akr-501 and fostamatinib

In this review, the recently approved drugs avatrombopag and fostamatinib, which were not extensively covered within 2019 international recommendations for ITP, will be discussed in some detail. Avatrombopag appears more convenient than eltrombopag as it does not require dietary restrictions or subcutaneous administration like romiplostim. However, data on quality of life (QoL) are lacking and the rate of thromboembolic events in exposed patients is not negligible. Efficacy of fostamatinib, an inhibitor of macrophagic activity, is supported by placebo-controlled trials in patients refractory to several therapies, including TPO-RA. While hypertension and diarrhea have been reported, only one minor thrombotic event occurred in 146 exposed patients. In addition, several new treatment combinations and new agents entered clinical investigation in recent years. In a UK trial, combining mycophenolate mofetil with corticosteroids as first line therapy was more effective than corticosteroids alone, but at the cost of worse QoL. No combination, including oseltamivir or all-trans retinoic acid or danazol, resulted in convincing evidence of superior efficacy and safety when used in first or later lines of treatment. Agents targeting specific mechanisms are also discussed: sutimlimab (complement inhibitor); rilzabrutinib (BTK inhibitor) and efgartigimod (modified Fc fragment inhibiting FcRn). Only efgartigimod has completed phase 3 investigation.

Topics: Clinical Trials as Topic; Humans; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Receptors, Fc; Recombinant Fusion Proteins; Thiazoles; Thrombopoietin

Immune thrombocytopenia is a haematological, autoimmune disorder characterized by elevated platelet demolition due to the presence of antiplatelet autoantibodies derived from B cells and to an irregular, deficient process of platelets production in bone marrow. In this review, after a brief presentation of 'old' strategies used nowadays yet, we focused on new drugs used in the treatment of immune thrombocytopenia and their mechanism of action and posology, basing on the last scientific literature. The observation that CoViD-19 can be associated with immune thrombocytopenia is also put in evidence. Particular attention will be dedicated on the concept that the ideal treatment should represent a solution not only for the failure of normal processes of production and survival of platelets, but also it should improve quality of life of patients, with minimum adverse events. Anyway, despite enormous advances of the last years, further investigations are necessary in order to define scrupulously long-term efficacy of new molecules proposed.

Topics: Aminopyridines; Antibodies, Monoclonal, Humanized; COVID-19; Histocompatibility Antigens Class I; Humans; Immunosuppressive Agents; Morpholines; Protein Kinase Inhibitors; Purpura, Thrombocytopenic, Idiopathic; Pyrimidines; Receptors, Fc; Receptors, Thrombopoietin; SARS-CoV-2; Syk Kinase; Thiazoles; Thiophenes

This review provides details about three small molecules that were recently approved by the FDA for the treatment of thrombocytopenia. The new treatments include lusutrombopag, avatrombopag, and fostamatinib. The first two drugs are orally active thrombopoietin receptor (TPO-R) agonists which are FDA-approved for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. Fostamatinib is orally active prodrug that, after activation, becomes spleen tyrosine kinase (SYK) inhibitor. Fostamatinib is currently used to treat chronic and refractory immune thrombocytopenia in patients who have had insufficient response to previous treatment. Chemical structures, available dosage forms, recommended dosing, pharmacokinetics, results of toxicity studies in animals, most frequent adverse effects, significant outcomes of the corresponding clinical trials, and their use in specific patient populations are thoroughly described. Described also is a comparative summary of the different aspects of five currently available therapies targeting TPO-R or SYK for the treatment of thrombocytopenia.

Topics: Aminopyridines; Animals; Cinnamates; Drug Development; Humans; Morpholines; Oxazines; Pyridines; Pyrimidines; Receptors, Thrombopoietin; Small Molecule Libraries; Syk Kinase; Thiazoles; Thiophenes; Thrombocytopenia

This article reviews nine drugs recently approved by the FDA, including indications, precautions, adverse reactions, and nursing considerations.

Topics: Aminopyridines; Cinnamates; Drug Approval; Factor Xa; Humans; Macrolides; Morpholines; Oligonucleotides; Oxazines; Pyridines; Pyrimidines; Recombinant Proteins; RNA, Small Interfering; Sisomicin; Tetracyclines; Thiazoles; Thiophenes; United States; United States Food and Drug Administration