Comparative evaluation of efficacy, pharmacodynamics, and safety of Hetero's adalimumab (Mabura®, Hetero Biopharma Ltd.) and reference adalimumab (Humira®, Abbvie Inc.) in patients with active rheumatoid arthritis on concomitant methotrexate therapy.

BACKGROUND: Our study aimed to compare efficacy and safety of Hetero's adalimumab (Mabura®, Hetero Biopharma Limited) versus reference adalimumab (Humira®, Abbvie Inc.) in Indian patients with active rheumatoid arthritis (RA) concomitant on methotrexate (MTX) therapy. METHODS: Patients (n = 168) were randomized (2:1) to receive either test or reference product for 24 weeks with concomitant MTX. Proportion of patients achieving American College of Rheumatology 20 (ACR20) criteria at week 12 was the primary endpoint. Changes in Disease Activity Score of 28 joints-C-reactive protein (DAS28-CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), and patients achieving ACR20 at week 24, ACR50/70 at weeks 12 and 24 were secondary endpoints. RESULTS: Patients achieving ACR20 responses with test (96.43%) were similar to reference (96.43%) in intention-to-treat (ITT) analysis at week 12. Proportional difference (PD) between groups (PD [95% CI] 0.0 [- 6.0, 6.0], p = 1.000) for ACR20 at week 12 for ITT analysis showed lower limit of the two-sided 95% CI was above the pre-specified noninferiority margin of - 15%. Similar trend in PP analysis (PD [95% CI] 0.0 [- 0.03, 0.07], p = 1.000), confirmed therapeutic equivalence. No significant difference was noted between arms for patients attaining ACR20 at week 24 and ACR50/70 at weeks 12 and 24 (all p > 0.05). DAS28-CRP and HAQ-DI were similar between groups. Total of 54 patients reported 88 AEs during the study. Out of these, 60 AEs were reported in 34 patients with Hetero-Adalimumab and 28 AEs were reported in 20 patients with Reference-Adalimumab. Total two patients, one in each group reported two serious adverse events (Sinusitis and Viral infection) during the study and resolved completely. No deaths and no life threatening AEs were reported. CONCLUSION: Results demonstrated Hetero's adalimumab is as effective and well tolerated as reference adalimumab in patients with active RA concomitantly on MTX therapy. TRIAL REGISTRATION: CTRI/2016/04/006884, Registered on 28/04/2016.

Correction to: Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase-III trial.

Following publication of the original article [1], the authors reported errors in the presentation of Tables 2, 4 and 5.

Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase-III trial.

BACKGROUND: Darbepoetin alfa (DA-α) is a long-acting erythropoiesis-stimulating glycoprotein which has half-life three-fold longer than that of Erythropoietin alfa (EPO). The objective of this study was to compare the efficacy and safety of DA-α injection versus EPO for treating renal anemia amongst Indian patients with end-stage renal disease (ESRD) undergoing dialysis. METHODS: Patients of either gender (aged 18-65 years) with ESRD undergoing dialysis who had hemoglobin (Hb) levels < 10 g/dL after receiving EPO were switched to DA-α (0.45 µg/kg) once weekly subcutaneously or EPO 50 IU/kg thrice weekly subcutaneously (centrally randomized 1:1) for 12-24 weeks (correction phase) followed by 12 weeks maintenance phase (for Hb levels ≥10 g/dL). The primary efficacy endpoint was mean change in Hb level from baseline to end of correction phase. RESULTS: In the intention-to-treat population (n = 126), the between group difference in mean Hb change was - 0.01 g/dL (95% CI - 0.68 to - 0.66, p = 0.97). After adjusting for covariates, the difference was - 0.2878 g/dL (95% CI -0.936 to0.360). The lower limit of the two-sided 95% CI of primary endpoint was above the pre-specified non-inferiority margin of - 1.0 g/dL. Similar trend of non-inferiority was observed for per-protocol population. Safety profile of DA-α and EPO were observed to be similar. CONCLUSION: Our study results demonstrated that for patients with ESRD undergoing dialysis, administering DA-α at lower dose frequency, is equally effective and well tolerated as EPO for treating renal anemia. TRIAL REGISTRATION: CTRI/2012/07/002835 [Registered on: 27/07/2012]; Trial Registered Prospectively.

