pharmacology

The incidence of and mortality from endometrial cancer (cancer of the uterine lining) have been rising in recent years. When diagnosed at an advanced stage, the prognosis is very poor. A phase 3 clinical trial, coordinated across nearly 30 countries—including Spain—has tested a new treatment for patients whose cancer has progressed following chemotherapy and immunotherapy. The drug combines an antibody designed to target the tumor with a chemotherapy agent that is released once the antibody binds to the tumor cells. The trial, which involved 776 women, showed that the new treatment reduced the risk of cancer progression by 41% and the risk of death by 32% during the study period, compared to standard treatment. The findings are being presented at ESMO, the European Society for Medical Oncology congress currently taking place in Madrid, and are being published simultaneously in The Lancet. 

The administration of intismeran, a personalised therapeutic cancer vaccine developed from each patient’s tumour, together with pembrolizumab immunotherapy following surgery for high-risk melanoma, reduced the risk of recurrence or death by 42 per cent. This phase 3 clinical trial, funded by Moderna and Merck Sharp & Dohme, involved 1,137 patients at very high risk of recurrence who had undergone surgical removal of their melanoma. The companies released preliminary data in August in a press release, and the full results are due to be presented this Saturday at the European Society for Medical Oncology (ESMO) Congress being held in Madrid. Ahead of the announcement, the data were leaked yesterday and the share prices of both companies fell. The scientific paper is due to be published in The New England Journal of Medicine.

Semaglutide is known to reduce the risk of serious heart disease, but a study published in the European Heart Journal suggests that this effect cannot be explained by weight loss alone. The researchers analysed known risk factors for heart disease, such as body weight and waist circumference, in patients taking part in a clinical trial of semaglutide. Although the risk of serious cardiovascular disease was lower among those taking the drug, only half of this reduction could be explained by changes in these risk factors.

Statins are used to prevent atherosclerotic cardiovascular disease (ACD), a specific type of cardiovascular disease caused by the build-up of fatty plaque inside the arteries, which can lead to heart disease or stroke. A study published in The Lancet Healthy Longevity analysed the effect of stopping statins in adults aged 75 and over who were taking them preventatively, that is, without a history of atherosclerotic cardiovascular disease. The results showed that discontinuing treatment was no worse than continuing it in terms of all-cause mortality over a three-year period. According to the authors, these results support individualised decision-making regarding the discontinuation of statin treatment in older people, rather than a blanket recommendation to stop taking them.

A team from the United States exposed pregnant mice to a mild inflammatory agent so that their offspring would develop brain and behavioural changes similar to those seen in autism spectrum disorder. When these offspring reached adulthood, the researchers administered a dose of rapamycin — an immunosuppressant — and found that several of these changes improved for a few hours, including cerebral hyperactivity, the risk of seizures, sensory hypersensitivity, repetitive behaviours and abnormal organisation of the brain’s functional network. The authors, whose work is published in Nature Communications, emphasise in a press release that these effects are temporary and that repeated administration loses its efficacy. Furthermore, they point out that rapamycin’s high potential for toxicity and the fact that the study was conducted on mice rule out its widespread use in humans.

We often see headlines claiming that new research has found a ‘cure’ for diseases. However, what are the real chances of this being true? How does the current stage of the research affect its ultimate outcome? Has it already been tested on humans, or only on laboratory animals? In this article, we explain why animals are used in biomedicine, the reasons why mice are the most commonly used, the steps and timeframes involved from when a treatment appears effective until it can be determined whether it works in people, the characteristics and limitations of various disease models, and how results should be communicated to inform the public without raising false hopes.

In the treatment of obesity, maintaining weight loss is the most difficult phase. Two independent clinical trials published in Nature Medicine have adopted two different strategies to achieve this. The first is a phase 3b trial involving the GLP-1 drug orforglipron, administered orally on a daily basis for 52 weeks. This trial included 376 adults in the United States who had already completed 72 weeks of injectable treatment with tirzepatide or semaglutide. Almost 75% and 80% respectively of patients on each injectable drug maintained their weight loss. The second trial involved 90 obese adults from the Netherlands who followed a low-calorie diet for eight weeks and then received a daily supplement of the bacterium Akkermansia muciniphila for 24 weeks, alongside a healthy diet. Although those who received the supplement regained more than 13% of the weight initially lost, those who took the placebo regained almost 33%.

A review of studies conducted by the Cochrane Collaboration analyzed data from 17 clinical trials involving more than 20,000 participants who had been treated with amyloid-targeting drugs—such as lecanemab or donanemab—at a relatively early stage of Alzheimer’s disease. Results at 18 months of treatment show that “the absolute effects on cognitive decline and the severity of dementia were nonexistent or negligible, falling well below the thresholds established for a clinically meaningful difference,” according to a press release. Furthermore, the review concludes that these drugs likely cause more brain inflammation and microbleeds than the placebo.

A study with Spanish participation has discovered in mice that semaglutide can improve the condition of non-alcoholic fatty liver disease not only through weight loss, but also independently, which would explain why some patients improve with minimal weight loss. “We are not saying that weight loss is unimportant, as many things improve when patients lose weight. But now we know that weight should not be the only measure of success, because GLP-1 drugs will improve liver health regardless of whether the patient loses weight or not,” the authors, who published the results in Cell Metabolism. 

Cancer patients receiving a type of immunotherapy known as Immune Checkpoint Inhibitor (ICI) have a higher risk of serious adverse events, such as aortic aneurysm rupture, interstitial lung disease, myositis and liver failure, according to a study published in PNAS. "Establishing formal contraindications for ICI users seems warranted," concludes the analysis, based on more than 290,000 cases from pharmacovigilance databases of the US Food and Drug Administration and the World Health Organisation.