Expert opinion on investigational drugs
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Pulmonary hypertension (PH) is a severe condition with a poor prognosis despite recent treatment advances. Therapies with new mechanisms of action are needed. ⋯ Cyclic guanosine monophosphate (cGMP) is an important mediator of the preferential perfusion of well-ventilated regions throughout the lung. Drugs that increase cGMP levels could promote pulmonary vasorelaxation while maintaining optimal gas exchange. cGMP is generated by sGC, which can be stimulated by nitric oxide (NO). Riociguat stimulates sGC independently of NO and increases the sensitivity of sGC to NO, resulting in increased cGMP levels. Results to date suggest rapid, potent and prolonged efficacy and good tolerability in different types of PH. Phase III clinical trials are evaluating the long-term safety and clinical effectiveness of riociguat in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH. Riociguat has the potential to become an important drug for the treatment of patients with PH.
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Expert Opin Investig Drugs · Apr 2011
ReviewInvestigational factor Xa inhibitors for thrombosis and acute coronary syndromes.
A number of new oral anticoagulant drugs that selectively and directly inhibit factor Xa (FXa) appear as promising alternatives to the existing anticoagulant agents. These compounds present a convenient route of administration with predictable pharmacokinetics and pharmacodynamics that allow fixed dosing regimens without requiring coagulation monitoring. Rivaroxaban is the first of this new class of drugs that was approved for the prevention of venous thromboembolism (VTE) after elective total hip replacement or total knee replacement surgery in the EU, Canada and several other countries. Clinical trials with rivaroxaban in patients with acute VTE and in patients with atrial fibrillation have been recently completed. Numerous other compounds are under different developing stages (apixaban, edoxaban, otamixaban, LY517717, PRT-054021, YM150). ⋯ Undoubtedly, these new drugs will offer several advantages over the previous compounds, but a number of issues still require some attention during the phase of translation from clinical trials into daily clinical practice.