CDSCO Panel Accepts Phase I Trial Data for Intas’ Denosumab Biosimilar

New Delhi: The Subject Expert Committee (SEC) under the Analgesic and Rheumatology division of the Central Drugs Standard Control Organisation (CDSCO) has reviewed and accepted the final Clinical Study Report (CSR) submitted by Intas Pharmaceuticals Ltd. for its proposed biosimilar Denosumab 120 mg/1.7 ml injection, without raising any objections.

The development was discussed during the SEC meeting held on June 24, 2025, under file number E-54043. The CSR presented data from a Phase I, randomized, double-blind, three-arm, balanced, single-dose, parallel-group clinical trial, conducted under Protocol No. 0568-19. The study aimed to establish pharmacokinetic (PK) and pharmacodynamic (PD) comparability between Intas’ biosimilar Denosumab and the reference biologics Xgeva® from Amgen Inc., USA, and Amgen Europe B.V., The Netherlands.

The trial enrolled healthy adult male volunteers and evaluated bioequivalence and safety of the biosimilar candidate in a controlled setting, an essential step in the development of monoclonal antibody-based biosimilars.

Denosumab is a fully human monoclonal antibody targeting RANKL (Receptor Activator of Nuclear factor Kappa-Β Ligand), an essential regulator of osteoclasts, which are responsible for bone resorption. The reference product, Xgeva®, is widely approved for preventing skeletal-related events (SREs) in patients with bone metastases from solid tumors, as well as giant cell tumor of bone and hypercalcemia of malignancy.

Intas Pharmaceuticals Ltd., based in Ahmedabad, Gujarat, is a vertically integrated pharmaceutical company known for its strong biologics and biosimilars pipeline. The company has a wide global presence across North America, Europe, and Asia, and is committed to providing high-quality, affordable therapies in critical areas like oncology, rheumatology, and nephrology.

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Medical Bulletin 02/August/2025

Here are the top medical news for the day:

Non-Invasive Saliva Test May Detect Early Signs of Diabetes and Obesity: Study Finds

A new study published in Applied Physiology, Nutrition, and Metabolism has found that insulin levels in saliva can be used as a non-invasive method to detect early signs of metabolic health issues, including Type 2 diabetes, obesity, and heart disease.

Hyperinsulinemia, or elevated insulin levels in the blood, is a well-established marker of poor metabolic health and a predictor of chronic diseases. While blood testing has been the standard, researchers now say that saliva testing could serve as a practical and less invasive alternative.

The study involved 94 healthy participants with a range of body sizes. After fasting, each participant consumed a standardized meal-replacement shake, provided saliva samples at multiple time points, and completed a finger-prick blood glucose test. Researchers found that individuals living with obesity had significantly higher saliva insulin levels compared to leaner participants, even though their blood glucose levels remained similar.

Dr. Hossein Rafiei, co-author of the study, highlighted another compelling finding: some lean participants also showed large spikes in saliva insulin after the meal. “The finding that some people who are lean have high insulin is intriguing. This indicates that saliva insulin may be more useful than measuring someone’s weight or waist size.”

The study also found that waist circumference had the strongest correlation with elevated saliva insulin, more so than BMI, age, or sex. “Our results also suggest that saliva insulin may be better than blood glucose at distinguishing between those who are more metabolically healthy and those who are more likely to live with hyperinsulinemia,” adds Dr. Rafiei.

Researchers hope this method could eventually lead to accessible screening tools that enable early interventions—well before chronic conditions take hold.

Reference: Hossein Rafiei and Jonathan Peter Little. 2025. Saliva insulin concentration following ingestion of a standardized mixed meal tolerance test: influence of obesity status. Applied Physiology, Nutrition, and Metabolism. 50: 1-8. https://doi.org/10.1139/apnm-2024-0532

Study Reveals Artificial Sweetener May Weaken Cancer Immunotherapy

A new study published in Cancer Discovery, a journal of the American Association for Cancer Research, has found that high consumption of sucralose—a common artificial sweetener—may impair the effectiveness of immunotherapy in cancer patients. Researchers reported that patients with melanoma or non-small cell lung cancer who consumed high levels of sucralose had worse outcomes and reduced survival compared to those with lower intake.

