Tuesday, June 9, 2026
Monday, June 8, 2026
Gilead, Merck HIV Combination Meets Primary Endpoint in Two Phase 3 Trials
Novel Investigational Combination Pairs Merck’s Islatravir, a Next-Generation Nucleoside Analog with Distinct Mechanisms of Action, Including Reverse Transcriptase Translocation Inhibition, with Gilead’s Lenacapavir, a First-in-Class Capsid Inhibitor that Disrupts HIV at Multiple Stages of its Lifecycle –
– Islatravir/Lenacapavir has the Potential to be the First Approved Long-Acting Oral HIV Treatment Taken Once-Weekly –
https://sg.finance.yahoo.com/news/gilead-merck-announce-positive-topline-203500265.html
GSK in talks to buy cancer biotech Nuvalent for more than $9 billion: FT
GSK is reportedly in talks to acquire clinical‑stage cancer biotech Nuvalent for more than $9 billion, according to the Financial Times; the deal—if true—would mark a major expansion of GSK’s oncology pipeline. Nuvalent’s market cap stands around $8–8.5 billion
https://www.globalbankingandfinance.com/gsk-talks-buy-cancer-biotech-nuvalent-9-billion-ft-reports/
'Primitive Reflexes May Predict Dementia'
- Frontal release signs predicted higher 7-year dementia risk in cognitively normal adults.
- These signs are simple neurologic exam findings associated with brain injury or neurodegeneration.
- Frontal release signs include primitive grasp, snout, and rooting reflexes.
Primitive or regressive reflexes -- known as frontal release signs -- later in life were associated with increased dementia risk, a longitudinal study of cognitively normal older adults showed.
In adults with intact cognition, the presence of two or more frontal release signs was associated with a significantly higher risk of progressing to dementia over 7 years (HR 1.78, 95% CI 1.02-3.09), reported Lauren Bojarski, DO, MS, of West Virginia University in Morgantown, and colleagues in JAMA Network Open.
Frontal release signs are present in newborn children and gradually disappear as the brain matures in early life. They include the Myerson sign (an inability to resist blinking when repeatedly tapped between the eyebrows), and grasp, snout, rooting, and palmomental reflexes. Reappearing signs are associated with brain injury or neurodegeneration and can be seen in late-life dementia.
Signs of frontal release are easy to assess and traditionally have been considered part of a standard neurologic exam. While individual signs have shown relatively low sensitivity and specificity for detecting injury or degeneration, a meta-analysis of 29 studies found that people with dementia were up to 16 times more likely to exhibit frontal release signs, with the grasp reflex showing the strongest link.
"As biomarkers become increasingly integrated into the dementia diagnostic pathway, we must remember that clinical acumen remains paramount. A meticulous neurologic examination yields invaluable diagnostic insight, yet we are seeing a concerning decline in the foundational neurology rotations essential for training the next generation of clinicians," Bojarski said.
"By demonstrating the enduring utility of the clinical exam and prioritizing these bedside skills in medical education, we can ultimately foster greater diagnostic accuracy and therapeutic confidence," she told MedPage Today.
Bojarski and co-authors followed 873 older adults from the University of Kentucky Alzheimer's Disease Research Center (ADRC) cohort in Lexington from 2005 to 2024. Participants were cognitively intact (672 participants) or had mild cognitive impairment (201 participants) at baseline; they had a mean age of 76.9 and an average of 16.1 years of education. Most (60.4%) were women.
Follow-up was 7.2 to 7.5 years on average in the cognitively intact group, and 4.0 to 4.4 years in the group with mild cognitive impairment.
Participants had at least two assessments that included standard protocols involving frontal release signs. Each annual evaluation included a medical history, a physical examination, and an extensive battery of neuropsychological tests of cognitive status.
At baseline, participants were classified as positive or negative for frontal release signs; those who had two or more signs were considered positive. In the intact cognition group, 8.8% were positive for frontal release signs; in the group with mild impairment, that proportion was 23.9%.
In the cognitively intact group, 25.4% of people with two or more frontal release signs progressed to dementia compared with 14.5% of people with one or no signs. Models adjusted for baseline age, sex, and education showed that mean scores in memory and executive domains worsened in this group over time.
Among participants with mild impairment at baseline, there was no difference in domains. No significant relationship between frontal release signs and dementia risk emerged.
This study was based on findings from a single ADRC, Bojarski and colleagues acknowledged. The cohort included people with relatively homogenous racial demographics and high education levels.
Frontal release signs can support tests and biomarkers to help determine who might develop dementia, the researchers pointed out. "Classic neurologic examination techniques like checking frontal release are gradually being replaced by sophisticated biomarkers and genetic testing, yet the importance of the neurologic exam for interpreting such biomarkers has never been greater," observed co-author Gregory Jicha, MD, PhD, of the University of Kentucky.
"We should not lose the art of the neurologic exam, as it adds incredibly to our diagnostic formulation," Jicha told MedPage Today. "We hope the future generations of neurologists do not simply look at a lab value to diagnose and treat, but rather that they fully examine and understand the patient and their neurologic condition in order to provide optimal care."
Disclosures
This study was supported by a grant from the National Institute on Aging, which funds the University of Kentucky Alzheimer's Disease Research Center.
Bojarski reported no conflicts of interest. Jicha disclosed relationships with Alnylam, Cognition Therapeutics, Eisai, and Novo Nordisk. Other study authors had no conflicts.
Tolerability Concerns for GLP-1/Glucagon Agonist in Obesity, MASLD
Treatment with survodutide led to significant weight loss and reductions in liver fat in phase III trials of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), but about a fifth of patients quit the investigational glucagon and GLP-1 receptor dual agonist due to adverse events.
