Cyclerion to Present Trial Design for Phase 2a Study in Alzheimer’s with Vascular Pathology

 Cyclerion Therapeutics, Inc. (Nasdaq: CYCN), a clinical-stage biopharmaceutical company on a mission to develop treatments that restore cognitive function, today announced that it will present clinical trial design for a Phase 2a study of its lead development candidate, CY6463, in participants with Alzheimer’s disease with vascular pathology at the upcoming Alzheimer’s Association International Conference 2021 (AAIC). AAIC will be held July 26-30, 2021, virtually and in Denver, CO.

In addition, Anna Marin, a researcher in the laboratory of Dr. Andrew Budson and Dr. Katherine Turk in the Department of Neurology, Boston University School of Medicine and Center for Translational and Cognitive Neuroscience, VA Boston Healthcare System, will present results from the Cyclerion sponsored study on peak alpha frequency and N200 latency as predictors of neuropsychological performance in a memory disorders clinic. This pioneering work provides insights into the relationships between electrophysiological measures and cognitive performance in patients with Alzheimer’s disease and other dementias. Cyclerion identified changes in electrophysiological measures in the recent Phase 1 Translational Pharmacology study and will be evaluating electrophysiological and cognitive endpoints in the Phase 2a study in participants with Alzheimer’s disease with vascular pathology.

Cyclerion Poster Presentation Details:

Title: Clinical trial design for a Phase 2a study evaluating the safety, tolerability, pharmacokinetics, and CNS activity of CY6463 in participants with Alzheimer’s disease with vascular pathology

Poster Number: P-54463

Presenter: Chad Glasser, Ph.D., Director of Clinical Research, Cyclerion Therapeutics

Authors: Chad Glasser, Jennifer Chickering, Phebe Wilson, Emily Florine, Chris Winrow, Chris Wright

https://finance.yahoo.com/news/cyclerion-therapeutics-present-clinical-trial-203000086.html

Annovis Bio to Present New Data at 2021 Alzheimer's Association

 New efficacy and biomarker data to be featured in panel presentation on Wednesday, July 28. A poster presentation featuring positive clinical outcome data from the Company's two Phase 2a studies will be available on Monday, July 26

Annovis Bio, Inc. (NYSE American: ANVS) ("Annovis" or the "Company"), a clinical-stage drug platform company addressing Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases, with data from two phase 2 studies showing its lead compound improves cognition in AD patients and motor function in PD patients, today announced that it will present new data for its lead product candidate, ANVS401, at the 2021 Alzheimer's Association International Conference (AAIC), which is being held in Denver, Co and virtually, from July 26 through July 30.

On Wednesday, July 28, at 8 p.m. ET, Annovis Bio will host a panel presentation which will include new efficacy and biomarker data from an interim analysis of the Company's ongoing Phase 2a trials. The data presented will include:

• Neurotoxic protein levels

• Marker of axonal damage

• Inflammatory markers

• Efficacy

"We are excited to share our latest data at AAIC as we continue to advance our novel approach to treating Alzheimer's disease," stated Maria L. Maccecchini, Ph.D., CEO of Annovis Bio.

ANVS401 will also be featured in a poster presentation: Positive Clinical Outcomes in Two Phase 2a Studies: ADAS-Cog in Alzheimer's and MDS-UPDRS in Parkinson's patients plus Markers of Toxic Cascade that Leads to Nerve Cell Death.

Previously, Annovis Bio reported that AD patients treated with ANVS401 for 25 days showed a statistically significant 30% cognitive improvement as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11); PD patients treated with ANVS401 showed a statistically significant 18% motor function improvement as measured by the MDS-UPDRS. Additionally, in a test that measures speed and accuracy, AD and PD patients both responded with a statistically significant increase in correctly coded fields. The Company also measured inflammatory factors and found statistically significant lowering of these factors. These tests were part of the Company's ongoing Phase 2a study in AD and PD patients.

https://finance.yahoo.com/news/annovis-bio-present-data-2021-123000434.html

Cortexyme to Present New Data at Alzheimer's Conference

 Cortexyme, Inc. (Nasdaq: CRTX), a company advancing a pivotal trial in Alzheimer’s disease with top-line data expected in the fourth quarter of 2021 and a growing pipeline of therapeutics for degenerative diseases, announced that it will present two poster presentations covering an update from its pivotal Phase 2/3 GAIN Trial of atuzaginstat, in addition to new data demonstrating the upstream role that P. gingivalis plays in key pathology of Alzheimer’s disease, at the Alzheimer's Association International Conference® 2021 (AAIC®) taking place July 26-30, 2021, in Denver, Colorado, as well as virtually.

