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pharmaphorumuk · 5 years

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Last BACE bombs: Eisai, Biogen give up on elenbecestat

The final BACE inhibitor in clinical testing for Alzheimer’s disease – Eisai and Biogen’s elenbecestat – has been abandoned.

The two companies have decided to discontinue their remaining two phase 3 trials of elenbecestat in patients with early-stage Alzheimer’s after a review of the drug’s safety revealed an “unfavourable risk-benefit ratio.”

Elenbecestat joins an ever-lengthening list of Alzheimer’s drugs that have fallen at the last hurdle in clinical testing, including several BACE inhibitors, and further undermines any hope that the progression of the dementia-causing disease can be held up by drugs that target amyloid.

BACE inhibitors reduce the production of amyloid beta in the brain by blocking an enzyme (beta secretase) involved in the formation of the amyloid peptides that clump together to form the characteristic plaques seen in Alzheimer’s-affected brains.

Interest in BACE gathered pace after antibody drugs designed to destroy already-formed plaques failed, on the premise that interrupting their formation might be more effective.

It has proved a fruitless endeavour however as elenbecestat joins BACE drugs from Novartis/Amgen, AstraZeneca/Eli Lilly, Merck & Co/MSD, and Roche, either because of a lack of efficacy or side effects.

It’s not the end for elenbecestat, as the academic-led Alzheimer’s Clinical Trials Consortium (ACTC) has confirmed that it will still press ahead with two trials of the drug announced earlier this year, despite Eisai and Biogen’s decision.

Due to start enrolling next year, the A3 and A45 trials are being backed by a public-private partnership set up between Eisai, the US National Institutes of Health and philanthropic organisations.

The A3 trial will recruit people without any cognitive impairment or amyloid elevation, but are at risk of amyloid accumulation, following the trend of trying to intervene ever-earlier in the course of Alzheimer’s.

A45 will target pre-symptomatic or ‘prodromal’ Alzheimer’s, in other words enrolling subjects with elevated amyloid but no cognitive impairment. Elenbecestat will be tested as a maintenance therapy after BAN2401, another Eisai/Biogen Alzheimer’s drug that can be used to clear amyloid deposits from the brain.

BA2401 also failed to show any improvement at 12 months in a phase 2 trial, although the study has been extended to see if longer-term treatment (up to five years) can show an effect on cognition.

Earlier this year Eisai and Biogen started a phase 3 trial of the drug – called CLARITY AD – in early symptomatic Alzheimer’s, that is due to complete in 2024.

The demise of elenbecestat comes shortly after Biogen was forced to abandon another amyloid-targeting Alzheimer’s candidate – aducanumab – and its pledge to keep plugging away at the disease despite shareholder concerns.

Along with BAN2401 the company is also looking at drugs to block the formation of tau protein tangles that also characterise the disease, although that approach has also failed to show any benefit in the clinic to date.

Meanwhile, Alzheimer’s researchers are starting to shed their fixation on amyloid and are looking at other factors in the disease, including inflammation, oxidative stress and other protein targets like alpha-synuclein and RIPK1.

The post Last BACE bombs: Eisai, Biogen give up on elenbecestat appeared first on Pharmaphorum.

from Pharmaphorum https://pharmaphorum.com/news/last-bace-bombs-eisai-biogen-give-up-on-elenbecestat/

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serinakemp · 7 years

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Fight Aging! Newsletter, September 25th 2017

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Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more.

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Contents

HSP90 Inhibitors as Another New Class of Potential Senolytic Drug Compounds

An Introduction to DAF-16 and FOXO in the Context of Aging and Longevity

Evidence Accumulates for Macrophages to be Central to Exceptional Regeneration

MicroRNA in Macrophage Exosomes Mediates Harms Done by Visceral Fat Tissue

Wolf has been Cried So Very Many Times When it Comes to Anti-Aging Therapies

The First Practical Means of Human Rejuvenation are Not Distant

Reviewing the Effects of Exercise on Mitophagy and Mitochondrial Function

Is Dementia Incidence in Decline?

Aiming to Develop Monoclonal Antibodies for Glucosepane

Encapsulated Stem Cells Improve Heart Regeneration

RIPK1 as a Target to Reduce Microglial Dysfunction in Alzheimer's Disease

Frailty is Not Entirely Irreversible, Even Now

Adjusting Neutrophil Behavior to Enhance Stroke Recovery

Even Lower Levels of Activity are Associated with Improved Health

Alternative Splicing and Cancer

HSP90 Inhibitors as Another New Class of Potential Senolytic Drug Compounds http://ift.tt/2xMoki3

The increasing number of senescent cells present in older tissues is one of the root causes of degenerative aging. It is also the closest to being effectively reversed. An open access paper describing the evidence for HSP90 inibitors to selectively destroy senescent cells was published earlier this month. I...