Obesity Trial
In the SYNCHRONIZE-1 trial of people with obesity but without diabetes, mean body weight loss by week 76 with treatment plus lifestyle modification counseling reached 12.2% in the 3.6-mg once-weekly survodutide group and 13% in the 6.0-mg once-weekly group as compared with 5.4% with placebo, reported Carel le Roux, MBChB, PhD, of the University College Dublin School of Medicine.
"Body weight reduction with survodutide was driven predominately by loss of fat tissue," le Roux said at the American Diabetes Association (ADA) Scientific Sessions. The findings were simultaneously published in the New England Journal of Medicine.
However, gastrointestinal adverse events -- primarily nausea, vomiting, diarrhea, and constipation -- occurred in 80.9-89.7% of the survodutide groups and in 47.9% of the placebo group. These events led to 17.8-20.2% of the survodutide groups discontinuing the study treatment compared with 2.9% of the placebo group. No deaths were reported.
Obesity medication development is entering a new era of combining GLP-1 agonists with other agonists of glucagon, gastric inhibitory polypeptide (GIP), or both.
"The development of glucagon receptor-GLP-1 receptor dual agonists to enhance the relative potency of the agonists at these receptors has been challenging, particularly with respect to net effects on glucose homeostasis," the authors wrote. "In this trial, treatment with survodutide did not increase glycated hemoglobin levels in participants without diabetes mellitus; a previous phase 2 trial involving persons with obesity and type 2 diabetes showed that survodutide significantly reduced glycated hemoglobin levels."
The double-blind trial was conducted at 116 clinical sites across 14 countries. All 725 participants had either a BMI of at least 30 or at least 27 with an obesity-related complication other than diabetes. The cohort averaged 47.1 years of age, baseline BMI of 37.9, and body weight of 239.9 lb (108.8 kg). Slightly more than 40% of participants were men.
Participants were randomized 1:1:1 to once-weekly survodutide doses adjusted up to 3.6 mg or 6 mg or placebo. Patients were also encouraged to follow a reduced-calorie diet and to exercise.
Dose flexibility was initially limited to weeks 16 to 32 after randomization, and participants were told to discontinue the study treatment if three or more doses were missed due to gastrointestinal reasons or other causes.
"This study was set up specifically to be very rigid," le Roux said, explaining the high drop-out rate. "We wanted a rigorous result, we wanted an end result that you look at and say, 'I trust these numbers.' But sometimes, you can overshoot. Sometimes in your pursuit of rigorous results, we made it so difficult for patients to stay in this study that actually they had to step out because they couldn't increase the dose because of the forced titration."
"That also allows you and me to go back to clinic next week and think about what are the benefits and risk-benefit ratio between being very rigid and having more flexibility. Thinking about how we can keep people in our clinical trials but also our clinical practice ... and be more gentle with our patients," he noted.
MASLD Study
Survodutide also showed benefit for MASLD patients with obesity, according to the phase III SYNCHRONIZE-MASLD study, also presented at ADA.
Among 216 adults, 68.5% of survodutide-treated patients and 28.6% of placebo-treated patients had at least 30% reduction in MRI-proton density fat fraction-assessed liver fat content in the treatment regimen estimand by week 48 (P<0.0001) -- a degree of reduction previously linked to a higher likelihood of histologic improvement and resolution of metabolic dysfunction-associated steatohepatitis (MASH).
These data "suggest the potential for survodutide treatment to support meaningful improvement in several of the proposed drivers of MASH and hepatic fibrosis, addressing an area of high unmet need," a team led by Lee Kaplan, MD, PhD, of the Obesity and Metabolism Institute in Boston, wrote in a simultaneously published paper in Nature Medicine.
The average body weight reduction over 48 weeks was 8.7% with survodutide and 1.4% with placebo (P<0.0001) in the same treatment regimen estimand used in the SYNCHRONIZE-1 trial, a conservative assessment with missing data in the survodutide arm assumed to be similar to that in the placebo arm.
Gastrointestinal events in this study were also commonly reported during the dose-escalation phase but were generally of mild-to-moderate severity. Still, 19.9% of participants in the survodutide group discontinued treatment versus 4.3% of those in the placebo group.
Participants, who were recruited from the U.S. and Spain, all had MASLD with evidence of liver inflammation or fibrosis by noninvasive tests or biopsy-confirmed MASH. Participants were randomized 2:1 to treatment with survodutide 6 mg once weekly or placebo.
Survodutide is also being studied in two global phase III clinical trials -- LIVERAGE and LIVERAGE-Cirrhosis -- investigating the efficacy and safety of survodutide in adults with MASH and stage 2 or 3 fibrosis and in those with compensated MASH cirrhosis (stage 4 fibrosis).
Disclosures
The trial was funded by Boehringer Ingelheim.
Le Roux disclosed relationships with AbbVie, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Currax Pharmaceuticals, Eli Lilly, F. Hoffman-La Roche AG, Johnson & Johnson, Medscape, Medtronic, Metsera, Morphic Therapeutic, Novo Nordisk, Nymble, Olympus, Pfizer, and Zealand Pharma A/S.
Kaplan reported relationships with Altimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Dexligo, Dil Figaro, Eli Lilly, Helicore, Johnson & Johnson, Kallyope, The Last Food Fight, MetaVia, Neurogastrx, Novo Nordisk, Optum Health, Oxford Medical Products, Perspectum, Pfizer, Roche/Genentech, Skye Bioscience, State 4 Therapeutics, Structure Therapeutics, and Wave Life Sciences.
'Iran, allies can open new fronts, deputy chief of Khamenei's office warns'