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Xtandi drug combo cuts risk of death by 58% in prostate cancer patients

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A new drug combo has been shown to boost metastasis-free survival by 58% in prostate cancer patients at high risk of biochemical recurrence.

Astellas Pharma and Pfizer say the drug Xtandi combined with an androgen deprivation therapy has the potential to be the new standard of care in patients with high risk biochemical recurrence (BCR) if a label expansion is approved.

The two companies have reported full data at the American Urological Association Annual Meeting from a late stage phase 3 trial, dubbed Embark.

In the trial Astellas and Pfizer tested out Xtandi plus leuprolide against a placebo plus leuprolide in 1,068 men with non-metastatic hormone-sensitive prostate cancer with a high-risk of BCR.

The Xtandi-leuprolide blend reduced the risk of metastasis or death by 58% versus the placebo plus leuprolide in the multi-national trial conducted at sites in the United StatesCanadaEuropeSouth America and the Asia- Pacific region.

The trial evaluated patients in three study groups – Xtandi plus leuprolide, placebo plus leuprolide, and Xtandi monotherapy – in men with non-metastatic hormone-sensitive prostate cancer with high-risk BCR.

The main aim of Embark was to assess metastasis-free survival (MFS).

Astellas and Pfizer reported that secondary endpoints saw improvements.

In the Xtandi monotherapy group, the drug reduced the risk of metastasis or death by 37%, compared to leuprolide plus placebo.

The combo arm of the trial reduced the risk of prostate-specific antigen progression (PSA-P) by 93% while the monotherapy lowered it by 67%.

The progression risk in starting a new antineoplastic therapy was reduced by 64% in those on Xtandi plus leuprolide and 46% in those on Xtandi monotherapy, versus the leuprolide placebo combo.

The most common adverse effects in the combo arm of the study were fatigue, hot flush and arthralgia (painful or stiff joints). In the patients on the Xtandi monotherapy, the most frequent unfavourable reactions were fatigue, gynecomastia (an overdevelopment or enlargement of the breast tissue in men), and arthralgia.

Detailed results from the trial will now be submitted for peer-reviewed publication. Additionally, the Embark data will be discussed with regulatory authorities, including the US Food and Drug Administration (FDA), to expand the use of Xtandi into a fourth cancer indication.

Xtandi – which is also known as enzalutamide – has been approved for use as a daily therapy in the United States since 2019 in men with metastatic hormone-sensitive prostate cancer, metastatic castration-resistant prostate cancer and non-metastatic castration-resistant prostate cancer.

It was approved for use by the European Commission in May 2021.

Leuprolide – also known as Eligard and Lupron – is an already-approved drug commonly used to treat symptoms of advanced prostate cancer. It works by lowering testosterone levels, which can help slow the growth of cancer cells.

In a statement, Neal Shore, primary investigator for Embark and US chief medical officer of Urology and Surgical Oncology, said the study showed that the drug combo was “statistically significant” for high-risk BCR patients.

He said: “There are patients with localized prostate cancer who undergo prostatectomy or radiation therapy in an attempt to cure their disease, but, unfortunately, some patients will develop BCR.

“Importantly, some patients with BCR are at very high risk for developing metastatic disease, which can lead to a cascade of therapeutic interventions. The clinical goal of BCR therapy is to delay cancer progression and avoid metastatic disease.

“The MFS results from the Embark study demonstrate that this intervention with Xtandi plus leuprolide was statistically significant for patients with high-risk BCR.”

Stephen Freedland, director for the Center for Integrated Research in Cancer and Lifestyle and co=principal investigator of the clinical trial, added: “The Embark study is a Phase 3 trial exploring the potential of enzalutamide in patients with non-metastatic hormone-sensitive prostate cancer with high-risk BCR.

“If approved, we hope to bring a new option to men earlier in the course of their disease.”

Prostate cancer is the second most diagnosed in men globally and the fifth leading cause of death. An estimated 1.4 million new cases of the disease and more than 375,000 deaths are reported every year.

The countries with the highest prostate cancer rates according to statistics compiled by the World Cancer Research Fund International are French Guadeloupe, French Martinique, Ireland, Barbados and Saint Lucia.

There is strong evidence that being overweight and obese and being tall increase the risk of developing prostate cancer. Research suggests that diets high in calcium and high consumption of dairy products might also increase the risk.

Current treatment depends on how big the cancer is, if it has spread, and general health. But the most common are surgery, chemotherapy, radiotherapy and hormone – or androgen suppression – therapy.

 

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Mole rat gene extends mouse lifespan

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A mole rat gene inserted into mice extended lifespan and improved health, findings that may point to new ways of supporting healthier ageing.

The gene increased production of a large form of hyaluronan, a naturally occurring gel-like substance between cells that helps tissue repair and cell-to-cell communication.

Mice carrying the naked mole rat version of the gene showed an approximately 4.4 per cent increase in median lifespan, alongside multiple markers of healthier ageing.

Naked mole rats have become a focus of ageing research because they combine an exceptional lifespan with unusual resistance to many age-linked diseases, including cancer.

Researchers at the University of Rochester traced part of that resilience to hyaluronan.

The molecule’s effects depend on its size: large forms are often linked to anti-inflammatory and tissue-protective behaviour, while smaller fragments can act as danger signals that increase inflammation.

Vera Gorbunova, professor of biology and medicine at the University of Rochester in the US, said: “Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals.”

The engineered mice were better protected against both spontaneous tumours and chemically induced skin cancer.

