomatic) AD, meaning they are clinically normal and have intermediate or . Clarity AD was a global confirmatory Phase 3 placebo-controlled, double-blind, parallel-group, randomized study in 1,795 people with early AD. Lecanemab had a low rate of ARIA-E and ARIA-H, which is also gratifying. I hope the label will reflect that, and I anticipate Appropriate Use Recommendations for lecanemab reflecting these considerations will also be forthcoming. "This is the first time a therapeutic antibody has clearly changed the course of Alzheimer's disease. Lecanemab selectively binds to neutralize and eliminate soluble toxic A aggregates (protofibrils) that are thought to contribute to the neurodegenerative process in AD. 2016 Jun 13;53(4):1459-73. As we celebrate todays news, decades of research and expertise allow us to clearly see the path forward to a world where Alzheimers is a treatable, and even curable, disease, said Dr. Fillit. Alzheimers Dement. We must strive to do better. The lecanemab press release serves as great motivation to continue our search for additional mechanisms leading to AD, supplementing the critical progress being made. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. I expect the CDR will fast become one of the most talked-about measures of 2023. Keeping these factors in view, it is worth knowing about the ARIA-E score or autoimmune complications, particularly in patients carrying APOE4 allele. Phase 3 results showed it slowed patients' cognitive decline by 27% compared to a placebo after 18 months, greatly raising its chances of approval. 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On behalf of the more than 6 million Americans living with Alzheimer's disease and their families, the Alzheimer's Association enthusiastically welcomes the positive topline data reported today by . Lecanemab Confirmatory Phase 3 CLARITY AD Study Met Primary Endpoint, Showing Highly Statistically Significant Reduction Of Clinical Decline In Large Global Clinical Study Of 1,795 Participants With Early Alzheimer's Disease In the Clarity study, incidence of ARIA-E was 12.5 percent in patients treated with lecanemab compared to 1.7 percent of patients treated with placebo. 6. These statements are based on Biogen's current beliefs and expectations and speak only as of the date of this news release. We can only hope that the benefit is durable and could grow with time. But still, life-threatening ARIA and death are associated with lecanemab as they are with aducanumab. But that benefit is still limited. What the field needed was a clearly positive result from a trial completed and conducted per protocol, Gil Rabinovici at the University of California, San Francisco, wrote to Alzforum. Eisai and Biogen reported that the primary outcome was highly statistically significant at p=0.00005, and that secondary outcomes, comprising the ADAS-Cog14, ADCOMS, and ADCS MCI Activities of Daily Living, were all below p=0.01. Microbiology & Infectious Diseases. We may see larger, reasonable, and reliable CDR-SB effects approaching a clinically meaningful -0.9 difference or beyond in relevant subgroups. I am concerned that these apparently encouraging results will not withstand rigorous analysis, as has been the case with other anti-amyloid approaches, as demonstrated by a recent negative meta-analysis (Ackley et al., 2021). In July 2022, the U.S. Food and Drug Administration (FDA) accepted Eisai's Biologics License Application (BLA) for lecanemab under the Accelerated Approval Pathway and granted Priority Review. How did E4 carriers respond? 4. Biogen Safe Harbor Of course, I am looking forward to seeing the primary data at CTAD 2022. This is the website of Eisai Inc., a US company. 1,795 participants of mild cognitive impairment (MCI) due to AD and mild AD (collectively known as early AD) with confirmed presence of amyloid pathology in the brain in the global study, and an additional 111 subjects ongoing in China. Cant wait to see the data:). Eisai will discuss this data with regulatory authorities in the U.S., Japan and Europe with the aim to file for traditional approval in the US and for marketing authorization applications in Japan and Europe by the end of Eisai's FY2022, which ends March 31, 2023. It is important to learn what the mean difference and standardized effect size is on the ADAS-cog14, because this is the only neuropsychological composite measure in the trial. Lecanemab treatment met the primary endpoint and reduced clinical decline on the global cognitive and functional scale, Clinical Dementia Rating-Sum of Boxes (CDR-SB) compared with placebo at 18 months by 27%, which represents a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of Intent-to-treat (ITT) population. These organisms have been implicated many times in the pathogenesis of AD. The results support full approval of lecanemab in early AD, and provide support for the amyloid therapeutic hypothesis (and for the FDA accelerated approval of aducanumab on the basis of amyloid reduction). This being