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Findings from the phase 1 study informed the clinical development program for GP40141 as a biosimilar treatment for ITP, demonstrating pharmacodynamic similarity to reference romiplostim.
Results from a phase 1 study revealed comparable pharmacodynamic profiles between GP40141 and romiplostim, providing clinical pharmacology evidence for GP40141 as a biosimilar candidate to romiplostim for idiopathic thrombocytopenic purpura (ITP).
The randomized, double-blind, single-dose, crossover comparative adaptive study was billed as the first of its kind to fully describe the pharmacokinetic profile of romiplostim in healthy male volunteers at a clinically relevant and safe dose after subcutaneous administration, with results informing the clinical development of the GP40141 biosimilar for ITP.1
“The aim of developing the romiplostim biosimilar GP40141 is to reduce the cost of the drug and therefore make the treatment more affordable among patients with ITP,” wrote investigators.1
A blood disorder characterized by an abnormal decrease in the number of platelets in the blood, ITP causes easy bruising, bleeding gums, and internal bleeding.2 Romiplostim was approved for the treatment of ITP by the US Food and Drug Administration in 2008. It works by stimulating the bone marrow to produce more platelets.3 Developing a biosimilar for romiplostim can reduce the financial burden and address barriers to treatment for patients with ITP by lowering healthcare-related costs.
To compare pharmacodynamics, pharmacokinetics, and safety between GP40141 and reference romiplostim, Igor Makarenko, MD, PhD, head of clinical trials at GEROPHARM, and colleagues randomly assigned healthy Caucasian male patients to receive both treatments during 2 periods lasting 33 days. Eligible participants were aged 18-45 years with a total body weight between 60-100 kg, a body mass index between 18.5-30 kg/m2, a platelet count between 150.0–306.0 × 109/L, and good general health, determined by no clinically significant findings from their medical history, physical examination, 12-lead electrocardiogram, vital sign measurements, and clinical laboratory evaluation.1
In total, 56 participants were enrolled in the study. All patients in the cohort were male and had a mean age of 29.54 (Standard deviation [SD], 4.56) years, mean body weight of 78.5 (SD, 11.0) kg, and mean body mass index of 24.7 (SD, 2.7) kg/m2. After a 14-day screening period, investigators randomized participants in a 1:1 ratio to receive a 3 ug × kg−1 subcutaneous dose of GP40141 and reference romiplostim during 33-day treatment periods.1
Patients in the first group (n = 28) received GP40141 during the first period and reference romiplostim during the second period, while patients in the second group (n = 28) received reference romiplostim in the first period and GP40141 in the second period. Between the administration of GP40141 or reference romiplostim on the first day of each treatment period, there was a 33-day washout period during which no treatment was given.1
Investigators established 2 primary outcomes of interest to determine the pharmacodynamic similarity between GP40141 and reference romiplostim. The first was the area under the platelet count curve (AUCplt) from time 0, calculated as the mean of the platelet counts obtained at 45, 30, and 15 minutes before the treatment, to the time of the last sampling for pharmacodynamics. The second primary endpoint was the maximum observed platelet count (Pmax). Secondary outcomes included the maximum number of platelets count to the basal level of platelets (Pmax/P0), the time to reach the maximum number of platelets count (tPmax), and pharmacokinetic measures.1
Upon analysis, the 90% confidence interval for the geometric mean ratios for AUCplt and Pmax were fully contained within the predefined equivalence limits of 80%–125%. The mean AUCplt was 253366.65 (109/L × h) for GP40141 and 252053.01 (109/L × h) for the reference formulation, and the mean Pmax was 559.78 (109/L) for GP40141 and 546.27 (109/L) for the reference romiplostim. Investigators pointed out the mean time to tPmax was approximately 283.71–292.29 h across both treatments. The mean pharmacokinetic parameters for the AUC from time 0 to the time of the last observable concentration were 3181.84 (pg/mL × h) for GP40141 and 2763.17 (pg/mL × h) for the reference romiplostim. The maximum observed serum concentration was 43.75 (pg/mL) and 40.06 (pg/mL) for GP40141 and romiplostim, respectively.1
Investigators noted no adverse events were observed in relation to GP40141 or the reference romiplostim. According to the results of a complete blood count test and biochemical profile, there were no clinically relevant deviations among the cohort. Urinalysis, assessment of the vital signs, physical examination, and evaluation of injection site tolerability also showed no deviations.1
“The results from the present study provide evidence to support the similarity between GP40141 and the reference romiplostim and contribute to obtaining complete evidence for biosimilarity in a phase III confirmatory trial as required by international guidelines,” concluded investigators.1