Day: December 2, 2024

Categories : HIVTags :

Trial Shows Twice-yearly Injection to be 99% Effective in HIV Prevention

On By ModernMedia
Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/

For oral medications that prevent new HIV infection to be effective, the patient must take certain actions, including attending doctor’s visits every three months and – most importantly – consistency.

These daily oral antiretrovirals, more commonly referred to as PrEP (pre-exposure prophylaxis), such as Truvada®, are extremely effective at HIV prevention, but only if they are taken daily as directed. Truvada’s efficacy is greatly compromised when taken inconsistently.

However, results from a recent Gilead-funded clinical trial (Purpose-2) led by physicians at Emory University and Grady Health System indicate that a twice-yearly injection of Lenacapavir offers a 96% reduced risk of infection overall, making the injection significantly more effective than the daily oral PrEP. The findings were recently published in the New England Journal of Medicine.

“Seeing these high levels of efficacy – at almost 100% – in an injectable that people only have to take every six months is incredible,” says Colleen Kelley, MD, lead author of the study and professor in the School of Medicine at Emory University. “This is a considerable and profound advancement in medicine, especially for people whose circumstances don’t allow them to take a daily oral medication, and for those among populations disproportionately impacted by HIV.”  

In the randomised, double-blind, Phase III clinical trial comparing the efficacy of the two medications, 99% of the participants in the Lenacapavir group did not acquire an HIV infection. During the trial, only two participants in the Lenacapavir group, comprised of 2,179 people, acquired HIV. This compares to nine new HIV infections in the Truvada®group, which had 1,086 people. The trial showed that adherence to the injectable was higher than of the daily oral pill. 

Kelley adds that while PrEP is incredibly effective at preventing infection, part of what made the injection more effective in the clinical trial was the challenges associated with adherence to a daily oral pill.

“What we see over time is that about half of people who start taking daily oral PrEP stop within a year due to various factors,” says Kelley, referencing healthcare disparities in general. “Having an effective injectable that is only needed twice annually is very significant for people who have trouble accessing healthcare or staying adherent to daily, oral pills.”

The inclusion of racially, ethnically, and gender-diverse participants in the clinical trial was notable because it was representative of populations disproportionately impacted by HIV in real time. For example, the trial groups were comprised of cisgender men and gender-diverse people at 88 sites in Peru, Brazil, Argentina, Mexico, South Africa, Thailand, and the US.

According to the study, the same populations that are disproportionately impacted by HIV are the same populations that have limited access to PrEP – or may have difficulty consistently taking the oral antiretroviral medication – ultimately highlighting the need for more options. The study also indicates that more than half of the new HIV infections nationwide in 2022 were among cisgender gay men, and 70% of those were among Black or Hispanic individuals. 

Valeria Cantos, MD, associate professor in the School of Medicine at Emory University, physician at Grady Memorial Hospital, and the principal investigator for the clinical trial at the Grady research site, emphasized the importance of having trials that include populations truly representative of the patients that Grady serves.

“At Grady, our focus is on increased representation of underserved and vulnerable populations, acknowledging and addressing the distrust towards research held by some community members due to prior abuses or neglect of these populations by research institutions in the past,” Cantos says. “Grady is an established, trusted research site because of its commitment to equity.”

 At the Grady clinical trial site, medical materials were available in Spanish, and bilingual staff members recruited and enrolled trial participants who only spoke Spanish. Cantos also indicated that the site enrolled participants who are representative of the populations that would benefit the most from Lenacapavir. In addition to Grady, the Hope Clinic and Emory Midtown Hospital were among the 88 sites supporting the clinical trial. 

“We are not reaching everyone we need to reach with our current HIV prevention interventions, such as those who are disproportionately impacted by HIV and health care disparities,” says Kelley. “For people that are unable to take the daily oral pills, the injectable agents can really give incredible efficacy and be a game changer in helping them stay HIV negative.”

Since the Phase III clinical trial has been completed and submitted by the FDA for consideration, Kelley is hopeful that Lenacapavir may be approved by 2025 for commercial use.

Source: Emory Health Sciences

Categories : Respiratory DiseasesTags :

First New Treatment for Asthma Attacks in 50 Years

On By ModernMedia
Photo by Louis Reed on Unsplash

An injection given during some asthma and COPD attacks was shown to be more effective than the current treatment of steroid tablets, reducing the need for further treatment by 30%. The findings, published in The Lancet Respiratory Medicine, could be “game-changing” for millions of people with asthma and COPD around the world, scientists say.

