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New combination therapy shows promising results for prostate cancer

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A novel combination prostate cancer therapy has been approved by the US Food and Drug Administration.

The new treatment combines two Pfizer-produced cancer drugs, Xtandi (also known as enzalutamide) and Talzenna (which also goes under the name talazoparib).

While Xtandi is a medication typically used for prostate cancer, the addition of Talzenna – an oral poly ADP-ribose polymerase (PARP) inhibitor – is new in patients with the disease.

The FDA approval specifically applies to adults with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

This type of cancer has spread beyond the prostate gland and progressed despite surgery and other treatment to lower testosterone.

Approximately 10%-20% of patients with prostate cancer develop mCRPC within five to seven years of diagnosis. HRR gene mutations are found in approximately 25% of tumours from men with mCRPC and have been associated with aggressive disease and poor prognosis.

In a phase 3 TALAPRO-2 trial, this drug combination was found to decrease the risk of cancer progression by 55%, compared to the standard treatment in these patients for whom the FDA approved the combination.

Neeraj Agarwal. Image: Huntsman Cancer Institute

Neeraj Agarwal, Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute at the University of Utah and global lead investigator for TALAPRO-2, said: “Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy.

“Therefore, new first-line treatment options are needed to reduce the risk of disease progression or death. For patients with mCRPC harbouring HRR genetic alterations, outcomes are even worse.

“The FDA’s approval of the talazoparib and enzalutamide combination is based on the findings from the pivotal TALAPRO-2 study, which demonstrated statistically significant and clinically meaningful reductions in the risk of progression or death among HRR gene-mutated tumours in patients with metastatic castration-resistant prostate cancer.

“It represents a treatment option deserving of excitement and attention.”

The approval came just days after he published the findings of the study in The Lancet, as the lead author, a first in institutional history.

The Phase 3 TALAPRO-2 trial is a two-part, two-cohort, multicentre, randomised, double-blind, placebo-controlled study that included two patient cohorts.

The safety of Talzenna and Xtandi in the TALAPRO-2 trial was generally consistent with the known safety profile of each medicine. Serious adverse reactions occurred in 30% of patients treated with Talzenna plus Xtandi. Serious adverse reactions reported in more than 2% of patients included anaemia (9%) and fracture (3%). Discontinuation of Talzenna occurred in 10% of patients.

A marketing authorisation application (MAA) for the Talzenna and Xtandi combination has been accepted for review by the European Medicines Agency. Pfizer has also shared data with other regulatory agencies to support regulatory filings.

Angela Hwang, chief commercial officer, president, global biopharmaceuticals business, Pfizer, said: “Pfizer has a legacy of bringing medicines to patients with genitourinary cancers and helping improve outcomes for patients suffering from advanced prostate cancer.

“As a global standard of care, Xtandi has shown efficacy in three types of prostate cancer, and the addition of Talzenna demonstrated significant improvements in delaying or preventing radiographic progression-free survival or death in patients with this type of advanced prostate cancer.”

She added that with the FDA’s approval of Talzenna plus Xtandi “we are proud to be able to offer this potentially practice-changing treatment to patients and add to their options in managing this aggressive disease.”

Prostate cancer is one of the most common types. Around one in eight men will be diagnosed with it in their lifetime.

According to the American Cancer Society, about six cases in 10 are diagnosed in men who are 65 or older, and it is rare in men under 40.

Neli Ulrich, chief scientific officer and executive director of the Comprehensive Cancer Center at Huntsman Cancer Institute, said: “This work, led by Dr Agarwal, with colleagues across the world, is absolutely ground-breaking. It will make a big difference in treatment options for many prostate cancer patients.”

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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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