AAIC 2021 Poster Presentation Details

Topic: An update and baseline data from the Phase 2/3 GAIN trial of COR388 (atuzaginstat), a novel bacterial virulence factor inhibitor for the treatment of Alzheimer’s Disease

• Presenter: Michael Detke, MD, PhD, Cortexyme’s Chief Medical Officer

• Authors: Michael Detke, MD, PhD1, Shirin Kapur, PhD1, Marwan Sabbagh, MD2, Mark Ryder, DMD3, Ira Goodman, MD4, Debasish Raha, PhD1, Florian Ermini, PhD1, Mai Nguyen, PhD1, Ursula Haditsch, PhD1, Joanna Bolger1, Dave Hennings, PhD1, Kim Perry, PhD5, Kelly Ritch, MS6, Casey Lynch1, Hatice Hasturk, DDS, PhD6, Leslie J. Holsinger, PhD1, Stephen Dominy, MD1

Topic: Examining phospho-tau217 in neuron cultures and CVN mice infected with Porphyromonas gingivalis and effects of gingipain inhibition

• Presenter: Florian Ermini, PhD, Cortexyme’s Associate Director, In Vivo Pharmacology and Translational Biology

• Authors1: Florian Ermini, PhD, Ursula Haditsch, PhD, Aurora Martinez-Horta, Leo Rodriguez, Sean Broce, Mai Nguyen, PhD, Debasish Raha, PhD, Shirin Kapur, PhD, Leslie Holsinger, PhD, Casey Lynch, Stephen Dominy, MD

Cortexyme’s posters will be available on Monday, July 26, 2021, beginning at 10:00 a.m. Eastern Time (8:00 a.m. Mountain Time) via AAIC 2021’s virtual conference experience here, as well as on the company’s website under the Science section accessible here.

https://finance.yahoo.com/news/cortexyme-present-data-aaic-2021-120000134.html

Congress to add delay to Part D rebate rule to help pay for infrastructure package

 The Senate aims to delay a controversial rebate rule to help pay for a roughly $1 trillion package, but faces fierce pharma opposition. 

Sen. Joe Manchin, D-W.Va., confirmed on late Thursday to Politico that the package will include a delay to help pay for the package, but did not say for how long. 

The rule would eliminate a safe harbor for Medicare Part D rebates and replace it with a new protection for discounts offered at the point-of-sale. The regulation, which has stiff opposition from the pharmacy benefit management and insurer industries, was delayed by the Biden administration until Jan. 1, 2023. 

The Pharmaceutical Research and Manufacturers Association, a top drug lobbying group, took a preemptive shot earlier this week to avert any delay in the rebate rule.

“Despite railing against high drug costs on the campaign trail, lawmakers are threatening to gut a rule that would provide patients meaningful relief at the pharmacy,” said Debra DeShong, executive vice president of public affairs for PhRMA, in a statement.

DeShong added that including a delay in the infrastructure package will “provide health insurers and drug middlemen a windfall and turn Medicare into a piggy bank to fund projects that have nothing to do with lowering out-of-pocket costs.”

The rebate rule was released under the Trump administration and sought to address Part D drug rebates that drug makers offer to pharmacy benefit managers in exchange for participation on their formularies. Rebates had a safe harbor that provides protection from federal anti-kickback laws. The rule would get rid of this safe harbor and replace it with a new protection for discounts offered at the pharmacy counter.

Former Department of Health and Human Services Secretary Alex Azar touted the rule as a method to get rid of rebates, which he has called a kickback that drug makers are forced to give to PBMs and insurers.

But the rule was withdrawn in 2019 after concerns from the White House that it would raise Part D premiums for seniors. It was later resurrected in late 2020.

PBMs and insurers have fervently fought the regulation, pointing to a report from the Centers for Medicare & Medicaid Services actuaries that the rule would raise premiums by 19%.

While the Biden administration delayed implementation of the rule for another year, PBMs and insurers have asked Congress to fully nix it.

A report from the nonpartisan Congressional Budget Office projected that the rule would increase federal spending by $177 billion through 2029. The increase in spending would come from an increase in premiums and drugmakers implementing a chargeback system where they withhold some of the discounts they previously negotiated with payers, the report said.

The bipartisan infrastructure package includes roughly $1 trillion in spending on projects such as roads and IT infrastructure.