The type of symptom flare-up the injection treats are called ‘eosinophilic exacerbations’ and involve symptoms such as wheezing, coughing and chest tightness due to inflammation resulting from high amounts of eosinophils, a type of white blood cell. Eosinophilic exacerbations make up to 30% of COPD flare-ups and almost 50% of asthma attacks. They can become more frequent as the disease progresses, leading to irreversible lung damage in some cases.

Treatment at the point of an exacerbation for this type of asthma has barely changed for over fifty years, with steroid drugs being the mainstay of medication. Steroids such as prednisolone can reduce inflammation in the lungs but have severe side-effects such as diabetes and osteoporosis. Furthermore, many patients ‘fail’ treatment and need repeated courses of steroids, re-hospitalisation or die within 90 days.

Results from the phase two clinical trial ABRA study, led by scientists from King’s College London and sponsored by the University of Oxford, show a drug already available can be re-purposed in emergency settings to reduce the need for further treatment and hospitalisations. The multi-centre trial was conducted at Oxford University Hospitals NHS Foundation Trust and Guy’s and St Thomas’ NHS Foundation Trust.

Benralizamab is a monoclonal antibody which targets eosinophils to reduce lung inflammation. It is currently used for the treatment of severe asthma. The ABRA trial has found a single dose can be more effective when injected at the point of exacerbation compared to steroid tablets.

The study investigators randomised people at high risk of an asthma or COPD attack into three groups, one receiving benralizumab injection and dummy tablets, one receiving standard of care (prednisolone 30mg daily for five days) and dummy injection and the third group receiving both benralizumab injection and standard of care. As a double-blind, double-dummy, active-comparator placebo-controlled trial, neither the people in the study, or the study investigators knew which study arm or treatment they were given.

After 28 days, respiratory symptoms of cough, wheeze, breathlessness and sputum were found to be better with benralizumab. After 90 days, there were four times fewer people in the benralizumab group that failed treatment compared to standard of care with prednisolone.

Treatment with the benralizumab injection took longer to fail, meaning fewer episodes to see a doctor or go to hospital. Quality of life also improved for people with asthma and COPD.

This could be a game-changer for people with asthma and COPD. Treatment for asthma and COPD exacerbations have not changed in fifty years despite causing 3.8 million deaths worldwide a year combined.

– Lead investigator of the trial Professor Mona Bafadhel from King’s Centre for Lung Health

She added: “Benralizumab is a safe and effective drug already used to manage severe asthma. We’ve used the drug in a different way – at the point of an exacerbation – to show that it’s more effective than steroid tablets which is the only treatment currently available. The big advance in the ABRA study is the finding that targeted therapy works in asthma and COPD attacks. Instead of giving everyone the same treatment, we found targeting the highest risk patients with very targeted treatment, with the right level of inflammation was much better than guessing what treatment they needed.”

The benralizumab injection was administered by healthcare professionals in the study but can be potentially administered in the GP practice or in the Emergency Department. Benralizumab was safe in the study and similar in safety to many past studies.

Professor Mona Bafadhel said, “We hope these pivotal studies will change how asthma and COPD exacerbations are treated for the future, ultimately improving the health for over a billion people living with asthma and COPD across the world.”

Source: King’s College London

Categories : Metabolic Disorders UrogenitalTags :

GLP-1 Receptor Agonists also Protect the Kidneys, Study Shows

On By ModernMedia

GLP-1 agonists significantly reduced kidney deterioration and failure, regardless of diabetes status

Chronic kidney disease (CKD). Credit: Scientific Animations CC4.0

The biggest and most comprehensive analysis of glucagon-like peptide-1 (GLP-1) receptor agonists on kidney and cardiovascular outcomes shows they have significant benefits in people with and without diabetes.1 Findings appear in The Lancet Diabetes & Endocrinology.

Originally developed to treat diabetes, GLP-1 receptor agonists mimic the action of glucagon-like peptide 1, a hormone which stimulates insulin production and lowers blood sugar levels. More recently, they have emerged as effective treatments for obesity – slowing digestion, increasing satiety and reducing hunger. 

But while the benefits of GLP-1 receptor agonists for the treatment of type 2 diabetes, obesity and cardiovascular disease are well known, their impact on chronic kidney disease (CKD) has been less certain.

Researchers conducted a meta-analysis of 11 large-scale clinical trials of GLP-1 receptor agonists involving a total of 85 373 people (79.4% with type 2 diabetes and 20.6% with overweight or obesity and cardiovascular disease but without diabetes). Seven different GLP-1 receptor agonists were investigated among the trials. 

