Drug (brand / generic)
Revatio / Sildenafil
Revatio is an approved formulation developed by Pfizer for the treatment of pulmonary arterial hypertension. The drug was first approved in June 2005 by the US Food and Drug Administration (FDA). In October 2005, Revatio was approved in the European Union. The intravenous formulation of Revatio was approved by the US FDA in November 2009.
Following US FDA approval of the intravenous formulation of Revatio in November 2009, the drug became the first treatment in its class to be available in both oral and intravenous dosage forms. The European Commission approved the intravenous formulation of Revatio in January 2010.
Pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is a chronic condition, which affects the heart and lungs. The disease is also known as high blood pressure of the lungs.
PAH is characterised by narrowed or blocked arteries, which increases the pressure on the heart to supply blood to the lungs. Prolonged pressure on the heart can weaken its blood pumping capability. As a result, less blood flows through the lungs, which decreases the amount of oxygen taken in by the body. The condition can lead to heart failure and premature death.
The exact cause of PAH is unknown, although new research is providing more information about the disease. It can affect men and women of all ages but it is more common among women between the ages of 20 and 40. The major symptoms of PAH include difficulty in breathing, dizziness, tiredness and chest pain.
As the disease progresses patients may find it difficult to carry out daily tasks. PAH may also be caused by heart and liver disease, connective tissue disease, HIV and Scleroderma. The main treatment options available for treating PAH include drugs that prevent blood clots and reduce swelling, oxygen therapy and PAH-specific therapies.
Pfizer’s Revatio (sildenafil)
Revatio contains sildenafil citrate as the active ingredient. Sildenafil is also sold as Viagra for erectile dysfunction. In patients suffering from PAH, Revatio dilates the blood vessels and reduces pulmonary vascular resistance. Revatio can be used with existing therapies in people who are not responding adequately to monotherapy.
Sildenafil works by inhibiting cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type-5 (PDE5). PDE5 causes the degradation of cGMP in the pulmonary vasculature muscle cells. By inhibiting PDE5, Sildenafil increases cGMP in the muscle cells, thus resulting in relaxation.
Sildenafil clinical trials
The clinical development of sildenafil involved 30 clinical trials, of which 24 were relevant for the treatment of PAH. Another 15 clinical trials were conducted after the approval of sildenafil. Revatio’s PAH development programme included two new pivotal clinical studies, A1481140 and A1481141.
The first clinical study, A1481140, was a 12-week multinational, multi-centre, double-blind, parallel group trial, which tested the safety and efficacy of three dose levels of sildenafil in PAH patients.
About 278 patients over the age of 18 suffering from PAH were enrolled for the study. Patients who were part of the A1481140 could enrol in a long-term extension study A1481142. The aim of the extension study was to evaluate the safety and efficacy of sildenafil 80mg in PAH patients.
The A1481141 study was a double-blind, placebo controlled study, which tested the use of sildenafil in combination with intravenous epoprostenol. The study enrolled 267 patients suffering from PAH.
In the clinical studies, it was observed that Revatio helped in lessening the impact of the symptoms of PAH in patients. Revatio also helped in alleviating the deteriorating conditions in PAH patients.
PAH marketing commentary
In 2009, it was estimated that the worldwide market for PAH was worth $2,653m.
The leading drug in the market for PAH is Actelion Pharmaceuticals’ Tracleer, which will be off patent in 2015. Other drugs include Remodulin, Flolan and Ventavis.
When Tracleer goes off patent, the market share of other drugs is expected to significantly improve. Revatio especially is better positioned over the other drugs with the approval of its intravenous formulation. Sales of the drug are expected to increase in the near future, posing tough competition to other drugs.
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