CAMBRIDGE, Mass., and TOKYO, Mar 22, 2022 - (JCN Newswire) - Eisai Co., Ltd. and Biogen Inc. announced today that the latest findings on lecanemab, an investigational anti-amyloid-beta (Abeta) protofibril antibody being developed for the treatment of early Alzheimer's disease (AD), were presented at the Abeta Targeted Therapies in AD 2 Symposium at the 2022 International Conference on Alzheimer's and Parkinson's Diseases (AD/PD) March 15-20 in Barcelona, Spain and virtually.

Four key symposium presentations explored how lecanemab's clinical efficacy data, overall amyloid-related imaging abnormality (ARIA) rates, biomarker relationships to clinical outcomes, potential dosing regimens, and administration have the potential to benefit people living with early AD.

1. Science of the Amyloid Cascade and Distinct Mechanism of Action (MoA) of Lecanemab

- BioArctic's Professor Lars Lannfelt presented the science of the amyloid cascade and studies evaluating lecanemab's distinct binding profile to antibodies created from patented sequences of two other clinical antibodies, aducanumab and gantenerumab. The three antibodies have different binding profiles to Abeta species. All three antibodies bind to fibrils, but with different selectivity. Lecanemab was the strongest Abeta binder and prefers protofibrils. Lecanemab's binding profile is critical to enriching our understanding of the features in clinical outcomes and safety. BioArctic has had a long-term collaboration with Eisai regarding the development and commercialization of drugs for the treatment of AD.

2. Key Trial Design Aspects and Clinical Outcomes of the Lecanemab Phase 2b (Study 201) Trial and Open-Label Extension (OLE) in Early AD

- Innovative Bayesian Adaptive Randomization Design and Dose Regimen-Finding Study with OLE - Study 201 (published by Eisai in Alz Res Therapy 13;21) was prospectively designed as a blinded 18-month study. To accelerate the development program, Eisai used a Bayesian adaptive design with a prespecified 12-month Bayesian primary endpoint in addition to the prespecified traditional analysis at the end of the 18-month treatment period. The OLE evaluated the long-term safety and tolerability of lecanemab and the effect of lecanemab on amyloid PET over 12 months of treatment, which looked at treatment naive patients (those on placebo during the core study) and those patients who had previously been treated with lecanemab, including earlier time points (3 and 6 months) than in the core phase (12 and 18 months). Eisai's study design provided the opportunity to explore the biomarker and clinical effects of stopping and restarting lecanemab across five years of disease trajectory.

- Rapid and Thorough Amyloid Clearance Correlates with Clinical Benefit - By using the Bayesian study design across a broad range of doses, researchers were able to efficiently and effectively identify the most effective dose, 10 mg/kg biweekly, to produce rapid and thorough amyloid clearance and potential clinical efficacy. Of the approximately 12 treatment-naive patients in the OLE (those who received placebo in the Core study), more than 40 percent were amyloid negative as early as 3 months and more than 80% were amyloid negative by 12 months as measured by PET image (visual read).(1) The OLE results are consistent with core phase results in which 65% were amyloid negative at 12 months(1) and 81% of participants were amyloid negative at 18 months as measured by PET image (visual read) in 161 subjects treated with 10 mg/kg biweekly dose. Robust amyloid reduction in those receiving lecanemab in the Core study was maintained while off-treatment over the Gap period. Despite the small number of participants in the OLE, findings help confirm the results from the Core study: lecanemab rapidly and thoroughly cleared amyloid plaque from the brain. Study 201 established 10 mg/kg biweekly as the most effective dose of lecanemab based on ADCOMS. Lecanemab could potentially be administered at 10mg/kg on the first day of treatment and continue at biweekly intervals without titration.

ARIA Incidence, Frequency, Severity and Modeling
ARIA-E is an important adverse event of amyloid-lowering therapies that is critical to monitor and manage during treatment.