The results showed that compared to placebo, GLP-1 receptor agonists reduced the risk of kidney failure by 16% and the worsening of kidney function by 22% (defined by a drop in estimated glomerular filtration rate – a measure of how much blood the kidneys filter clean every minute – of at least 50%). The combined reduction in the risk of kidney failure, worsening kidney function, and death due to kidney disease was 19%. 

The analysis also confirmed previous findings that GLP-1 receptor agonists protect cardiovascular health, with a 14% reduction in the risk of cardiovascular death, non-fatal heart attack, and non-fatal stroke, compared to placebo. Death by any cause was 13% lower among patients treated with GLP-1 receptor agonists.

Lead author Professor Sunil Badve, Professorial Fellow at The George Institute for Global Health and UNSW Sydney said the study expanded current knowledge about this class of drugs in key areas, including benefits in people with CKD, and in people with and without diabetes. 

“This is the first study to show a clear benefit of GLP-1 receptor agonists on kidney failure or end-stage kidney disease, suggesting they have a key role in kidney-protective and heart-protective treatment for patients with common medical conditions like type 2 diabetes, overweight or obesity with cardiovascular disease, or CKD,” he said.

“These results are particularly important for patients with chronic kidney disease. It is a progressive condition eventually leading to kidney failure requiring dialysis or kidney transplantation and is associated with premature death, mostly from heart disease. It has a significant impact on patients’ quality of life and incurs substantial healthcare costs.” 

CKD is estimated to affect one in ten people worldwide, equivalent to around 850 million people.2 It is the tenth leading cause of death and is projected to become the fifth most common cause of death by 2050.3 Diabetes, cardiovascular disease and obesity are independent risk factors for CKD and represent a major global health burden.4

Source: George Institute for Global Health

References

  1. Badve S et al. Effects of glucagon-like peptide-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2024. https://doi.org/10.1016/S2213-8587(24)00271-7
  2. Jager KJ, et al. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Kidney Int. 2019. https://doi.org/10.1016/j.kint.2019.07.012 
  3. GBD 2021 Forecasting Collaborators. Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021. Lancet. 2024. https://doi.org/10.1016/S0140-6736(24)00685-8 
  4. The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration. Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardio-metabolic risk factors between 1980 and 2010: comparative risk assessment. Lancet Diabetes Endocrinol. 2015. https://doi.org/10.1016/S2213-8587(14)70102-0 
Categories : CancerTags :

Rare Disease Sheds Light on a Side Effect of Immunotherapy

On By ModernMedia
Squamous cancer cell being attacked by cytotoxic T cells. Image by National Cancer Institute on Unsplash

A multinational collaboration co-led by the Garvan Institute of Medical Research has uncovered a potential explanation for why some cancer patients receiving a type of immunotherapy called checkpoint inhibitors experience increased susceptibility to common infections.

The findings, published in the journal Immunity, provide new insights into immune responses and reveal a potential approach to preventing the common cancer therapy side effect.

“Immune checkpoint inhibitor therapies have revolutionised cancer treatment by allowing T cells to attack tumours and cancer cells more effectively. But this hasn’t been without side effects – one of which is that approximately 20% of cancer patients undergoing checkpoint inhibitor treatment experience an increased incidence of infections, a phenomenon that was previously poorly understood,” says Professor Stuart Tangye, co-senior author of the study and Head of the Immunology and Immunodeficiency Lab at Garvan.

“Our findings indicate that while checkpoint inhibitors boost anti-cancer immunity, they can also handicap B cells, which are the cells of the immune system that produce antibodies to protect against common infections. This understanding is a critical first step in understanding and reducing the side effects of this cancer treatment on immunity.”

Insights to improve immunotherapy

The researchers focused on the molecule PD-1, which acts as a ‘handbrake’ on the immune system, preventing overactivation of T cells. Checkpoint inhibitor therapies work by releasing this molecular ‘handbrake’ to enhance the immune system’s ability to fight cancer.

The study, which was conducted in collaboration with Rockefeller University in the USA and Kyoto University Graduate School of Medicine in Japan, examined the immune cells of patients with rare cases of genetic deficiency of PD-1, or its binding partner PD-L1, as well as animal models lacking PD-1 signalling. The researchers found that impaired or absent PD-1 activity can significantly reduce the diversity and quality of antibodies produced by memory B cells – the long-lived immune cells that ‘remember’ past infections.

“We found that people born with a deficiency in PD-1 or PD-L1 have reduced diversity in their antibodies and fewer memory B cells, which made it harder to generate high-quality antibodies against common pathogens such as viruses and bacteria,” says Dr Masato Ogishi, first author of the study, from Rockefeller University.

