China
Africa
Explore chapters and articles related to this topic
Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Daniel Bobo, Kye J. Robinson, Jiaul Islam, Kristofer J. Thurecht, Simon R. Corrie
The most basic class of polymeric nanomedicines is utilization of single polymer chains either directly as the therapeutic, or as a modifying agent for a drug or diagnostic agent. As direct drugs, there are a number of examples of both FDA-approved products and those under clinical trial. The best example is Copaxone® (glatiramer acetate), which is a random copolymer composed of L-glutamic acid, L-alanine, L-lysine and L-tyrosine [31]. Initially approved in 1996, Copaxone® was a revolutionary treatment that acted as an immunomodulator in the treatment of multiple sclerosis. More frequently in terms of polymeric nanomedicines, drugs are attached to a hydrophilic polymer to increase circulation or improve biocompatibility/solubility [32]. The most well-established polymer is poly (ethylene glycol) (PEG). Such systems include the extremely popular and successful drug Neulasta® (PEGylated granulocyte colony stimulating factor), which has been FDA-approved since 2002 for chemotherapy-induced neutropenia. In this case, PEGylation resulted in a significant increase in biological half-life in plasma (15–80 h compared to only 3–4 for the basic filgrastim [33]). More recently, the FDA has approved 2 new PEGylated biologic drugs. In 2014, PEGylated interferon gamma beta-1a (PEGylated IFN beta-1a; PLEGRIDY®) was approved for treatment of relapsing multiple sclerosis. Addition of PEG to the therapeutic protein improved biological half-life and exposure in comparison to the protein alone [34]. In comparison to Copaxone® and other IFN-based MS treatments which are often administered daily, PLEGRIDY® can be administered every 2–4 weeks. In 2015, PEGylated antihemophilic factor VIII (ADYNOVATE) was approved for treatment of hemophilia A, both in terms of preventing bleeding episodes, or treating acute bleeding. Based on the increased half-life of this drug in comparison to non-PEGylated factor VIII, there is also hope that the need for less frequent administration may reduce the incidence of antifactor VIII antibody generation, which affects up to 30% of patients (for most biologics, antidrug antibody generation occurs in <5% of patients) and leads to reduced drug efficacy [35]. There are also a large number of polymer-immobilized nanomedicines that are under Phase II or III investigation in clinical trials. By way of example, NKTR-102 is a PEGylated etirinotecan drug, that has extended into Phase III clinical trials [36]. The trial showed that extended exposure of tumor cells to the topoisomerase-I inhibitor typically showed enhanced therapeutic response – this is attributed to the longer circulation of PEGylated nanomaterials. In addition to PEGylation, other hydrophiles can be utilized to increase circulation. A polymer-drug conjugate of paclitaxel and polyglutamic acid (poliglumex (PPX)) has entered phase III trials and is showing significantly improved standard of living for patients who undergo paclitaxel therapy for non-small cell lung cancer [37]. This exemplifies the fact that while PEGylated polymers have been most extensively utilized in nanomedicine, other examples of hydrophiles can be equally successful in improving therapeutic outcomes.
Insights into human factor studies conducted for US FDA-approved biological combination products
Published in Expert Opinion on Drug Delivery, 2019
Ronak Patel, Miten Mehta, Parag Pipalava, Meghana Dahiya, Inderjeet Singh, Vinu Jose
The PFS is a commonly used device for many drug products across various disease conditions, and patients, caregivers, and HCP are expected to be aware of its usability. The US FDA guidance also states that the HF validation study is not required for the PFS with commonly and well-understood design. However, HF studies were conducted with 18/24 (75%) PFS devices included in this article. Reasons for conducting HF studies with PFS devices may be the following: (i) the drug product and device being new for the disease condition (e.g. Aimovig, Ajovy, Dupixent®, Praluent, Repatha), (ii) the drug product being used in patients with neuromuscular disease (e.g. Plegridy, Zinbryta®), (iii) the drug product being used in patients with limited dexterity (e.g. Amjevita, Cyltezo®, Kevzara®), (iv) some modifications being introduced to the PFS device to differentiate it from other similar devices, and (v) comfort factor of organization.
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
Interferon beta-1a (IFNβ-1a) and interferon beta-1b (IFNβ-1b) are first-line drugs in the treatment of RRMS. Particularly, IFNβ-1b (Betaferon®, approved in 1993 by FDA and in 1995 by EMA) is also indicated for the treatment of ‘active’ SPMS according to EAN guidelines [6]. It is administered through subcutaneous injection (s.c.) every other day at a dose of 250 µg, with a half-life up to 4.3 h. IFNβ-1a can be administered intramuscularly (i.m.) at a dose of 30 µg once a week (Avonex®, approved in 1996 by FDA and EMA) or s.c. at two different dosages, 22 and 44 µg three times a week (Rebif®, approved in 1998 by EMA and in 2002 by FDA). Recently a pegylated IFNβ-1a (Plegridy®, approved in 2014 by FDA and EMA) has been introduced, needing only one s.c. administration every 2 weeks due to a longer half-life [7].
Recent developments in interferon-based therapies for multiple sclerosis
Published in Expert Opinion on Biological Therapy, 2018
Laura Dumitrescu, Cris S. Constantinescu, Radu Tanasescu
Currently, five self-injectable pharmaceutical formulations are available: subcutaneous IFN-β-1b 250 µg, every other day (Betaferon®/Betaseron®, approved in 1993; generic, e.g. Extavia®, also available), intramuscular IFN-β-1a 30 µg, weekly (Avonex®, approved in 1996), subcutaneous IFN-β-1a 44 or 22 µg, thrice weekly (Rebif®, approved in 2002), and subcutaneous PEGylated IFN-β-1a (PEG-IFNb1a) 125 µg every two weeks (Plegridy®, approved in 2014) [3,40–43]. All these are recombinant humanized IFN-β molecules, and except for PEG-IFN-β-1a have relatively low half-life. The biological activity differs between formulations and may be measured in vitro by using the vesicular stomatitis virus cytopathic effect assay [44]. Besides IFN-β-1b, which is produced in Escherichia coli, all other formulations are produced in Chinese hamster ovary cells and are thus glycosylated [3,41–43].