Sucralose is widely used as a sugar substitute in diet sodas, coffee, and other low-calorie foods. While often chosen for its ability to help manage blood sugar and weight, this new research suggests it may have unintended consequences for cancer patients undergoing immune checkpoint inhibitor therapies such as anti-PD1 treatment.

To explore this link, researchers used mouse models of adenocarcinoma and melanoma. They found that sucralose disrupted the gut microbiome, increasing bacteria that degrade arginine—an amino acid critical for T cell function. This reduction in arginine led to less effective immune responses and poorer tumor control. “When arginine levels were depleted due to sucralose-driven shifts in the microbiome, T cells couldn’t function properly,” explained lead author Dr. Abby Overacre. “As a result, immunotherapy wasn’t as effective in mice that were fed sucralose.”

However, the researchers also discovered a promising workaround. Supplementing sucralose-fed mice with either arginine or citrulline—a compound that the body converts into arginine—restored the effectiveness of immunotherapy. “That’s why it’s so exciting that arginine supplementation could be a simple approach to counteract the negative effects of sucralose on immunotherapy,” Overacre added.

To test the relevance in humans, the team analyzed dietary data from 132 cancer patients undergoing anti-PD1 therapy. Those with higher reported intake of sucralose-containing foods and drinks had consistently poorer responses across various cancer types and treatment combinations.

A clinical trial is being planned to test citrulline supplementation in patients receiving immunotherapy.

Reference: Kristin M. Morder, Madison Nguyen, Drew N. Wilfahrt, Zakaria Larbi. Dahmani, Ansen BP. Burr, Bingxian Xie, Michael Morikone, Hector Nieves-Rosado, William G. Gunn, Drew E. Hurd, Hong Wang, Steven J. Mullett, Kaitlin Bossong, Stacy L. Gelhaus, Dhivyaa Rajasundaram, Lawrence P. Kane, Greg M. Delgoffe, Jishnu Das, Diwakar Davar, Abigail E. Overacre-Delgoffe; Sucralose consumption ablates cancer immunotherapy response through microbiome disruption.. Cancer Discov 2025; https://doi.org/10.1158/2159-8290.CD-25-0247

New Tool Can Calculate Heart Age and Reveal Hidden Cardiovascular Risks: JAMA

Your heart could be aging faster than the rest of your body, according to new research published in JAMA Cardiology. The study, conducted by researchers at Northwestern University Feinberg School of Medicine, found that many U.S. adults have a “heart age” several years older than their actual age. The age gap, the researchers noted, is even more pronounced in men than in women.

To make these findings more accessible and actionable, the research team developed a free online tool called the PREVENT Risk Age Calculator. This tool estimates a person’s heart age based on key health information such as cholesterol levels, blood pressure, BMI, medications, smoking habits, and diabetes status. Instead of presenting risk as a percentage, the calculator expresses it as an age, making it easier to understand.

“Heart age, or PREVENT age, may be particularly useful for patients and clinicians and be more effective in preventing heart disease,” said senior author Dr. Sadiya Khan, the Magerstadt Professor of Cardiovascular Epidemiology at Northwestern. “It translates complex information about the risk of heart attack, stroke or heart failure over the next 10 years into a number that is easier to understand and compare with one we are all familiar with – your actual age.”

To validate the tool, researchers analyzed health data from over 14,000 adults aged 30 to 79 who had no prior history of cardiovascular disease. They calculated heart ages and compared them to the participants’ real ages. The findings showed that the average heart age among women was 55.4—nearly four years older than their chronological age of 51.3. Men, on the other hand, had an average heart age of 56.7, seven years higher than their chronological age of 49.7.

While Dr. Khan noted that a one- or two-year gap may not be significant, a difference of five years or more could be cause for concern. “We hope this new heart age calculator will help support discussions about prevention and ultimately improve health for all people,” he said.

Researchers acknowledged that the definition of “optimal risk” could affect results and that wider testing is needed to determine how easily the tool is understood and adopted in clinical settings.