It is being considered separately from a $3.5 trillion package that includes several healthcare priorities such as expanding Medicare benefits to add dental, hearing and vision. Democratic senators also hope to give Medicare the power to negotiate for lower drug prices.

https://www.fiercehealthcare.com/payer/pharma-pushes-back-congress-flirtation-delaying-rebate-rule-to-help-pay-for-infrastructure

Happify Health debuts digital app to tackle both anxiety and depression

 Happify Health has launched a digital therapeutic designed to help diagnose and manage major depressive disorder as well as generalized anxiety disorder, as the two conditions often go hand-in-hand.

Offered as a supplement to standard care, the prescription Ensemble app includes courses for daily skills and coping habits as well as a digital coach named Anna that provides content from psychologists and psychotherapists aimed at the mental processes common to both anxiety and depression.

“The worldwide epidemic of depression and anxiety rages on, affecting 1 in 5 people—but between 30-40% of those needing treatment for these disorders do not receive it for one reason or another,” Happify’s chief science officer, Acacia Parks, said in a statement.

Ensemble was also born out of another epidemic—the worldwide spread of COVID-19. During the early stages of the pandemic in April 2020, the FDA announced a policy to expand the use of low-risk digital tools for psychiatric disorders, to help reduce patient-and-provider contact amid lockdowns and social distancing measures. 

Happify’s investigational app, which relies on a 10-week cognitive behavioral therapy program, is currently being offered under this agency policy, and users may be able to enroll in the company’s virtual research study to help test its safety and efficacy. The app has not been cleared by the FDA.

“With mental health disorders exploding as a result of the pandemic, significant shortages of mental health clinicians, high costs of treating mental health disorders and a high degree of variability in applying cognitive behavioral therapy, mindfulness and positive psychology to treat these patients, clinicians need an evidence-based therapy like Ensemble to treat their patients,” said Happify digital therapeutics head Chris Wasden. 

At the same time, people with a major depressive disorder are over five times more likely to have generalized anxiety disorder, compared to those without, Wasden said, and that about 20% of people diagnosed with depression also meet the criteria for anxiety over the course of a year.

The app includes a dashboard for physicians to help monitor their patients’ progress while tracking improvements using clinically validated questionnaires. Happify has previously used its digital platform in collaboration with pharma companies to help treat mental health issues that may come along with chronic medical conditions—such as with the Spanish drugmaker Almirall in patients with severe psoriasis and with Sanofi in multiple sclerosis.

This past March, Happify raised $73 million to help expand its digital reach and pharma partnerships. The company’s series D round was backed by Deerfield Management, Omega Capital Partners, ION Crossover Partners and other previous investors.

https://www.fiercebiotech.com/medtech/happify-health-debuts-digital-app-to-tackle-both-anxiety-and-depression

COVID-19 hospital admissions: Brazil's first and second waves compared

 

• Leonardo SL Bastos
• Otavio T Ranzani
• Thiago Moreno L Souza
• Silvio Hamacher
• Fernando A Bozza

DOI: https://doi.org/10.1016/S2213-2600(21)00287-3

PDF: https://www.thelancet.com/action/showPdf?pii=S2213-2600%2821%2900287-3

Brazil is one of the countries most affected by the COVID-19 pandemic, with more than 16 million confirmed cases and 454 429 confirmed deaths by May 26, 2021 (according to the Johns Hopkins Coronavirus Resource Center). The beginning of 2021 was marked by a second wave of COVID-19, which had different features to the first wave,

1

 with simultaneous, explosive surges of COVID-19 cases across different regions of the country that added enormous pressure to a health system already under strain after a year of the pandemic. This second wave was contemporary with the discovery, expansion, and dominance of variants of interest (VoI) and variants of concern (VoC) in Brazil.

2

We previously characterised the first 250 000 hospital admissions for COVID-19 in Brazil, including resource use and in-hospital mortality of patients.

1

 We now compare the burden, severity (number of patients with hypoxaemia), resource use (intensive care unit admission and respiratory support), and in-hospital mortality of COVID-19 hospitalised patients between the first and second waves. From the Brazilian nationwide surveillance database for severe acute respiratory infections, SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe), we extracted 1 217 332 COVID-19 hospital admissions from Feb 16, 2020, to May 24, 2021 (ie, epidemiological week 8, 2020, to epidemiological week 21, 2021). For the quantitative comparison between waves, we extracted data available until May 24, 2021, and excluded the previous four epidemiological weeks to account for a potential delay in notifications appearing on the database, resulting in 1 187 840 hospital admissions (for a link to data sources and additional analyses, see appendix p 1; national and regional comparisons will be updated regularly on the SIVEP COVID-19 Brazil app).

