Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Jun 2014
ReviewPreterm labour: association between labour physiology, tocolysis and prevention.
In developed countries, preterm birth is the major cause of perinatal morbidity, mortality and the most important public health problem in the obstetric field. In the past decades, an increasing trend has been observed regardless of the great efforts focussed on the improvement of our understanding of the physiopathological mechanisms behind preterm labour (PTL) and the improvement in the use of tocolytic drugs. ⋯ There is a need to develop new tools for the treatment of patients with PTL. Research focussed on improving tocolysis, the physiology of labour and pathological processes involved in PTL would afford new approaches for the treatment of PTL, allowing clinicians to provide integrative solutions for this multifactorial disease. Recently, the prophylactic use of progesterone pessary and cerclage in women with high risk of premature labour has been reported to reduce the incidence of premature births and improve neonatal outcomes. These results highlight the importance of prediction models in order to establish preventative strategies early in pregnancy.
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Expert Opin Investig Drugs · Jun 2014
ReviewDesmoteplase as a potential treatment for cerebral ischaemia.
Desmoteplase is an investigational plasminogen activator found in the saliva of the vampire bat, Desmodus rotundus. It has been of scientific interest for over 25 years as it exhibits pharmacological properties that have led to the hypothesis that desmoteplase may be safer and more effective than recombinant tissue plasminogen activator (rtPA) in arterial thromboembolic disease, and in particular, acute ischaemic stroke (AIS). ⋯ In contrast to rtPA, and despite a similar structure, desmoteplase has demonstrated high selectivity for fibrin and an absence of neurotoxicity in experimental models. Demonstrating such properties in animal models, one would have expected an ambitious clinical study future. Phase II and Phase III clinical studies in patients with AIS demonstrated an excellent safety profile with low risk of symptomatic intracranial haemorrhage compared to rtPA. However, data on clinical and radiological efficacy end points of desmoteplase in AIS are inconclusive. Further Phase III trials are currently underway and their results are eagerly awaited.
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Expert Opin Investig Drugs · Jun 2014
ReviewInvestigational approaches to therapies for restless legs syndrome.
Restless Legs Syndrome (RLS) is a common neurological disorder that impairs nocturnal rest, causing decreased alertness, depressed mood, reduced job performance and poor quality of life. In patients affected by severe RLS, pharmacological treatment is mandatory. ⋯ The drugs currently available for treating RLS do not always allow the patient to obtain a dose capable of controlling the symptoms, particularly in the long term. There is still the need for effective and well-tolerated new drugs. Monoamine oxidase B inhibitors could be good candidates for the initial treatment of RLS, sparing stronger dopaminergic agents for later stages of the disease. Oxycodone-naloxone has demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled with first-line drugs; it could be used as a long-term treatment option in severe cases of RLS for which alternative satisfactory drug regimens are unavailable. There is a paucity of data comparing medications in head-to-head trials to determine their relative effectiveness and adverse event profiles. Furthermore, there is also a need for further studies that evaluate nondopaminergic agonists and combination therapies for treating RLS.
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Expert Opin Investig Drugs · Apr 2014
ReviewARA 290 for treatment of small fiber neuropathy in sarcoidosis.
Painful peripheral neuropathy is a common, difficult-to-treat complication associated with a variety of diseases, including diabetes mellitus and sarcoidosis. It is caused by damage of small and autonomic nerve fibers, resulting in potentially debilitating symptoms of neuropathic pain and autonomic dysfunction. The limited efficacy of current treatment options dictates a rationalized design of novel compounds. ⋯ Current treatment modalities of neuropathy are based on a trial-and-error approach, have limited efficacy and come with significant side effects. Given the excellent safety profile while reducing neuropathy symptoms, the prospects of ARA 290 treatment in sarcoid neuropathy seem promising. The long-lasting beneficial effects of ARA 290 on both pain-related and non-pain-related symptoms in sarcoidosis patients prompt additional studies on potential disease-modifying properties of ARA 290.
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Multiple myeloma (MM) remains incurable despite important recent advances in treatment due to its inherent resistance, characterized by highly complex and heterogeneous molecular abnormalities, as well as the support from myeloma bone marrow (BM) microenvironment. A novel therapeutic strategy that effectively targets specific molecules on myeloma cells and also potentially overcomes tumor microenvironment-mediated drug resistance and the downstream effects of genetic instability is thus urgently needed. Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM. ⋯ DARA may, therefore, be the first mAb with significant anti-MM activity both as a monotherapy and in combination. It is currently being further evaluated both alone and in combination with conventional and novel anti-MM agents as part of prospective clinical trials. This review discusses the preclinical and clinical development of DARA, its pathophysiological basis, and its prospects for future use in MM.