Reference: Krishnan V, Huang X, Perak AM, et al. PREVENT Risk Age Equations and Population Distribution in US Adults. JAMA Cardiol. Published online July 30, 2025. doi:10.1001/jamacardio.2025.2427

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Family alleges negligence after newborn dies at Nahan Govt Hospital

Nahan: A newborn baby passed away at Dr. YS Parmar Government Medical College and Hospital in Nahan, with the family accusing doctors of alleged medical negligence.

The incident has sparked outrage after a video surfaced on social media showing the infant’s maternal aunt detailing the alleged lapse.

In the video, the infant’s maternal aunt mentioned that her pregnant sister was admitted to the hospital on July 24. She claims that attending doctors administered doses of labour-inducing medication at 2 am, 6 am, and 10 am. However, despite experiencing intense labour pains for over ten hours, the pregnant woman’s cervical dilation reportedly did not progress beyond two centimetres.

Also Read: Probe ordered after gauze found inside woman’s abdomen after c-section

Despite the evident lack of progress and increasing risk, she alleged, the doctors did not consider a caesarean section or other urgent intervention. By the time medical staff took further action, the baby had already died in the womb.

Further allegations include the absence of on-duty doctors during critical nighttime hours, as well as a lack of essential medical equipment. She stated that the hospital did not have a working foetal heartbeat monitor or a 3D ultrasound machine — both considered vital in managing high-risk deliveries.

She added that the negligence not only resulted in the newborn’s death but also caused immense physical and emotional trauma to her sister. Speaking to Tribune India, Dr Sangeeta Dhillon, Senior Medical Superintendent at the medical college, said no formal complaint had been received in writing as of now. “If a complaint is submitted, action will be taken as per protocol,” she added.

Also Read: Stillbirth due to treatment delay- TN Govt to pay Rs 5 lakh compensation

Medical Dialogues had previously reported that the State Human Rights Commission (SHRC) has directed the Tamil Nadu Government to pay Rs 5 lakh compensation to a woman who delivered a stillborn baby due to allegedly delayed medical treatment at Murukkeri Primary Health Centre (PHC) in Villupuram.

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Cancer immunotherapy linked to rare liver complication, study warns

A global study reveals that cutting-edge cancer immunotherapies, while lifesaving, carry a hidden risk: they may trigger cholestasis, a serious liver condition where bile flow stalls. Analyzing 634 patient reports from global drug-safety databases (FAERS and VigiBase), scientists found immunotherapy patients had a significantly higher risk of cholestasis than chemotherapy recipients. Those under 65 faced greater danger, and women developed symptoms weeks earlier than men (Median 1.17 vs. 1.90 months).

Anti-PD-1 drugs (e.g., pembrolizumab) and combination therapies posed the highest risk. In mice, combined anti-CTLA-4/anti-PD-L1 drugs caused severe bile duct injury. Molecular analysis linked the condition to disrupted bile acid metabolism and inflammation pathways.

“This isn’t about abandoning immunotherapies-they save lives,” stresses senior author Peng Luo, PhD, of Southern Medical University. “But we must monitor liver function aggressively, especially in the first month for women and young adults. Catching cholestasis early prevents irreversible damage.”

Surprisingly, cholestasis often occurred without classic hepatitis symptoms, suggesting routine liver tests alone may miss it. The team urges adding bile acid level checks to standard monitoring.

Reference:

Yan, Xinronga,†; Li, Zhengruib,†; Jiang, Aiminc,†; Chen, Jinghonga,†; Huang, Xufengd,e; Hajdu, Andrásd; Wong, Hank Z.H.f; Cheng, Quang,h,*; Zhang, Jiani,*; Lin, Anqia,*; Luo, Penga,*. Immunotherapy-induced cholestasis in cancer: insights from the two real-world pharmacovigilance databases of FAERS and vigiBase. International Journal of Surgery ():10.1097/JS9.0000000000002607, June 05, 2025. | DOI: 10.1097/JS9.0000000000002607.

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Study finds living in rural environments in first 5 years of life could be a risk factor for developing type 1 diabetes

New research to be presented at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria (15–19 September) suggests that living in a rural environment in the first five years of life could increase the risk of developing type 1 diabetes compared with living in urban environments.