said, there is not much to argue about in the press release aside from the statement that these clinical trial results prove the amyloid hypothesis. As someone who studies disease mechanisms, Im not sure this study informs questions of AD etiology. Synaptogenix Welcomes Lecanemab Phase 3 Trial Results. We will learn much from detailed analysis of the biomarker data, as well as genetic and safety data. The press release indicating that lecanemab hit its primary and secondary endpoints in slowing cognitive decline in very mild to mild AD is incredibly exciting. We are optimistic about the future as many of these drugs are in development, with 75% of drugs in the pipeline now targeting non-amyloid pathways of neurodegeneration.. While there is need to withhold judgment until we can see the data, this is excellent news. The results are very consistent with the previously published data of the Phase 2 trial, and will give a green light toward the regulatory approval and, hopefully, insurance coverage. BMJ. Microbiol Infect Dis. Time is brain. Biogen does not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise. This pattern of clear-cut clinical benefits, and a manageable adverse event profile, is what the field has hoped for. Eisai and Biogen yesterday announced positive topline results from the Phase 3 Clarity trial of their anti-amyloid antibody lecanemab. Neuron. That said, the trigger of the disease means that amyloid triggers a long preclinical cellular phase (De Strooper and Karran, 2016) that stands between the first appearance of the plaques and the clinical outcome of dementia. Nonetheless, we appreciate the top-line results of lecanemab as the beginning of a new era in the history of AD therapeutics and research. Or perhaps that any reliably observed difference on any clinical scale is clinically meaningful. Antibodies for prevention and treatment of infectious disease. Lecanemab treatment reportedly reduced clinical decline on the CDR-SB by 27 percent compared with placebo at 18 months. Brain amyloid has been seen as a primitive defense against brain infectious agents invading the brain (Moir et al., 2018). 2022 Jan;19(1):209-227. However, if we use the analogy to the war on cancer, a battle has finally been won, but the war is far from over. There remain a number of important tasks to prepare for the implementation of the initial DMT in dementia clinical practice in Japan. Currently, lecanemab is being developed as the only anti- A antibody that can be used for the treatment of early AD without the need for titration. All key secondary endpoints were also met with highly statistically significant results compared with placebo (p<0.01). Twenty-seven percent slowing of rate of decline is simply a start. The incidence of ARIA-E, a major adverse effect of amyloid-removing antibody drugs, was 12.5 percent, which was relatively modest compared to those reported with similar antibody drugs. 2013 Aug;126(4):473-82. Eisai recently announced positive topline results from Clarity AD, a phase 3 study evaluating the safety and effectiveness of lecanemab, an investigational anti-amyloid beta (A) protofibril . PubMed. Clinical trial results for lecanemab . J Alzheimers Dis. While other drugs have achieved promising results, and aducanumab was given accelerated approval by FDA in 2021, this clearly positive Phase 3 study represents a landmark for the field. In March 2014, Eisai and Biogen entered into a joint development and commercialization agreement for lecanemab. The total score of the six areas is the score of CDR-SB, and CDR-SB is also used as an appropriate item for evaluating the effectiveness of therapeutic drugs targeting the early stages of AD. At first glance from the release, it sounds like there is clinically meaningful lessening of cognitive decline, suggesting that the antibody will be helpful as a treatment. You should not place undue reliance on these statements or the scientific data presented. If the Clarity AD data is as advertised, not only will it pave the way for full FDA approval of lecanemab, it may tip the scales in favor of plaque-clearing antibodies, suggesting that this class of drugs does in fact work as it did in the Phase 2 studies and EMERGE. Eisai is responsible for the clinical development, application for market approval and commercialization of the products for Alzheimer's disease. TOKYO and CAMBRIDGE, Mass., Sept. 27, 2022 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Michel Vounatsos, "Biogen") announced positive topline results from Eisai's large global Phase 3 confirmatory Clarity AD clinical trial oflecanemab (development code: BAN2401), an investigational anti-amyloid beta (A) protofibril antibody for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild AD(collectively known as early AD) with confirmed presence of amyloid pathology in the brain. If, and when, the drug is approved by the FDA, I believe that initially we should be conservative, administering the treatment to patients who, by and large, would have