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Statistical Methods for Assessment of Complex Generic Drugs
Published in Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow, Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
Glatiramer acetate is a complex mixture of synthetic polypeptides, which is a representative of drugs with complex APIs. In the PSG of glatiramer acetate, a four-stage criterion is recommended for the demonstration of API sameness (Bell et al., 2017; US FDA, 2018c): (i) equivalence of fundamental reaction scheme; (ii) equivalence of physicochemical properties including compositions; (iii) equivalence of structural signatures for polymerization and depolymerization; and (iv) equivalence of biological assay results. A biological assay can serve as a confirmatory test of equivalence and provide complementary confirmation of API sameness. As the formulation of glatiramer acetate relatively simple (parenteral solution), if the generic product is qualitatively (Q1) and quantitatively (Q2) the same in terms of API and inactive ingredients as the reference product, the requirement of in vivo BE study could be waived (US FDA, 2018c).
Therapeutic Gases for Neurological Disorders
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
R. Rachana, Tanya Gupta, Saumya Yadav, Manisha Singh
Multiple sclerosis currently is an inoperable and fatal disorder. Attempts to cure it are limited to treatments such as plasmapheresis and corticosteroids administration, etc., which results in similar effects like modification of disease succession and declining in degeneration rate by HBOT (Bennett et al., 2004). Majority of such measures include immunosuppressive or immunomodulatory agents. Drugs including interferon-β (IFN-β), glatiramer acetate (GA), intravenous immunoglobulin, mitoxantrone, methotrexate, and corticosteroids are used for the treatment of multiple sclerosis (Goodin et al., 2002).
Organ-specific autoimmune diseases
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, George C. Tsokos
Two mechanisms of action have been proposed for glatiramer acetate. One is that this compound is a TCR antagonist of the immunodominant 82–100 epitope of MBP, thus turning off the immune response to MBP. The other is that glatiramer acetate administration may lead to a tolerant state by downregulating T-cell immune responses to MBP. This effect is supposed to be mediated by IL-10–secreting Treg lymphocytes.
An update on the safety of treating relapsing-remitting multiple sclerosis
Published in Expert Opinion on Drug Safety, 2019
Clara G. Chisari, Simona Toscano, Emanuele D’Amico, Salvatore Lo Fermo, Aurora Zanghì, Sebastiano Arena, Mario Zappia, Francesco Patti
GA has the lowest pregnancy risk among all the DMDs in MS. EAN guidelines do not avoid the use of glatiramer during pregnancy [6] and the drug does not require discontinuation until conception in women who are planning a pregnancy. More recently, the previous pregnancy contraindication has been removed from the label of Copaxone 20 mg/ml by the Medicines and Healthcare Products Regulatory Agency in the UK, with the agreement of all concerned European Union member states [64]. Indeed, information about more than 7,000 pregnancies have been collected over more than 20 years in Teva’s Glatiramer Acetate Pharmacovigilance Database and no higher risk for teratogenic effects has been assessed in pregnancies exposed to GA [65], confirming the outcomes of previous smaller reports [66]. No data are available about breastfeeding, even if GA is considered as probably compatible with lactation. Indeed, crossing into breast milk is unlikely, due to its large molecular weight and potential low oral availability in infant [67] (Tables 1 and 2).
Implications of immunotherapy with high-dose glatiramer acetate in acute phase of spinal cord injury in rats
Published in Immunopharmacology and Immunotoxicology, 2019
Hadi Askarifirouzjaei, Leila Khajoueinejad, Amir Salek Farrokhi, Mohammad-Taher Tahoori, Mehdi Fazeli, Taki Tiraihi, Ali Akbar Pourfathollah
A previous study reported the effectiveness of oral feeding of Glatiramer acetate in suppressing EAE in rats [32]; whereas five times feeding was performed before disease induction and EAE was induced two days after the last feeding. In addition, it has been demonstrated that Glatiramer acetate treatment significantly decreases motor neuron death after facial nerve axotomy if Glatiramer acetate is injected to animals seven days before nerve injury [13]. It has also been reported that functional recovery is impaired after high-dose immunization with MBP-derived altered peptide ligands following spinal cord injury, whereas low-dose treatment group shows improved BBB scores [33]. Furthermore, high-dose Glatiramer acetate (3.5 mg/kg) in acute ischemic stroke in mice did not reduce lesion volumes and had no significant effect on functional recovery outcome [34]. In addition, systematic review showed that Glatiramer acetate had no significant effect on advancement of disease in progressive form of multiple sclerosis compared with relapsing remitting (RR) form of disease [35]. Thus, our results are in line with those of previous studies indicating that Glatiramer acetate administration following SCI appears to be dependent upon dose and time of administration.
First-line disease-modifying drugs in relapsing–remitting multiple sclerosis: an Italian real-life multicenter study on persistence
Published in Current Medical Research and Opinion, 2018
Diana Ferraro, Valentina Camera, Eleonora Baldi, Veria Vacchiano, Erica Curti, Angelica Guareschi, Susanna Malagù, Sara Montepietra, Silvia Strumia, Mario Santangelo, Luisa Caniatti, Matteo Foschi, Alessandra Lugaresi, Franco Granella, Ilaria Pesci, Luisa Motti, Walter Neri, Paolo Immovilli, Enrico Montanari, Francesca Vitetta, Anna Maria Simone, Patrizia Sola
In this prospective, multi-center, real-life observational study, participating centers enrolled RRMS patients commencing any of the following first-line DMDs: interferon beta 1a/1b, pegylated interferon, glatiramer acetate, dimethylfumarate and teriflunomide. Patients aged <18 years and unwilling/unable to provide informed consent were excluded from the study. A switch from glatiramer acetate 20 mg a day to 40 mg three times a week or from interferon beta 1a/1b to pegylated interferon, for convenience reasons only, was not considered a discontinuation, and patients were only included if either the new formulation was discontinued due to tolerability/efficacy issues or if they had completed a 12 month observation period, without discontinuing, on one or the other drug formulation. Patients gave written consent to the inclusion in the study, which was approved by the Ethics Committee of the coordinating center (nr. 189/15) and by the Ethics Committees of the participating centers.