Study 201 Core ARIA-E Rates
ARIA-E was observed in allele groups administered 10 mg/kg biweekly at the following rates: overall ApoE4 carriers 14.3% (7/49), ApoE4 carriers homozygous 50.0% (5/10), ApoE4 carriers heterozygous 5.1% (2/39) and ApoE4 non-carriers 8.0% (9/112). The overall ARIA-E rate in the Core study was 9.9% (16/161) of patients treated with lecanemab 10 mg/kg biweekly compared with 0.8% (2/245) of placebo patients.

Study 201 OLE ARIA-E Rates
Although ApoE carriers were underrepresented in the 10 mg/kg biweekly group in Study 201 Core, all participants entering Study 201 OLE (69.4% of whom were ApoE4 carriers) were treated with 10 mg/kg biweekly, and ARIA rates were consistent with those in the Core study. Forty-five participants who received placebo in the Core study joined the OLE. ARIA-E was observed in allele groups newly treated with 10 mg/kg biweekly in the OLE at the following rates: overall ApoE4 carriers 12.9% (4/31), ApE4 carriers homozygous 25.0% (1/4), ApoE4 carriers heterozygous 11.1% (3/27) and ApoE4 negative 0.0% (0/14). In the OLE study, overall ARIA-E rates were as follows: ApoE4 carriers 10.4% (13/125), ApoE4 carriers homozygous 14.3% (4/28), ApoE4 carriers heterozygous 9.3% (9/97) and ApoE4 non-carriers 1.8% (1/55).

Study 201 Core and OLE Pooled ARIA-E Rates
In the Core and the OLE, ARIA-E was observed in allele groups administered 10 mg/kg biweekly at the following rates: ApoE4 carriers 13.8% (11/80), ApoE4 carriers homozygous 42.9% (6/14), ApoE4 carriers heterozygous 7.6% (5/66) and ApoE non-carriers 7.1% (9/126). The overall ARIA- E rate was 9.7% (20/206) of patients treated with lecanemab 10 mg/kg biweekly.

ARIA-E Rates Frequency and Severity
In the Core study and OLE, the majority of ARIA-E events occurred within the first 3 months of treatment (75% [12/16]) and resolved within 4 months of onset. For the majority of patients, the radiographic severity was mild or moderate; severe radiographic severity was reported in 1.2% (2/161) of patients. The majority of ARIA-E was asymptomatic; with symptomatic ARIA-E reported in 1.9% (3/161) of patients. Symptoms reported in association with ARIA-E included headache, visual disturbance, confusion, aphasia. There has been a single case of ARIA-E associated with seizure in the Core study and OLE to date.

Exposure-Response Model Predicted and Observed ARIA-E vs. Cmax for APOE 4
The PK/PD exposure-ARIA-E model was developed from the Core study utilizing data from all doses and demonstrated that ARIA-E is driven primarily by Cmax. The ApoE4 genotype is a significant covariate in the model. The PK/PD model predicted ARIA-E by Cmax at the 10 mg/kg biweekly dose in the Core study by allele group as follows: ApoE4 carriers homozygous 22.5%, ApoE4 carriers heterozygous 6.8% and ApoE4 non-carriers 5.4%. In addition to the modeling predicting ARIA-E by Cmax in the Core study, it confirmed the observed ARIA-E in the OLE. Given the small data set for ApoE4 homozygous patients, this will be evaluated in Eisai's Phase 3 Clarity AD clinical trial.

ARIA-H Rates
In the Core study, the incidence was higher in ApoE4 homozygous carriers than in ApoE4 heterozygous carriers and non-carriers. ARIA-H was observed in 6.2% (10/161) of patients treated with lecanemab 10 mg/kg biweekly compared with 4.9% (12/245) of placebo patients. The rate of ARIA-H was higher in ApoE4 carriers (12.2% [6/49] vs placebo 5.2% [9/174]), than in ApoE 4 non- carriers (3.6% [4/112] vs placebo 4.2% [3/71]). All patients with microhemorrhage or superficial siderosis were asymptomatic. There has been one report of symptomatic cerebral macrohemorrhage. These data are hypothesis-generating and will be further evaluated in Clarity AD.

