Efficacy and safety of biosimilar romiplostim in Indian patients with chronic immune thrombocytopenia: A multicentric retrospective study.

Context and Aims: To evaluate the efficacy and safety of biosimilar romiplostim in Indian patients with immune thrombocytopenic purpura (ITP). Settings and Design: Multicentre, retrospective observational study. Methods and Material: Patients with chronic ITP who received biosimilar romiplostim from July 2019 to March 2020 across 3 major hospitals in Guwahati, India, were included. The study outcomes were the platelet response (platelet count > 50 × 109/L), time to first response, number of dose-limiting events, and the median effective dose. Statistical Analysis Used: Descriptive. Results: Of 32 patients included in this analysis, majority (59.4%) were females. The mean (SD) age was 40.37 (15.79) years, and mean age at ITP diagnosis was 38.53 years. The median number of romiplostim doses were 27.5 (range: 10-42) over a period of 10 months; median romiplostim dose used was 4.2 µg/kg (range: 2.8-5 µg/kg). Platelet response was achieved as early as after one week in 9 (28.12%) patients, which continued to increase to 24 (75%) patients after the second, 30 (93.75%) patients after the third and all 32 (100%) patients after four weeks of romiplostim administration. The median platelet count was 161 × 109/L. Dose reduction was done in a total of 21 patients. Thrombocytosis (46.88%), elevated liver enzymes (15.63%) and myalgia (15.63%) were the most common adverse events. Conclusions: Biosimilar romiplostim was effective in achieving and maintaining platelet response without any new safety concerns in Indian adult patients with chronic ITP. The median effective dose of romiplostim required in our patients was lower as compared with the standard prescribed dose.

Indigenous antithymocyte globulin-equine to treat aplastic anaemia in adults: a case series from two centres in northeast India.

BACKGROUND: Immunosuppressive therapy is the standard management of adults with aplastic anaemia. Antithymocyte globulin is used as first-line treatment of patients not eligible for bone marrow transplantation. This being a rare disease, available evidence in India is scarce. This study aimed to present experience in treating adult aplastic anaemia patients by immunosuppressive therapy using antithymocyte globulin-equine (Thymogam) in two tertiary care centres of northeast India. METHODS: This case series was conducted at the Health city hospital, Guwahati, and Excel Care Hospital, Guwahati from 2018 to 2020. Eighteen adult aplastic anaemia patients who were treated by immunosuppressive therapy with antithymocyte globulin-equine (Thymogam) and followed up for two years were included. Treatment response and relapse are described. RESULTS: All the 18 patients, (14 severe, four very severe) were uniformly treated with immunosuppressive therapy (Thymogam 40 mg/kg/d for four days with oral Cyclosporine from Day-1). Cyclosporin A was used as a concomitant drug in 94.44 % of the patients. At two years of follow up, 66.7 % showed a response and the mortality rate was 11.1 %. CONCLUSION: The results of this case series substantiate the effectiveness of immunosuppressive therapy with a low-cost preparation of horse antithymocyte globulin (Thymogam) along with cyclosporin A in the management of aplastic anaemia patients not suitable for bone marrow transplantation.

Solution pH jump during antibody and Fc-fusion protein thaw leads to increased aggregation.

Freeze-thaw cycles impact the amount of aggregation observed in antibodies and Fc-fusion proteins. Various formulation strategies are used to mitigate the amount of aggregation that occurs upon putting a protein solution through a freeze-thaw cycle. Additionally, low pH solutions cause native antibodies to unfold, which are prone to aggregate upon pH neutralization. There is great interest in the mechanism that causes therapeutic proteins to aggregate since aggregate species can cause unwanted immunogenicity in patients. Herein, an increase in aggregation is reported when the pH is adjusted from pH 3 up to a pH ranging from pH 4 to pH 7 during the thaw process of a frozen antibody solution. Raising the pH during the thaw process caused a significant increase in the percent aggregation observed. Two antibodies and one Fc-fusion protein were evaluated during the pH jump thaw process and similar effects were observed. The results provide a new tool to study the kinetics of therapeutic protein aggregation upon pH increase.

Analytical techniques for characterization of raw materials in cell culture media.

Raw materials are a critical part of any cell culture medium; therefore, it is of utmost importance to understand and characterize them for high-quality product. The raw material characterization (RMC) program at SAFC focuses on individual screening of raw materials both analytically and biologically. The goal of the program is to develop the best-in-class knowledge base of the raw materials used in SAFC's media formulations and their impact on performance of products.