met the inclusion/exclusion criteria for the trial, and then carefully monitoring for ARIA on a similar MRI schedule to that in the clinical trial. In March 2022, Eisai began submitting application data, with the exception of Clarity AD data, to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) under the prior assessment consultation system with the aim of obtaining early approval for lecanemab so that people living with early AD may have access to the therapy as soon as possible. I hope that the price setting remains reasonable and not $50,000, as Aducanumab initially. In an effort to secure traditional FDA approval for lecanemab as soon as possible, Eisai submitted the BLA through the FDA's Accelerated Approval Pathway so that the agency could complete its review of all lecanemab data with the exception of the data from the confirmatory Clarity AD study. I am therefore skeptical of any "cutoff" set in the literature, and would discourage regulatory bodies from basing decisions on such cutoffs. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. clinical study (Study 201). What is the role of amyloids influence on tau? Synaptogenix Welcomes Lecanemab Phase 3 Trial Results. The total incidence of ARIA (ARIA-E and/or ARIA-H) was 21.3% in the lecanemab group and 9.3% in the placebo group. The Clarity AD results fully meet all our expectations, both in terms of highly statistical significance and in the consistency over primary and all key secondary endpoints. However, amyloid-clearing drugs will provide an incremental benefit at best and there is still a pressing need for the next generation of drugs focused on other targets based on our knowledge of the biology of aging. We published that anti-oligomeric monoclonal antibodies significantly reduce amyloid load and improve cognition. ADAS-cog has been used in trials for earlier stages of AD including MCI. Eisai believes these findings will create new horizons in the diagnosis and treatment of Alzheimer's disease as well as further activate innovation for new treatment options. Based on the top-line results, it appears that there was a statistically significant benefit from lecanemab, a monoclonal antibody targeting protofibril A, in slowing progression of cognitive impairment in early Alzheimer's disease. I would first want more information on efficacy. The topline results of lecanemab Phase 3 Clarity AD unequivocally showed that the study achieved the primary endpoint, i.e., statistically significant difference in the 18-months change from baseline of CDR-SB by 27 percent, by the administration of an anti-A humanized monoclonal IgG1 antibody that has a high affinity to A protofibrils in vitro and has been shown to robustly remove brain amyloid deposits in early phase human trials. I imagine there will be some speculation regarding to what extent side effects contributed to unblinding and in general affected the final analyzed datasets and trial endpoints. . In March 2022, Eisai began submitting application data, with the exception of Clarity AD data, to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) under the prior assessment consultation system with the aim of obtaining early approval for lecanemab so that people living with early AD may have access to the therapy as soon as possible. The goal, which we are closer to than ever, is to develop a toolbox of novel biomarkers and effective treatments against a range of targets in the brain so physicians can zero in on the causes of each patients Alzheimers and tailor combinations to meet their individual needs, creating a precision medicine approach to the disease. This confirms the importance of A in disease pathogenesis and supports the idea that removing amyloid even before symptoms emerge has a chance to have an even greater effect, such as delaying the onset of clinical symptoms. More needs to be learned for lecanemab to find its place. Synaptogenix expecting data from its Phase 2 clinical trial of Bryostatin-1 for advanced Alzheimer's disease in fourth quarter 2022. The effect size is very small, which will undoubtedly create rigorous debate moving forward. About Lecanemab A45 will enroll 1,000 participants who have a positive amyloid PET scan. This release discusses investigational uses of an agent in development. 