3. Phase 2b (Study 201) Lecanemab Early AD Study Biomarker Results, Correlations with Clinical Outcomes and Potential Less-Frequent Maintenance Dosing

- Abeta42/40 and P-Tau181 are plasma biomarkers that signal sequential changes in AD progression. Lecanemab has an effect on these plasma biomarkers as amyloid plaque reduction is related to soluble amyloid and P-Tau. Lecanemab has a dose- and time-dependent reduction of amyloid plaques with a correlated increase in plasma Abeta42/40 and a decrease in plasma P-Tau181. Changes in plasma Abeta42/40 and P-Tau18 also correlate with change from baseline Clinical Dementia Rating scale Sum of Boxes (CDR-SB). In the Core study, a correlation in change from baseline in amyloid PET SUVR and plasma Abeta42/40 ratio and plasma P-tau181 was observed at 18 months, indicating that plasma biomarkers could potentially help with measuring clinical changes.

- When lecanemab treatment was discontinued at the end of the Core study, changes in the plasma Abeta42/40 (47%), P-Tau18 (24%), and amyloid PET SUVR (21%), gradually began to reverse, suggesting stopping therapy prematurely may potentially allow re-accumulation of pathology. Less frequent maintenance treatment to prevent re-accumulation may be possible based on data and modeling. Eisai will further explore maintenance dosing in the subcutaneous substudy of the Study 201 OLE, which will evaluate alternative dosing every 4 weeks or every 12 weeks.

- Increasing strong evidence highlights the role of amyloid plaques in triggering tau dysregulation and researchers optimize tau therapeutics by removing a key driver of tau dyshomeostasis (amyloid). For this reason, the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, selected lecanemab as the backbone anti-amyloid therapy for anti-tau combination for the ongoing component of the Tau NexGen clinical study, which continues enrollment efforts.

4. Update on Lecanemab Clinical Development, Including New Subcutaneous Formulation
Eisai's Dr. Michael Irizarry Senior VP of Clinical Research and Deputy Chief Clinical Officer presented updates on key lecanemab clinical trials.

- Clarity AD Phase 3: The innovative Bayesian design of lecanemab's robust dose-ranging Phase 2b study allowed Eisai to design the Phase 3 confirmatory Clarity AD clinical trial to verify lecanemab's clinical efficacy and safety in early AD. Enrollment is complete with 1,795 participants globally. Additionally, Eisai's recruitment strategy for the Clarity AD clinical trial ensured greater inclusion of ethnic and racial populations in the U.S., resulting in approximately 25% of the total U.S. enrollment including Hispanic (22.5%) and African American (4.5%) persons living with early AD, which mirrors the U.S. Medicare population. The readout will occur in Fall 2022.

- AHEAD3-45 Phase 3 Study in Preclinical AD: As of March 2022, there were over 2,900 people screened, resulting in 287 participants enrolled.

- Clarity AD Subcutaneous Substudy: Eisai is developing a subcutaneous formulation of lecanemab with the potential to be administered at home by the patient or caregiver via an auto-injector with a more rapid administration than the IV formulation (<15 second SC injection versus ~1h infusion). PK/PD modeling of Study 201 suggests that the average lecanemab concentration (Cave) predicts amyloid clearance while the maximal lecanemab concentration (Cmax) predicts ARIA-E rate. Since subcutaneous administration results in a blunted Cmax, the SC dose with comparable Cave to 10 mg/kg IV is hypothesized to have similar amyloid reduction with potentially reduced incidence of ARIA-E relative to IV but less than half the ARIA- E rate as IV. Eisai is evaluating the SC formulation in the Clarity AD OLE.

"The invited lecanemab presentations at AD/PD provide new and exciting insights into how the mechanism of action of late-stage anti-amyloid antibodies differ and how that may help simplify the patient journey by offering a less frequent dosing regimen while providing long-term benefit," said Lynn Kramer, M.D., Chief Clinical Officer, Neurology Business Group, Eisai. "Eisai aims to bring these potential innovations to people living with early AD and healthcare providers as quickly as possible as we work to fulfill our human health care mission."