They also showed reduced inflammation across tissues, a notable finding because persistent low-grade inflammation, sometimes called inflammaging, is widely seen as one of the central drivers of age-related decline.

The research also linked the large form of hyaluronan to age-related gut health. As animals age, the gut barrier can become leakier, allowing inflammatory triggers to pass into the bloodstream.

The engineered mice showed protection against this deterioration.

Follow-up work found abundant high-molecular-mass hyaluronan across multiple species of subterranean mammals, often absent in closely related above-ground species, suggesting it may be part of a broader evolutionary toolkit for surviving long lives under harsh conditions.

The team said gene transfer is not the end goal. Gorbunova said: “It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice.”

“Our next goal is to transfer this benefit to humans.”

Two practical routes are being pursued: increasing production of the large form of hyaluronan, or slowing its breakdown.

Andrei Seluanov, who co-leads the research, said: “We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials.”

One candidate identified through screening is delphinidin, a plant pigment found in various fruits and vegetables.

In tests, it was found to increase levels of the large form of hyaluronan in cells and mouse tissues, reduce migration and invasion in multiple cancer cell lines, and suppress melanoma metastasis in mice.

However, the researchers acknowledged the approach has limits. A later study found that mice expressing the naked mole rat gene showed improvements in several late-life health measures but did not show protection from age-related hearing loss, suggesting some organs may be less reachable by this pathway than others.

The Rochester team said turning these findings into human therapies will likely depend on precision: maintaining the right molecular form of hyaluronan, targeting the right balance of production versus breakdown, and monitoring carefully for trade-offs as different tissues respond in different ways.

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AI can predict Alzheimer’s with almost 93% accuracy, researchers say

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Alzheimer’s AI can predict the disease with nearly 93 per cent accuracy using more than 800 brain scans, researchers say.

The system identified anatomical changes in the brain linked to the onset of the most common form of dementia, a condition that gradually damages memory and thinking.

The findings build on years of research suggesting AI could help spot early Alzheimer’s risk, predict disease and identify patients whose condition has not yet been diagnosed.

Benjamin Nephew, an assistant research professor at the Worcester Polytechnic Institute in Massachusetts, said: “Early diagnosis of Alzheimer’s disease can be difficult because symptoms can be mistaken for normal ageing.

“We found that machine-learning technologies, however, can analyse large amounts of data from scans to identify subtle changes and accurately predict Alzheimer’s disease and related cognitive states.”

The study used MRI scans, a type of detailed brain imaging, from 344 people aged 69 to 84.

The dataset included 281 scans showing normal mental function, 332 with mild cognitive impairment, an early stage of memory and thinking decline, and 202 with Alzheimer’s.

The scans covered 95 of the brain’s nearly 200 distinct regions and used an AI algorithm to predict patients’ health.

Being able to use AI to help diagnose Alzheimer’s earlier could give patients and doctors crucial time to prepare and potentially slow the progression of the disease.

The analysis showed that one of the top predictive factors was brain volume loss, or shrinkage, in the hippocampus, which helps form memories, the amygdala, which processes fear, and the entorhinal cortex, which helps provide a sense of time.

This pattern held across age and sex, with both men and women aged 69 to 76 showing volume loss in the right part of the hippocampus, suggesting it may be an important area for early diagnosis, the researchers noted.

However, the research also found that the way brain regions shrink differs by sex.

In females, volume loss occurred in the brain’s left middle temporal cortex, which is involved in language and visual perception. In males, it was mainly seen in the right entorhinal cortex

The researchers believe this could be linked to changes in sex hormones, including the loss of oestrogen in women and testosterone in men.

These conclusions could help improve methods of diagnosis and treatment going forward, Nephew said.

More than 7.2m Americans are living with Alzheimer’s, according to the Alzheimer’s Association.

More research is being done to reveal other impacting factors.

Nephew said: “The critical challenge in this research is to build a generalisable machine-learning model that captures the difference between healthy brains and brains from people with mild cognitive impairment or Alzheimer’s disease.”

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Vision implant firm raises US$230m

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A vision implant firm has raised US$230m as it seeks approval in Europe and the US for a device that restored sight in a small clinical trial.

The Alameda, California-based startup said the funding would support commercialisation of its Prima device.

It said an upcoming launch is planned in Europe and that it would become the first brain computer interface company to have a vision restoration device on the market.

A clinical trial in Europe found the small implant could work as artificial photoreceptors in the retina to restore functional central vision.

The implant is placed under the retina to replace the function of light-sensitive cells lost to disease. A special pair of glasses with an embedded camera and infrared projector sends light signals to the implant.

The study assessed the system in people with advanced dry age-related macular degeneration.

Of the 38 patients who received an implant, 32 were assessed at 12 months. Results showed the device led to a clinically meaningful improvement in visual acuity in 26 people.

The patients were able to read letters, numbers and words, according to the company.

Science Corporation said it has submitted a CE mark application to the European Union and applied to the US Food and Drug Administration for regulatory approval.

Darius Shahida, chief strategy officer, said: “Our imperative is to become the first BCI company to scale and achieve profitability.”

Founded in 2021, the company has now raised about US$490m in total. It said it is expanding its clinical trial programme to include other retinal diseases, such as Stargardt disease and retinitis pigmentosa.

The Series C round included existing investors Khosla Ventures, Lightspeed Venture Partners, Y Combinator, IQT and Quiet Capital.

Science Corporation said demand for the round exceeded its capital needs, with funds also earmarked for expanding research, manufacturing infrastructure and operations.

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