Pharmacokinetic Profiles of a Proposed Biosimilar Ustekinumab (BFI-751): Results From a Randomized Phase 1 Trial.

BioFactura has developed a proposed biosimilar candidate (BFI-751) to ustekinumab reference product. Results are reported for the first-in-human trial designed to compare the pharmacokinetic profiles, safety, and immunogenicity of BFI-751 and ustekinumab reference products from the European Union and United States as well as similarity of the EU and US reference products. This was a multicenter, randomized, double blind, 3-parallel-group study (trial ID: NCT04843631). Healthy subjects were randomized to receive a single subcutaneous dose of 45 mg of BFI-751, EU ustekinumab, or US ustekinumab. The pharmacokinetic parameters were area under the concentration-time curve (AUC) from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum concentration. Safety, tolerability, and immunogenicity data were also reported. Pairwise comparisons among the 3 treatments all met the standard bioequivalence criteria that the 90% confidence interval of the geometric mean ratios of AUC from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum concentration are completely within the acceptance interval of 80%-125%. There were no marked differences in the safety and tolerability profiles for subjects receiving BFI-751 as compared to EU or US ustekinumab. Treatment-emergent adverse events were mild to moderate for all treatment groups.

Iraqi regulatory authority current system and experience with biosimilars.

Biological medicines have significantly altered treatment for many patients with chronic diseases such as cancers, autoimmune diseases, and diabetes. However, the high cost of biological medicines has limited patients' access to them. Iraq is one of the countries that have decided to increase access to these medicines through biosimilars, which are copies of originator biological medicines. Prior to 2019, the Iraqi National Regulatory Authority (NRA) had no clear guidelines in place for biosimilars uptake. Therefore, approvals of many biosimilars were delayed. As a response to that, a new pivotal committee was found within this authority, and the first version of Iraqi basis and guidelines for the approval of biosimilars was enacted. With the implementation of the Iraqi biosimilars guidelines and escalating the cooperation within the Iraqi NRA, many benefits have been attained in a short time including the approval of many essential biosimilar products which has resulted in a total cost savings estimated to exceed 50 million USD in just the year 2020. However, there are still some barriers towards making the utmost benefit from biosimilars in Iraq, such as lack of familiarity of these products among the Iraqi health care providers which requires appropriate biosimilars-awareness enhancement strategies.

Biosimilars: where we were and where we are.

Recent progress in biosimilars development is overviewed, with attention to the history of issues and processes leading to current regulations, and to scientific considerations, including progress on design and operational implementation issues that arise and are peculiar to biosimilars trial design and implementation.

A phase III randomized equivalence study of biosimilar filgrastim versus Amgen filgrastim in patients receiving myelosuppressive chemotherapy for breast cancer.

BACKGROUND: Filgrastim was developed to treat chemotherapy-induced neutropenia. This phase III study was designed to demonstrate bioequivalence of Amgen filgrastim and a biosimilar filgrastim developed by Hospira (Study GCF071; sponsored by Hospira). PATIENTS AND METHODS: Breast cancer patients suitable for treatment with doxorubicin and docetaxel in the neoadjuvant/adjuvant or first-line metastatic setting were enrolled at 37 European centers. Patients were randomized (2:1) to receive Hospira filgrastim or Amgen filgrastim, after the end of chemotherapy. Filgrastim (5 µg/kg/day) was administered under double-blind conditions. Primary endpoint to demonstrate bioequivalence was duration of severe neutropenia (DSN) in cycle 1. RESULTS: 184 patients were randomized to Hospira filgrastim and 95 to Amgen filgrastim. Mean DSN in cycle 1 was similar with Hospira filgrastim (1.6 days; n = 165) and Amgen filgrastim (1.3 days; n = 85), meeting predefined criteria for bioequivalence. Secondary endpoints supporting bioequivalence included mean time to absolute neutrophil count recovery and incidence of febrile neutropenia. The most common treatment-related adverse event with Hospira filgrastim was grade 1-2 bone pain. CONCLUSIONS: Hospira filgrastim and Amgen filgrastim are bioequivalent in efficacy with similar safety profiles. Hospira filgrastim may be useful for the prophylaxis of complications related to neutropenia caused by chemotherapy.

Comparison of the pharmacodynamic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial.

Further to the patent expiry of Neupogen (Amgen filgrastim), Hospira has developed a biosimilar filgrastim (Nivestim) that may offer a clinically effective alternative for multiple hematologic and oncologic indications. Here results are reported from a phase I trial, primarily designed to compare the pharmacodynamic profiles of Hospira filgrastim and Amgen filgrastim. A phase I, single-center, double-blind, randomized trial was undertaken to demonstrate equivalence of the pharmacodynamic characteristics of Hospira filgrastim and Amgen filgrastim. Fifty healthy volunteers were randomized to receive 5 or 10 microg/kg dosing, before further randomization to treatment sequence. All volunteers received five daily subcutaneous doses of Hospira filgrastim or Neupogen, with subsequent crossover to the alternative treatment. Bioequivalence was evaluated by analysis of variance; if the estimated 90% confidence intervals (CIs) for the ratio of 'test' to 'reference' treatment means were within the conventional equivalence limits of 0.80-1.25, then bioequivalence was concluded. Forty-eight volunteers completed the study. Geometric mean absolute neutrophil count area under the curve from time 0 to the last time point at day 5 (primary endpoint) was comparable in volunteers given Hospira filgrastim or Amgen filgrastim at 5 microg/kg (ratio of means, 0.98; 90% CI, 0.92-1.05) or 10 microg/kg (ratio, 0.97; 90% CI, 0.93-1.01); 90% CIs were within the predefined range necessary to demonstrate bioequivalence. Hospira filgrastim was well tolerated with no additional safety concerns over Amgen filgrastim. Hospira filgrastim is bioequivalent with Amgen filgrastim with regard to its pharmacodynamic characteristics.

Pharmacokinetic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial.

Recombinant human granulocyte colony-stimulating factor (filgrastim) has multiple hematologic and oncologic indications as Neupogen (Amgen filgrastim). Hospira has developed a biosimilar filgrastim (Nivestim). Here, results are reported from a phase I trial, primarily designed to compare the pharmacokinetic profiles of Hospira filgrastim and Amgen filgrastim. A phase I, single-center, open-label, randomized trial was undertaken to demonstrate equivalence of the pharmacokinetic characteristics of Hospira filgrastim and Amgen filgrastim. Forty-eight healthy volunteers were randomized to receive intravenous (i.v.) or subcutaneous (s.c.) dosing and then further randomized to order of treatment. Volunteers in each of the two dosing groups received a single 10microg/kg dose of Hospira filgrastim or Amgen filgrastim, with subsequent crossover. Bioequivalence was evaluated by analysis of variance; if the estimated 90% confidence intervals (CIs) for the ratio of 'test' to 'reference' treatment means were within the conventional equivalence limits of 0.80-1.25, then bioequivalence was concluded. Forty-six volunteers completed the study. Geometric mean area under the curve from time 0 to the last time point (primary endpoint) was similar in volunteers given Hospira filgrastim or Amgen filgrastim following i.v. (ratio of means: 0.96; 90% CI: 0.90-1.02) or s.c. (ratio of means: 1.02; 90% CI: 0.95-1.09) dosing; 90% CIs were within the predefined range necessary to demonstrate bioequivalence. Hospira filgrastim was well tolerated with no additional safety concerns over Amgen filgrastim. Hospira filgrastim is bioequivalent with Amgen filgrastim in terms of its pharmacokinetic properties and may provide a clinically effective alternative.