Lecanemab was granted Breakthrough Therapy and Fast Track designations by the U.S. Food and Drug Administration (FDA) in June and December 2021, respectively. Eisai anticipates completing lecanemab's rolling submission of a Biologics License Application for the treatment of early AD to the FDA under the accelerated approval pathway. Eisai expects to complete this rolling submission in the first quarter of our fiscal year 2022, which begins April 1, 2022. Eisai initiated a submission to the Pharmaceuticals and Medical Devices Agency (PMDA) of application data of lecanemab under the prior assessment consultation system in Japan in March 2022. Additionally, the readout of the Phase 3 confirmatory Clarity AD clinical trial will occur in the Fall of 2022. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval.

(1) Swanson C.et all, November, 9-12, 2021, Clinical Trials On Alzheimer's Disease Annual Meeting, Lecanemab: An Assessment of the Clinical Effects, the Correlation of Plasma Abeta 42/40 Ratio With Changes in Brain Amyloid PET SUVr, and Safety from the Core and Open Label Extension of the Phase 2 Proof-of- Concept Study, BAN2401-G000-201, in Subjects With Early Alzheimer's Disease.

Contacts:

MEDIA CONTACT:
Eisai Co., Ltd.
Public Relations Department
+81-(0)3-3817-5120

Eisai Inc. (U.S.) Libby Holman
+ 1-201-753-1945
Libby_Holman@eisai.com

INVESTOR CONTACT:
Eisai Co., Ltd.
Investor Relations Department
+81-(0)70-8688-9685

MEDIA CONTACT:
Biogen Inc. Ashleigh Koss
+ 1-908-205-2572
public.affairs@biogen.com

INVESTOR CONTACT:
Biogen Inc. Mike Hencke
+ 1-781-464-2442
IR@biogen.com

For more information, visit https://www.eisai.com/news/2022/pdf/enews202221pdf.pdf.


Copyright 2022 JCN Newswire. All rights reserved. www.jcnnewswire.comEisai Co., Ltd. and Biogen Inc. announced today that the latest findings on lecanemab, an investigational anti-amyloid-beta (Abeta) protofibril antibody being developed for the treatment of early Alzheimer's disease (AD), were presented at the Abeta Targeted Therapies in AD 2 Symposium at the 2022 International Conference on Alzheimer's and Parkinson's Diseases (AD/PD) March 15-20 in Barcelona, Spain and virtually.

The Eastern Band of Cherokee Indians is facing a labor crisis at its two North Carolina casinos. The Charlotte Observer reports that almost 800 jobs are currently unfilled at its flagship Harrah’s Cherokee Resort, and 90 at its sister property, Harrah’s Cherokee Valley River Casino in Murphy. Tribal council member Boyd Owle said during a […]

The post Eastern Band of Cherokee Facing Major Labor Shortage at North Carolina Casinos appeared first on Casino.org.

A new season of Fortnite means a new population of NPCs to meet and greet--or sometimes defeat. On the island right out of the gate with Chapter 3, Season 2 are 24 NPCs ranging from returning heroes to brand-new ones. Many of them offer unique weapons, perks like storm circle information, and items for sale, so aside from simply filling out your collection, you'll want to meet them all as soon as possible so you can know where to find some of Fortnite's best gameplay items. Here's where to find all Fortnite NPCs in Chapter 3, Season 2.

Fortnite Chapter 3, Season 2 NPC map

There are 24 NPCs on the island currently. While some are just where they were last season, many more are in new places, or have never even been in the game as NPCs until now. As usual, not all NPCs are available in every round. Some groups of NPCs rotate in and out in places like Camp Cuddle and The Joneses, for example. We've made it clear which ones will be trickier to find as a result of variable spawn rates. Use our map below to help locate all NPCs for related challenges, items, and to read their lore-heavy dialogue.