Professor Tangye adds: “This dampening of the generation and quality of memory B cells could explain the increased rates of infection reported in patients with cancer receiving checkpoint inhibitor therapy.”

Co-author Dr Kenji Chamoto, from Kyoto University, says, “PD-1 inhibition has a ‘yin and yang’ nature: it activates anti-tumour immunity but at the same time impedes B-cell immunity. And this duality seems to stem from a conserved mechanism of immune homeostasis.”

New recommendation for clinicians

The researchers say the findings highlight the need for clinicians to monitor B cell function in patients receiving checkpoint inhibitors and point to preventative interventions for those at higher risk of infections.

Co-senior author Dr Stéphanie Boisson-Dupuis, from Rockefeller University, says, “Although PD-1 inhibitors have greatly improved cancer care, our findings indicate that clinicians need to be aware of the potential trade-off between enhanced anti-tumour immunity and impaired antibody-mediated immunity.”

“One potential preventative solution is immunoglobulin replacement therapy (IgRT), an existing treatment used to replace missing antibodies in patients with immunodeficiencies, which could be considered as a preventative measure for cancer patients at higher risk of infections,” she says.

From rare cases to insights to benefit all

 “Studying cases of rare genetic conditions such as PD-1 or PD-L1 deficiency enables us to gain profound insights into how the human immune system normally works, and how our own manipulation of it can affect it. Thanks to these patients, we’ve found an avenue for fine-tuning cancer immunotherapies to maximise benefit while minimising harm,” says Professor Tangye.

Looking ahead, the researchers will explore ways to refine checkpoint inhibitor treatments to maintain their powerful anti-cancer effects while preserving the immune system’s ability to fight infections.

“This research highlights the potential for cancer, genomics and immunology research to inform one another, enabling discoveries that can benefit the broader population,” says Professor Tangye.

Professor Stuart Tangye is a Conjoint Professor at St Vincent’s Clinical School, Faculty of Medicine and Health, UNSW Sydney.

Source: Garvan Institute of Medical Research

Categories : Neurodegenerative DiseasesTags :

Shrinking Brain Volume may be Reflective of Alzheimer’s Treatment Efficacy

On By ModernMedia
Neurons in the brain of an Alzheimer’s patient, with plaques caused by tau proteins. Credit: NIH

Brain shrinkage observed in people receiving drugs for Alzheimer’s treatment actually reflects their efficacy, suggests to a new study from University College London. The researchers analysed data from a dozen different trials of amyloid-targeting immunotherapy – including lecanemab, recently approved in the UK for Alzheimer’s treatment but not yet used by the NHS.

While brain shrinkage is usually an undesirable outcome, the team found that the excess volume loss was consistent across studies and correlated with how effective the therapy was in removing amyloid and was not associated with harm.

As a result, the researchers believe that the removal of amyloid plaques, which are abundant in Alzheimer’s patients, could account for the observed brain volume changes. And, as such, the volume loss should not be a cause for concern.

To describe this phenomenon, the research team coined a new phrase: “amyloid-removal-related pseudo-atrophy” or ARPA. The team published their findings in published in Lancet Neurology.

Senior author and Director of the UCL Dementia Research Centre, Professor Nick Fox said: “Amyloid-targeting monoclonal antibodies represent a significant therapeutic breakthrough in the treatment of Alzheimer’s disease. These agents work by binding to and triggering the removal of amyloid plaques from the brain.

“One area of controversy has been the effect of these agents on brain volumes. Brain volume loss is a characteristic feature of Alzheimer’s disease, caused by progressive loss of neurons.

“Amyloid immunotherapy has consistently shown an increase in brain volume loss – leading to concerns in the media and medical literature that these drugs could be causing unrecognised toxicity to the brains of treated patients.

“However, based on the available data, we believe that this excess volume change is an anticipated consequence of the removal of pathologic amyloid plaques from the brain of patients with Alzheimer’s disease.”

In August, the Medicines and Healthcare Products Regulatory Agency (MHRA) licensed lecanemab, for use in the early stages of Alzheimer’s disease in the UK *.

The drug works by targeting beta amyloid – a protein that builds up in the brains of people with Alzheimer’s disease and is thought to be the triggering event leading to neuronal dysfunction and cell death.

The National Institute for Health and Care Excellence (NICE) that decide whether drugs should be made available on the NHS have published draft guidance advising that the benefits of lecanemab are too small to justify the cost to the NHS. However, the decision will be reviewed following a public consultation and a second independent committee meeting later this year.

Source: University College London