Prince Aly Khan Hospital

INTRODUCTION:Obesity is highly prevalent in India, creating an urgent need for effective management interventions. The study hypothesizes that synthetic semaglutide has comparable safety and efficacy to the innovator drug when used in obese adults for weight management. METHODS:A phase III multicenter randomized active-controlled non-inferiority trial enrolled adults with obesity across 19 centers in India. Subjects were randomized to the test arm receiving synthetic semaglutide (Alkem Laboratories Limited) or the reference arm administered with innovator semaglutide (Wegovy®, Novo Nordisk) over 24 weeks in a 2:1 ratio. The primary efficacy endpoint was the percentage change in body weight,24 weeks post-intervention. Synthetic semaglutide was established to be non-inferior if the lower bound of the one-sided 97.5% confidence interval for the between-group difference did not exceed 4.5%. RESULTS:Of the 249 randomized participants, 246 (98.8%) completed the study. Mean percentage weight loss after 24 weeks was -14.39 ± 4.17% in the test arm and -14.61 ± 4.36% in the reference arm. The least square-mean difference was 0.15% (-0.93 to 1.24), meeting the predefined non-inferiority criterion. Weight loss >10% was achieved by 86.67% (n=143) in the test arm and 83.95% (n=68) in the reference arm (p = 0.5666), while >15% weight loss occurred in 38.79% (n=64) and 40.74% (n=33), respectively (p = 0.7683). Mean body mass index decreased by -4.93 ± 1.43 kg/m² in the test arm and -5.00 ± 1.50 kg/m² in the reference arm (p = 0.7128). Treatment-emergent adverse events were reported in 55.42% (n=92) of test-arm participants and 54.22% (n=45) of reference-arm participants. CONCLUSIONS:Test semaglutide demonstrated non-inferior efficacy, comparable safety, and similar tolerability to the innovator product.

Abstract Background This study evaluated the efficacy and safety of generic semaglutide compared with innovator Semaglutide in Indian adults with type 2 diabetes mellitus (T2DM). Methods This Phase 3, multicenter, randomized, active-controlled, non-inferiority trial enrolled 320 adults with T2DM inadequately controlled on metformin. Participants were randomized 1:1 to receive either generic semaglutide (Alkem laboratories Ltd.) or innovator Inj. semaglutide (Novo Nordisk) for 24 weeks in step-wise dose escalation from 0.25 mg/week to 2 mg/week. The primary endpoint was change in HbA1c from baseline to Week 24. Secondary endpoints included changes in fasting and post-prandial glucose, body weight, and proportion of patients achieving HbA1c < 7.0%. Safety assessments included adverse events, hypoglycemia, various laboratory parameters. Results Of 320 participants randomized, 313 completed the study. Baseline demographic and clinical characteristics were comparable between groups. At Week 24, both treatments achieved significant HbA1c reductions (mean − 2.20%), with generic semaglutide demonstrating non-inferiority to the reference. Reductions in body weight, fasting and post-prandial glucose were similar between arms. A total of 86.62% of participants achieved HbA1c < 7.0%. Safety profiles were comparable, with predominantly mild-to-moderate adverse events and no treatment-related serious adverse events. Conclusion Generic semaglutide demonstrated non-inferior efficacy and comparable safety to innovator Semaglutide in Indian adults with T2DM inadequately controlled on metformin, offering an effective and accessible therapeutic option in resource-limited settings.

Introduction: The simultaneous rise of hypertension and diabetes in Indian patients necessitates effective management strategies to prevent severe complications. The study addresses the limited understanding of hypertension management in diabetic patients within the Indian clinical context, highlighting gaps in region-specific data on expert perceptions and preferred strategies. Aim: To assess Indian physicians’ perceptions and practices regarding the impact of hypertension in patients with diabetes and the most appropriate strategies for managing it. Materials and Methods: The present study was a cross-sectional, questionnaire based electronic survey. A total of 1618 physicians throughout India were invited to participate in an online survey and virtual meetings. The study questionnaire had two sections. Section 1 consisted of four questions focusing on the detrimental effects of hypertension on diabetes. Section 2 included seven questions regarding appropriate management approaches for hypertension. The data collected was analysed using Microsoft Excel 2019 and presented as frequency. Results: Majority of the physicians (39.9%) were from Western region. The majority of participants in this survey had 10-20 years of experience (n=504, 41.2%) and practiced in their clinic (n=541, 44.3%). The expert panel reported that cardiac events (48.22%) were the most common consequence of hypertension in diabetic patients. They recommended telmisartan (85.9%), amlodipine (64.7%), and metoprolol (76.0%) as preferred treatments for managing diabetes with hypertension and cardiovascular Co-morbidities. For patients with diabetes, hypertension, and Chronic Kidney Disease (CKD), telmisartan (84.0%), amlodipine (63.4%), and hydrochlorothiazide (63.1%) were favoured. Additionally, 51.3% of diabetologists did not recommend the use of dual RAAS inhibitors (ACE inhibitors+ARB). In a patient with diabetes, hypertension and a history of stroke, if Blood Pressure (BP) remains uncontrolled on an optimal ARB dose, Calcium Channel Blockers (CCBs) should be added as a second-line therapy. Conclusion: Appropriate management strategies, such as enhancing medication adherence, patient education, and selecting effective treatments, can prevent the detrimental effects of hypertension in patients with diabetes and Co-morbidities. Indian diabetologists typically prefer ARBs as the first-line therapy and CCBs, beta-blockers, or diuretics as second-line options. The most commonly chosen medications include telmisartan, amlodipine, metoprolol, and hydrochlorothiazide. As a second-line treatment, CCBs are particularly preferred for patients who have both diabetes and CKD.