Fortnite Chapter 3 Season 2 NPC locations

1. The Origin - At the northern end of Sanctuary
2. The Imagined - Can be found at one of several Seven Outposts
3. The Visitor - At Launchpad, northeast of Sanctuary
4. The Scientist - In the garage at Synapse Station
5. Agent Jones - Can be found at one of several Seven Outposts
6. The Foundation - Patrolling the south-central region of Sanctuary
7. Bunker Jones - In The Joneses; not present every round
8. Ludwig - In The Joneses; not present every round
9. Brainiac - Walking a dirt path west of The Joneses; not present every round
10. Mullet Marauder - In The Joneses; not present every round
11. Jonesy The First - In The Joneses; not present every round
12. Cuddle Team Leader - In Camp Cuddle, inside the northernmost cabin near the wood bridge
13. Metal Team Leader - In Camp Cuddle, inside the metal cabin; not present every round
14. Cuddlepool - In Camp Cuddle, inside the red cabin; not present every round
15. Quackling - In Camp Cuddle, inside the yellow cabin; not present every round
16. Guaco - In Greasy Grove, hiding in an attic of a yellow house
17. Lil Whip - In Coney Crossroads, hiding in a room in a white house
18. Bao Bros - In Condo Canyon, hiding inside a motel
19. Tomatohead - In Tilted Towers, hiding in a tall building near the soccer field
20. Mancake - In Rocky Reels, hiding below the movie screen
21. Peely - In The Daily Bugle, hiding in the central newspaper office
22. Gunnar - Inside Command Cavern patrolling at ground level; hostile
23. Huntmaster Saber - Inside the Airship flying above Command Cavern; hostile
24. Doctor Slone - The Fortress, patrolling outside the massive drill

The reason so many NPCs are in hiding is that they are a part of the Resistance, the group of loopers who have taken up arms to drive out the Imagined Order. These heroic NPCs have formed makeshift operating stations complete with Seven tech in small, easy-to-miss rooms where the IO hopefully won't find them.

Also note which NPCs are hostile, as they'll shoot you on sight. However, this also means they each drop Mythic weapons, which are unique and can only be equipped by one person at a time, as there are no duplicates. As for the NPCs at The Joneses or Camp Cuddle, remember that they won't all spawn in every round.

At The Joneses, you'll usually be missing one or two versions of Jones in each round, while at Camp Cuddle, just one of the three NPCs in small colorful cabins will spawn in each round--alongside the everpresent Cuddle Team Leader--so you'll need to pass through several times until you meet everyone. Agent Jones and The Imagined, meanwhile, both spawn at any Seven Outpost, though they don't seem to spawn at the same one in the same round, so this look does require a bit of luck.

As more NPCs arrive on the island this season, we'll update our list and map so you can meet them quickly and fill out your collection book once more. For more on Fortnite Chapter 3, Season 2, check out our guide to the new weapons, map changes, and the battle pass.

Russia’s invasion of Ukraine turned out to be a shock to the global community despite the threat that had been growing for months preceding it. Although the military action is taking place within the Ukrainian boundaries, the financial disruption it brought about has spread far beyond. The global stock market is tumbling, the oil and […]

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Over the last week, Chinese stocks have fallen dramatically. Of course, other markets have had substantial drops over-generalized risk-off moves around the war in Ukraine. The drama of the war has overshadowed a lot of financial markets. The situation in China could have been dismissed as another manifestation of the consequences of geopolitics. However, China […]

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It seems today, everyone wants to quit something, and not everyone is having an easy time of it. Whether you’re going to therapy, trying some quick fix being advertised on TV, or depending on will power, it’s hard to change from hard-set patterns. So, it’s always nice to know when a better method might be […]

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Money can’t buy happiness, but affordability of a city sure does have a big impact on wellbeing. With the cost of living rising, here are some of the places where you can live comfortably on a budget.

