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Aim This study aimed to demonstrate biosimilarity between Lupin’s Pegfilgrastim versus Neulasta with respect to pharmacokinetic (PK), pharmacodynamic (PD), immunogenicity, and safety profiles. Methods This double-blind, randomised, single-dose, two-sequence, two-treatment, two-period, crossover, comparative PK and PD study enrolled healthy subjects aged 18 to 45 years. The test product was Lupin’s Pegfilgrastim and the reference product was U.S.-licensed Neulasta. Blood samples were collected at different time points for assessment of PK, PD, and immunogenicity. Primary objectives included comparing the relative bioavailability and the pharmacodynamic effect of the two products. Secondary objectives included assessing immunogenicity, safety and tolerability. Biosimilarity was concluded if the 90% confidence interval (CI) of the ratio of the geometric least-squares mean (LSM) for PK and PD parameters were within 80 to 125%. Results The geometric mean ratios of Lupin’s Pegfilgrastim and Neulasta for primary PK parameters were C [94.37 (89.53 to 99.47%)], AUC [94.76 (89.83 to 99.95%)] and AUC [94.82 (89.90 to 100.02%)], and for primary PD parameters were ANC_C [100.59 (98.96-102.25%)] and ANC_AUEC [100.51 (99.18,101.85%)]. The corresponding 90% CIs were within the pre-defined equivalence limit of 80% and 125%. The incidence of ADA formation was similar between patients receiving Lupin’s Pegfilgrastim and Neulasta. No new safety concerns were observed. Conclusion This study establishes biosimilarity of Lupin’s Pegfilgrastim and Neulasta with respect to PK and PD profiles. No clinically meaningful differences were observed between the biosimilar and the reference product in terms of immunogenicity, safety, and tolerability profiles.

Introduction: The present study compared the efficacy, safety, and immunogenicity of the biosimilar darbepoetin alfa to the reference innovator darbepoetin alfa in the treatment of anemia in chronic kidney disease (CKD) patients. Materials and Methods: Out of 140 randomized individuals, 107 individuals were administered biosimilar darbepoetin alfa (study arm) and 33 individuals received reference innovator darbepoetin alfa (reference arm). Primary objective evaluated was hemoglobin responder rate for individuals achieving >1 g/dL rise in Hb from baseline to week 8. The secondary objectives were proportion of individuals achieving rise in hemoglobin (>1 g/dL rise from baseline) at week 24 to assess the proportion of individuals maintaining mean Hb within target range and evaluation of safety. Results: The hemoglobin responder rate for individuals achieving >1 g/dL rise in Hb from baseline to week 8 was similar in both the study and reference arms (56 [62.92%] and 22 [70.97%]). Overall, 86.27% individuals treated with biosimilar darbepoetin alfa achieved hemoglobin rise >1 g/dl as compared to 86.67% individuals in the reference darbepoetin arm at 24 weeks. Individuals maintaining Hb value within the target range at the end of week 24 were also similar in both the arms (60.80% and 60.00% in study and reference arms, respectively). There were 147 treatment emergent adverse events (34.58% in the study arm and 42.42% in the reference arm). Conclusion: The biosimilar darbepoetin alfa (DarbeRelTM) showed clinical biosimilarity to reference innovator darbepoetin alfa in anemia of CKD.

INTRODUCTION: The present study for biosimilar trastuzumab was a multicentric, randomized, two-arm parallel-group, comparative phase III study in patients with metastatic breast cancer. MATERIALS AND METHODS: Stage I of the study was conducted among 42 participants with equal distribution in the study and reference arm. After a loading dose of 8 mg/kg trastuzumab was administered intravenously on day 1 of the first cycle; serum samples were obtained at 0, 1.5 (end of IP infusion), 3, 6, 8, 24, 96, 168, and 336 h after the first infusion for the first cycle only. Cmax and AUC0–336 were calculated for a single dose. Stage II enrolled a total of 106 patients across 20 centers who were randomized to receive biosimilar trastuzumab (study trastuzumab) or the reference trastuzumab with paclitaxel. The primary endpoint of the objective response rate (ORR) was analyzed after last the dosed participant had completed 25-week evaluation. The secondary outcome measures included time to tumor progression, progression-free survival and overall survival at week 48, and safety evaluation. RESULTS: For reference and study trastuzumab products, mean Cmax of 229.02 and 210.68 μg/mL and AUC0–336 of 24298.29 and 25809.33 (μg × h/mL), respectively, were obtained. The efficacy results demonstrated that study trastuzumab and reference trastuzumab had comparable ORR (48.44% vs. 44.44%). The proportions of participants showing complete response and partial response in each arm were found to be comparable. There were 56 (68.29%) participants in the study arm and 13 (59.09%) participants in the reference arm who had at least one adverse event during the study. Immunogenicity assessment also revealed no participants with positive antibody titer in any of the study arms. CONCLUSION: The pharmacokinetics, overall response rate at 25 weeks, and safety of the biosimilar trastuzumab was comparable to the reference trastuzumab.