• View related content for this article

The hospital admission dynamic showed a second surge after epidemiological week 43 in 2020, defined by the lowest value per week of hospitalised cases (figure). Comparing the first wave with the second wave (ie, comparing the period of weeks 8 to 43 in 2020 vs the period from week 44 in 2020 to week 21 in 2021), average figures per week had increased for admissions by 59% (14 220 vs 22 703; appendix p 1), for patients with hypoxaemia by 72% (8606 vs 14 845), for non-invasive ventilation by 74% (6746 vs 11 773), and for invasive mechanical ventilation by 53% (2452 vs 3747). Remarkably, the maximum number of admitted patients per week requiring advanced respiratory support (ie, non-invasive ventilation, or invasive mechanical ventilation, or both) was 13 985 (week 28 in 2020) in the first wave, which increased by 192% to 40 797 (week 10 in 2021) in the second wave. Although more patients with hypoxaemia received respiratory support in the second wave than in the first wave, there was no increase in the proportion of patients admitted to the intensive care unit (37·6% vs 37·5%), which suggests a potential limitation in access to critical care (appendix p 1). Interestingly, there were fewer admissions from state capitals in the second wave than in the first wave (48·2% vs 37·5%).

FigureTemporal increases in COVID-19 hospital admissions and deaths in Brazil, stratified by severity (hypoxaemia), age, and respiratory support

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During the second wave, on May 26, 2021, in epidemiological week 53, Outbreak.info reported that the E484K mutation among SARS-CoV-2 variants in Brazil was present in more than 50% of viral genomes,

3

 motivating specific comparisons of admissions before and after dominance of VoI or VoC. The median age of patients decreased (63 years vs 59 years), with a relative increase of 18% in the proportion of patients younger than 60 years. The in-hospital mortality increased from 33·1% to 40·6% in the general population, and also in patients who received respiratory support (24·8% vs 28·6% non-invasive ventilation, 78·8% vs 84·1% invasive mechanical ventilation). However, the proportion of deaths should be interpreted with caution because of a substantial number of ongoing admissions (appendix p 1).

Based on the available data of 1 217 332 COVID-19 adult hospitalisations in Brazil, the second wave's progression resulted in an increased burden of severe cases similar to the situation seen in the UK

4

 and Africa.

5

 The Brazilian health-care system was overwhelmed during the first wave, and now indicates resource constraints, or even collapse, in a scenario of low adherence to non-pharmacological interventions and convergent dominance of the VoC. However, our research cannot establish a causal relationship between VoC lineages and higher burden of severe cases or increased pathogenicity of the virus. These findings indicate the need for urgent action to contain transmission, expand vaccination coverage, and improve critical care for COVID-19, by providing access to health services and disseminating better available evidence.

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00287-3/fulltext

Cognitive deficits in people who have recovered from COVID-19

 

• Adam Hampshire
• William Trender
• Samuel R Chamberlain
• Amy E. Jolly
• Jon E. Grant
• Fiona Patrick
• et al.
• Show all authors

DOI:https://doi.org/10.1016/j.eclinm.2021.101044

PDF: https://www.thelancet.com/action/showPdf?pii=S2589-5370%2821%2900324-2

Abstract

Background

There is growing concern about possible cognitive consequences of COVID-19, with reports of ‘Long COVID’ symptoms persisting into the chronic phase and case studies revealing neurological problems in severely affected patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of disease severity.

Methods

We sought to confirm whether there was an association between cross-sectional cognitive performance data from 81,337 participants who between January and December 2020 undertook a clinically validated web-optimized assessment as part of the Great British Intelligence Test, and questionnaire items capturing self-report of suspected and confirmed COVID-19 infection and respiratory symptoms.

Findings

People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection (N = 326). Analysing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition.

Interpretation

Interpretation. These results accord with reports of ‘Long Covid’ cognitive symptoms that persist into the early-chronic phase. They should act as a clarion call for further research with longitudinal and neuroimaging cohorts to plot recovery trajectories and identify the biological basis of cognitive deficits in SARS-COV-2 survivors.

Funding

Funding. AH is supported by the UK Dementia Research Institute Care Research and Technology Centre and Biomedical Research Centre at Imperial College London. WT is supported by the EPSRC Centre for Doctoral Training in Neurotechnology. SRC is funded by a Wellcome Trust Clinical Fellowship 110,049/Z/15/Z. JMB is supported by Medical Research Council (MR/N013700/1). MAM, SCRW and PJH are, in part, supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00324-2/fulltext