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Tallin, Estonia, Mar 19, 2022 - (ACN Newswire) - Viblos announces the launch of its decentralized social media project. Viblos is a next-generation decentralized social platform that aims to democratize social media networks in order to help consumers and content providers to build businesses and wealth. Viblos will move this vision forward by completing the following tasks:

• Giving creators control over their own work.
• Encouraging authors to create genuine content.
• Eliminating fake news by providing a content creation and consumption system that's verifiable and transparent.
• Enacting the right to erasure, which allows users to select whether or not their content should remain on

Over the past decade, many prominent social media platforms have progressed from being basic entertainment venues to becoming a cornerstone in many communities' way of life. Today, these websites are owned by a small number of major platforms that have complete control over the internet. While these platforms undoubtedly provide a respectable service to their consumers, the benefits they provide come at an exorbitant price that most users are unaware of. This is primarily due to the fact that the vast majority of users don't actually read through all of the terms and conditions when joining a social media network. In addition to disregarding consumer privacy, the algorithms and political inclination of these platforms are skewed when it comes to ranking content.

Sharing is a fundamental human experience and the rise of social networks has provided new opportunities to do so. Because of the intimate experiences that social networks provide, their membership has exploded in the last ten years. According to DataReportal, there were 4.33 billion active social media users in the world as of 2021. This equates to more than 55 percent of the worldwide population and more than 90 per cent of active internet users. Furthermore, according to recent figures, the average user spent more than two hours and 25 minutes on social media in 2020, which is an increase compared to the two hours and 22 minutes the year before.

At the same time, mobile phones are used by around 67 per cent of the world's population, with smartphones accounting for more than 75 per cent of all mobile devices. Because most mobile phone users access these platforms through their phones, the development of mobile devices has spurred the expansion of social networks. The increasing amount of time spent on these networks has opened up new chances for advertisers and other campaigns, as well as offered useful insights into user behavior. When social networks first began, they relied heavily on advertising and sales to make money.

How Are Blockchain and Decentralization Changing Traditional Social Media?

Here are the five primary hurdles that conventional social media networks must overcome:

• Unequal monetization strategy:According to Social Media Examiner, 3,500 advertising impressions (CPM) equals a measly US$8.75 per month for the content creator Some platforms don't compensate authors at all, or worse, stop monetizing them at all, simply because they express beliefs that are contrary to the platforms' political inclination.
• Privacy concerns:While most networks allow users to select how their information is shared with third parties, this doesn't sufficiently protect the users' privacy. Weak user passwords, which hackers and organizations may readily exploit, exacerbate the situation. According to Pew Research, nearly four out of ten social media users use the same password for multiple accounts.
• Government censorship:In most countries, social networks have essentially turned into public squares, and governments are taking a variety of measures to regulate them. Some administrations have used censorship to achieve their goals. Although users can circumvent prohibitions by using virtual private networks (VPNs), certain countries have cracked down on VPN services, making access to social media information impossible. Without access to social media, users in these nations become alienated as they are unable to communicate with their peers.
• Security:Data leaked from these platforms have recently appeared on the dark web, resulting in an increase in crimes such as credential stuffing. Mainstream social networks collect data directly from users (information about themselves) and indirectly from other users when they post information about their friends. As a result, these networks end up sharing information about members which they themselves would never reveal.

In order to empower and build their enterprises, Viblos also plans to create a common thread and communication channel between celebrities and influencers and their networks. Simply put, we're a go-to platform where your wants and goals, whatever they may be, can come true. Our mantra is "one minute is enough; everything is possible within Viblos".

To find out more about Viblos, visit https://www.viblos.com/.
Twitter: https://twitter.com/Viblos_platform
Telegram: https://t.me/vibloscommunity

Media Contact
Brand: Viblos
Contact: Juan Carlos Pérez Juárez
Email: info@viblos.com
Website: https://www.viblos.com

SOURCE: Viblos

Copyright 2022 ACN Newswire. All rights reserved. www.acnnewswire.com

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Silver Spring, Md. (Monday, March 14, 2022) – Jackson Charitable Foundation, a nonprofit with the mission to advance financial knowledge ... Read more

The Metropolis update for Population: One is available now, with an entire new section of the map and a new game mode to highlight it.