A Prospective, Randomized, Multiple-Dose, Multi-Center, Comparative Clinical Study to Evaluate the Efficacy, Safety, Immunogenicity of a biosimilar Bevacizumab (Test product, Hetero) and Reference Medicinal Product (Bevacizumab, Roche) in Patients of Metastatic Colorectal Cancer.

OBJECTIVE: :To compare efficacy and safety of a biosimilar, Bevacizumab (Hetero) vs reference medicinal product (Bevacizumab, Roche) as first line therapy in patients with metastatic colorectal cancer (mCRC) in combination with chemotherapy. METHODS: Patients of aged 18 to 65 with histologically pre-confirmed mCRC and treatment naïve with unresectable metastatic disease or distant metastases were enrolled and randomized to receive either Hetero-Bevacizumab or RMPBevacizumab along with chemotherapy (XELOX or FOLFOX-4) regimen over a period of 24 weeks (up to 8 cycles of Hetero-Bevacizumab/RMP-Bevacizumab+ XELOX regimen (each cycle of 3 weeks) or up to 12 cycles of Hetero-Bevacizumab/ RMP-Bevacizumab + FOLFOX-4 regimen (each cycle of 2 weeks). Bevacizumab was administered at 7.5 mg/kg as an IV infusion over 60-90 minutes on Day 1 of each treatment cycle. The efficacy endpoints were the overall response rate (CR+PR) and disease control rate (DCR) according to RECIST 1.1. The safety endpoints included assessments of treatment emergent adverse events and immunogenicity. RESULTS: 160 patients were screened; 111 patients were randomized in the study. No statistical significant difference in overall response rate between both the treatment groups (HB-MAB vs. RB-MAB: 35.56 % vs. 20%, P=0.28 at Week 6; 37.50 % vs. 30.77 %, P=0.73 at Week 12). Similar trend was observed for disease control rate (HB-MAB vs. RB-MAB: 100% vs. 96%, P=0.36 at Week 6; 95.83 vs. 100%, P=1.00 at Week 12). CONCLUSIONS: Herero's Bevacizumab was found to be comparable to reference medical product, Bevacizumab in terms of efficacy and tolerability for the Indian patients with metastatic colorectal cancer.

Efficacy, Safety and Immunogenecitystudy of Intravenous Infusion of Rituximab (Hetero) and Reference Medicinal Product (Rituximab, Roche) in Indian Patients of Follicular Lymphoma Preliminary report (HERILY).

OBJECTIVE: To compare the antitumor efficacy, safety, and pharmacodynamics (PD) characteristics of Hetero-Rituximab (test) with Reference Medicinal Product (Rituximab, Roche) in Non-Hodgkin's Lymphoma (NHL). PATIENTS AND METHODS: Total 40 Follicular Lymphoma (FL) patients were randomized to receive intravenous infusion of either test or reference product. Efficacy (best overall response [BOR] rate [primary end point]), safety, PD (CD19), and immunological assessments (secondary end points) were done at the end of cycle 3 and cycle 6. RESULTS: Out of 40 patients randomized, 17 were in test arm while 23 were in reference arm. At the end of 6 cycles, BOR (complete response [CR] and partial response [PR]) rate was 64.71% (n=11) in Hetero Rituximab compared to the 43.48% (n=10) in reference arm. The difference between test and reference proportions of best overall response rate at cycle 6, lies within the pre-specified limit for noninferiority. Anti-Rituximab antibodies were found to be negative at cycle 3 and cycle 6 for all FL patients. The FL patients who were treated with Hetero Rituximab, showed significant depletion in CD19+ cell which was comparable with Reference drug. Safety and Immunogenic potential of the test drug was comparable to the reference drug in the patients of FL. CONCLUSION: Best overall response rate at Cycle 3, Cycle 6 and end of the study lies within the pre-specified limit for non-inferiority which concludes that test product is therapeutically non-inferior to reference medicinal product.