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Study finds rising cannabis use among Black and Hispanic men with chronic illness

Cannabis use is gaining popularity in the United States, driven by growing legalization, public acceptance and diverse methods of consumption.

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The power of play in early childhood

Play is how young children make sense of the world. Whether with dolls, blocks, trains, or playdough, children use play to explore, experiment, and learn. In early childhood, it is essential that children have at least an hour of open-ended play each day, as recommended by research. During this time, they should be encouraged to ask questions, test ideas and engage in creative thinking. Play is not just fun — it is foundational. Play supports cognitive growth, language and communication skills, social and emotional development, physical coordination, creativity, and overall school readiness.

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Scientists identify shared biological roots of long COVID and chronic fatigue syndrome

In recent years, doctors and scientists are increasingly studying long-lasting illnesses that begin after someone recovers from an infection. Two of the most well-known examples are long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

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‘And’ vs. ‘Then’: What words in online reviews tell us about hospital visits

Can simple words like “and” or “then” in online reviews help health care providers learn about their patients’ experiences?

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Methylglyoxal Independently Contributes to Liver Fibrosis in Obesity: Study

A new study has determined that increased concentrations of methylglyoxal (MGO), a potent reactive byproduct of glucose metabolism, can independently cause the onset of liver fibrosis among obese individuals. The finding is consistent with mounting evidence indicating that MGO and similar compounds not only initiate inflammation and produce deleterious advanced glycation end products (AGEs), but also are key players in liver injury involved with metabolic dysfunction-associated steatotic liver disease (MASLD).

The research, which quantified plasma concentrations of MGO, glyoxal (GO), and 3-deoxyglucosone (3-DG), had significant correlations with severity of liver fibrosis, even in non-type 2 diabetic subjects. The study was conducted by Oluwatomisono I. and colleagues published in the journal of Diabetes Obesity and Metabolism.

264 severely obese subjects undergoing bariatric surgery were studied as part of the BARIA cohort. Among the participants, 22% had type 2 diabetes, 77% were female, the median age was 47 years (IQR: 39–54 years), and the median BMI was 39 kg/m² (IQR: 36–41 kg/m²). Plasma concentrations of MGO, GO, and 3-DG were measured in a research setting using ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Liver fibrosis was assessed by two different approaches: the non-invasive Fibrosis-4 (FIB-4) Index and direct liver histology score from biopsies.

Key findings

  • Plasma MGO levels were significantly increased in people with type 2 diabetes (median: 288 nmol/L; IQR: 257–334 nmol/L) versus those without diabetes (median: 238 nmol/L; IQR: 212–279 nmol/L). MGO also rose higher in men (267 nmol/L; IQR: 236–301 nmol/L) than in women (245 nmol/L; IQR: 214–288 nmol/L).

  • The same tendencies were seen for GO and 3-DG, suggesting that dicarbonyl stress is greater in men and people with diabetes.

  • Plasma concentrations of MGO, GO, and 3-DG were positively correlated with higher scores for FIB-4 Index, a very high correlation with liver fibrosis.

  • That is, correlation coefficients (rho) were 0.21 for MGO, 0.29 for GO, and 0.25 for 3-DG, and all were statistically significant (p < 0.05).

  • In multiple linear regression models controlling for several potential confounders (age, sex, BMI, smoking status, alcohol intake, hypertension, insulin resistance, HbA1c, and fasting glucose), the relationship between MGO and the FIB-4 Index continued to hold strong.

This study highlights dicarbonyl stress especially from methylglyoxal as a significant and independent contributor to liver fibrosis in obese individuals, even in the absence of diabetes.

Reference:

Akinrimisi, O. I., Koning, M., Scheijen, J. L. J. M., Meijnikman, A. S., Sindhunata, D. P., Bruin, S., van de Laar, A., Franken, R., Acherman, Y., Gerdes, V. E. A., Nieuwdorp, M., Schalkwijk, C. G., & Hanssen, N. M. J. (2025). Higher plasma dicarbonyl levels are associated with liver fibrosis in obese individuals. Diabetes, Obesity & Metabolism. https://doi.org/10.1111/dom.16643

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