Background Resistance or intolerance to the available tyrosine kinase inhibitors (TKIs) remains a treatment challenge for patients with chronic myeloid leukaemia. We aimed to report the safety, antileukaemic activity, and pharmacokinetics of oral vodobatinib, a novel selective BCR::ABL1 TKI, in patients with Philadelphia chromosome- positive (Ph-positive) chronic myeloid leukaemia who previously received at least three TKIs, including ponatinib and asciminib. Methods This open-label, multicentre, phase 1/2 trial was conducted at 28 clinical sites across ten countries (Belgium, France, Hungary, India, Italy, Romania, South Korea, Spain, UK, and the USA). Patients aged 18 years or older with Ph-positive chronic myeloid leukaemia or acute lymphoblastic leukaemia (eligible only for the phase 1 study), and an Eastern Cooperative Oncology Group performance status of 2 or lower were eligible. Phase 1 included patients who previously received at least three TKIs or had no other available treatment options. Phase 2 required patients to have treatment resistance or intolerance (or both) with loss of response to at least three TKIs and previous ponatinib use. A key exclusion criterion for both phases was presence of the Thr315Ile mutation. Patients self-administered oral vodobatinib (12-240 mg) once per day for each 28-day treatment cycle and for up to 60 months (ie, 65 cycles) unless patient discontinuation due to adverse events, progressive disease, lost to follow-up, or death. The primary endpoints were to determine the maximum tolerated dose (based on dose-limiting toxicities in phase 1) and antileukaemic activity of vodobatinib (ie, major cytogenetic response for chronic-phase and major haematological response for accelerated-phase or blast-phase in phase 2). Assessment of vodobatinib safety, activity, and pharmacokinetics were determined based on the pooled analysis of data from the phase 1 and 2 studies. This trial is registered with ClinicalTrials.gov, NCT02629692 (active). At data cutoff (July 15, 2023), phase 2 enrolment was closed early on June 22, 2023, due to recruitment-related challenges. Findings 78 patients were enrolled and received at least one vodobatinib dose (safety and efficacy analysis set). Between April 6, 2017, and June 20, 2023, phase 1 enrolled 58 patients and phase 2 enrolled 20 patients between March 3, 2020, and March 29, 2023. We included 66 (85%) patients with chronic-phase, eight (10%) with accelerated-phase, and four (5%) with blast-phase chronic myeloid leukaemia. 43 (55%) of 78 patients were male and 35 (45%) were female. The median age was 590 years (IQR 470-660). The median follow-up was 223 months (IQR 111-439). Two patients receiving vodobatinib 240 mg had dose-limiting toxicities (one had grade 3 dyspnoea and the other had grade 2 fluid overload), thus the 204 mg dose was considered to be the maximum tolerated dose. 73 (94%) patients had one or more treatment-emergent adverse events, with most events being haematological or gastrointestinal that were grade 2 or lower in severity. Grade 3 or higher treatment-emergent adverse events occurred in 47 (60%) patients and included thrombocytopenia (14 [18%]), neutropenia (10 [13%]), anaemia (nine [12%]), and increased lipase (eight [10%]). Seven (9%) patients died during the study; one death was considered related to treatment by the clinical investigator. At data cutoff, major cytogenetic response was observed in 44 (70%) of 63 patients with chronic-phase chronic myeloid leukaemia, of which 12 (75%) of 16 patients in the phase 2 study had major cytogenetic response. For patients with accelerated-phase chronic myeloid leukaemia, six (86%) of seven patients had a major haematological response (median duration 178 [IQR 102-243]) at data cutoff; major haematological response was observed in three (100%) evaluable patients in the phase 2 study. Major haematological response was reached by two (50%) of four patients with blast-phase chronic myeloid leukaemia and the median duration of response was 62 months (IQR 32-93); no blast-phase patients were enrolled in the phase 2 study. Interpretation Pooled analysis of the phase 1 and 2 studies showed clinically meaningful antileukaemic activity of vodobatinib and a tolerable safety profile in patients with advanced chronic myeloid leukaemia who previously received multiple TKIs, including ponatinib and asciminib, addressing an otherwise unmet clinical need. The phase 2 study was statistically underpowered and warrants further investigation in a phase 3, randomised controlled trial and in an earlier treatment setting of the disease. Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Oral cancer is one of the most common cancers seen in the Indian subcontinent. Its primary treatment is surgery with or without adjuvant treatment. Despite advances in science, prognosis and overall survival has not yet chanced over the past two decades. Pathologically proven regional lymph node metastasis adversely affects the prognosis. This study was conducted to evaluate the predictive factors for lymph node metastasis in Stage I and II oral squamous cell carcinoma (OSCC) with distinct emphasis on tumor budding and worst pattern of invasion. This is a prospective observational study was done at a tertiary care center, Prince Aly Khan Hospital, Mumbai, over a period of 22 months (March, 2020 to December, 2021). We analyzed 237 patients of early OSCC for clinicopathological parameters (age, trismus, differentiation, depth of invasion, tumor budding, worst pattern of invasion). Chi Square test and logistic regression model were used for data evaluation. Statistical Package for Social Sciences, version 21.0 IBM Corporation USA for Microsoft Windows, was used for data analysis. This study reported statistically significant predictive factors for lymph node metastasis viz. tumor budding (OR 30.8 95