Objectives: Tenecteplase (TNK) is an established third-generation class 1A thrombolytic. The objective of the present study was to establish clinical biosimilarity of TNK biosimilar in a comparative phase III study with the reference product in the patients of ST elevation myocardial infarction (STEMI). Materials and Methods: In the double-blind, randomized, comparative clinical study 105 individuals were enrolled (70 in biosimilar TNK arm and 35 in the reference arm). Primary endpoint was thrombolysis in myocardial infarction (TIMI) 3-flow rate of the infarct-related artery at 90 min and all-cause mortality rate at 30 days' post dosing. Secondary endpoints considered were 50% resolution of elevated ST segment at 90 min, re-infarction till day 30, change in the left ventricular ejection fraction at day 30, events of ventricular tachyarrhythmias till day 30, and comparative pharmacokinetics. Immunogenicity was assessed along with the evaluation of safety at day 30. Results: TIMI grade 3-flow rate was achieved in 29 (43.28%) individuals in biosimilar arm and 14 (41.18%) individuals in the reference arm. The difference between the groups was statistically not significant (P = 0.8396). Four (5.71%) all-cause mortality were reported in biosimilar TNK arm compared to 2 (5.71%) in reference arm (all-cause mortality rate at 30 days' post dosing) and the difference between the two arms was statistically not significant (P = −1.00). Conclusion: Biosimilar TNK demonstrated biosimilar equivalence with the reference product in terms of the efficacy and safety analysis in this Phase III study and may be considered as a suitable alternative to reference TNK in patients with STEMI.

Currently, withdrawal and recall of medicines become a hot topic of discussion. This issue does not follow a uniform pattern all over the world. Few medicines continue to remain in the market despite reported adverse effects. This is understandable because: • They may be the only available options for a few sets of patients e.g. felbamate (anti-epileptic) • Drug remains in the market until better options are available in terms of safety and efficacy e.g. terfenadine approved in 1985 was found to cause cardiac arrhythmias but it continued to be in the market till the arrival of newer analogue fexofenadine in 1997. • Withdrawal may also become the last option to choose if all other risk management techniques fail as was observed in the case of heartburn treatment with cisapride

Background: Oxidative stress has emerged as an important factor in the pathophysiology of hypertension. It also contributes to various complications associated with hypertension like vascular injury, atherosclerosis, renal dysfunction, and hypertensive end-organ damage. Present study was done to evaluate the effect of atenolol and enalapril, two commonly prescribed antihypertensive drugs, on oxidative stress in patients with hypertension. Method: Sixty newly diagnosed hypertensive patients were randomly assigned to either atenolol (n = 30) or enalapril therapy (n = 30) and followed up for the period of three months. Twenty normotensive healthy volunteers served as control. Plasma malondialdehyde, superoxide dismutase and catalase levels were measured at the time of enrollment and at the end of three months of antihypertensive treatment. Results: Plasma malondialdehyde was significantly increased whereas superoxide dismutase and catalase were significantly reduced in newly diagnosed hypertensive patients compared to controls. After three months of enalapril therapy, plasma malondialdehyde was significantly reduced and superoxide dismutase and catalase were significantly elevated. Atenolol therapy had no effect on these oxidative stress parameters. Conclusions: Enalapril therapy significantly reduced oxidative stress in contrast to atenolol. Thus enalapril therapy may prove beneficial compared to atenolol by preventing oxidative stress and related complications in hypertension in view of life long therapy required for the treatment of hypertension.