1CDR-SB is a numeric scale used to quantify the various severity of symptoms of dementia. The total score of the six areas is the score of CDR-SB, and CDR-SB is also used as an appropriate item for evaluating the effectiveness of therapeutic drugs targeting early stages of AD. The project portfolio is a combination of fully funded projects run in partnership with global pharmaceutical companies and innovative in-house projects with significant market and out-licensing potential. PubMed. Additionally, Eisai will present the Clarity AD study results on November 29, 2022, at the Clinical Trials on Alzheimer's Disease conference (CTAD) and publish the findings in a peer-reviewed medical journal. The incidence of symptomatic ARIA-E was 2.8% in the lecanemab group and 0.0% in the placebo group. About Eisai Co., Ltd. Furthermore, Eisai has initiated a lecanemab subcutaneous dosing Phase 1 study. In March 2021, Eisai completed enrollment of 1,795 patients with early Alzheimer's disease in our confirmatory Phase 3 Clarity AD clinical study. Synaptogenix expecting data from its Phase 2 clinical trial of Bryostatin-1 for advanced Alzheimer's disease in fourth quarter 2022. PubMed. About BioArctic ABBioArctic AB (publ) is a Swedish research-based biopharma company focusing on disease-modifying treatments for neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and ALS. The FDA has agreed that the results of Clarity AD can serve as the confirmatory study to verify the clinical benefit of lecanemab. The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), an adverse event associated with anti-amyloid antibodies, was 12.5% in the lecanemab group and 1.7% in the placebo group. All secondary study goals were met as well. Change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months, Change From Baseline in Amyloid Positron Emission Tomography (PET) using Centiloids, AD Assessment Scale - Cognitive Subscale 14 (ADAS-cog14*), AD Composite Score (ADCOMS**) and AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL***) at 18 months. My question would be: Would not an accurate diagnosis with CSF biomarker testing be useful for earlier detection and a diagnosis in the mild/moderate cognitively impaired patient and for the potential "caregivers" of that patient? Under this Concept (also known as human health care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. We want to thank the many patients who participated in this groundbreaking global study and want to acknowledge the clinical investigators who worked tirelessly to increase the enrollment of traditionally underrepresented populations. The data on lecanemab is certainly good news for the field, and finally some hope for those suffering from this terrible disease. Clarity AD is enrolling adults with early stage Alzheimer's, who show disease symptoms, in China. The trial, however, was planned from the get-go to be able to detect a difference of less than -0.40 with 90 percent power and was made large enough to do just that. I am pleased by the robustness of the top-line results and the likelihood of accelerated approval first, then regular approval. The Part B deductible also went up $30, to $233, from $203. The study is now in its extension phase. Environmental, Social and Governance (ESG), HVAC (Heating, Ventilation and Air-Conditioning), Machine Tools, Metalworking and Metallurgy, Aboriginal, First Nations & Native American. On its face, other things being equal and assuming a low risk of bias, the P value strongly suggests that the CDR-SB primary outcome is robust and not going to be overturned in sensitivity analyses. The low rates of ARIA reported here are also encouraging and will impact the risk/benefit decision-making among patients and clinicians. A3 will enroll 400 people with amyloid below the brain-wide threshold for positivity; they will receive 5 mg/kg titrating to 10 mg/kg BAN2401 or placebo every four weeks for 216 weeks, and their primary outcome will be change in brain amyloid PET at that time. There was no imbalance in isolated ARIA-H (i.e., ARIA-H in patients who did not also experience ARIA-E) between lecanemab (8.8%) and placebo (7.6%). BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early . This Phase 3 trial will test the effectiveness of the experimental drug Lecanemab as a possible treatment for Alzheimer's disease. Earlier trial results from lecanemab, donanemab, and aducanumab had linked plaque removal to slowing of cognitive decline, but the findings were often muddied by conflicting results or small sample size. The confirmatory Phase 3 study, Clarity AD, with lecanemab in early Alzheimer's disease is currently ongoing and Eisai expect to have the topline results by the end of September 2022. Developed originally by Lars Lannfelt of Sweden's Uppsala University, lecanemab, aka BAN2401, had shown a cognitive benefit in Phase 2 as well. Sep 28, 2022. All Rights Reserved. No one in the field should ever want any drug trial in AD to failthe unmet medical need is too large. The drug was tested in a group of 1,795 people with mild cognitive impairment or mild Alzheimer's. Compared to placebo, 18 months of biweekly lecanemab infusions led to a significantly lower rate of cognitive . No one will argue that we have a cure here, but it seems that lecanemab moves the needle, opening the door for future treatments, or combinations of molecular-specific treatments, that will be increasingly efficacious. ARIA is most commonly seen as temporary swelling/effusion (ARIA-E) in areas of the brain that usually resolves over time. Collaborations with universities are of great importance to the company together with its strategically important global partner Eisai in Alzheimer disease. 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