Pfizer Inc. announced that Revatio(R) (sildenafil citrate)
has been approved by the European Commission for the treatment of pediatric
patients aged 1 to 17 years old with pulmonary arterial hypertension. Efficacy in
terms of improvement of exercise capacity or pulmonary hemodynamics has been shown
in primary pulmonary hypertension and pulmonary hypertension associated with
congenital heart disease.
“Pulmonary arterial hypertension is a rare, devastating
disease that can affect children,” said Dr. Cara Cassino, vice president,
Pfizer Medicines Development Group. “With the approval of Revatio, these young
patients now have an important treatment option that may help manage their
condition. This approval is another example of our ongoing commitment to rare
diseases.” The approval was based on results of a dose-ranging phase 3
study that evaluated the efficacy and safety of Revatio versus placebo in 234 pediatric
patients with primary pulmonary hypertension or pulmonary hypertension
associated with congenital heart disease. The primary endpoint was improvement
from baseline in exercise capacity as assessed by change in peak volume of
oxygen consumption (peak VO2) following 16 weeks of treatment. In children who
were deemed developmentally unable to perform the test due to young age or the presence
of other conditions, efficacy was assessed using secondary endpoints, including
hemodynamics and change in WHO functional class.
Estimated change in peak VO2 in evaluable patients receiving
any dose of Revatio was 7.71 percent (95 percent confidence interval: -0.19 percent
to 15.60 percent, P0.056). Dose-related improvements in pulmonary vascular
resistance index (PVRI) and mean pulmonary arterial pressure (mPAP) were
observed in patients treated with Revatio, and improvements in cardiac index
were observed with all three Revatio groups over placebo. Of 120 patients who
were WHO functional class II, III or IV at baseline who received Revatio, 32
improved by one functional class, and one subject improved by two functional
Four of the 35 patients in the placebo group improved by one
The adverse reaction profile seen in this pediatric study
was generally consistent with that in adults with pulmonary arterial hypertension
taking Revatio. Most adverse events were of mild to moderate severity and were
consistent with the known pharmacology of phosphodiesterase-5 inhibitors, the
class of medications to which Revatio belongs. The most common adverse
reactions observed in patients treated with Revatio were vomiting, cough,
pyrexia, nausea, lower abdominal pain, upper abdominal pain and photophobia.
Pulmonary arterial hypertension is a rare, progressive
disease characterized by high blood pressure in the pulmonary arteries, leading
to heart failure and premature death. Pulmonary arterial hypertension can occur
with no known underlying cause, or it can be found in association with other
disorders such as connective tissue disease or congenital heart disease.
For pediatric patients, Revatio will be available as an extemporaneously
prepared oral suspension compounded from Revatio 20 mg tablets and recommended
diluents. Revatio is also available in oral and I.V. formulations for the
treatment of adults with pulmonary arterial hypertension.
Revatio was first approved by the European Commission in
October 2005 for the treatment of adult patients with pulmonary arterial hypertension
classified as WHO functional class II and III, to improve exercise capacity.
Efficacy has been shown in primary pulmonary hypertension and pulmonary
hypertension associated with connective tissue disease. Revatio is approved for
the treatment of pediatric pulmonary arterial hypertension only in the EU, with
applications pending in other countries.
Since its initial regulatory approval in 2005, Revatio has
been approved and launched in more than 50 countries and has amassed more than
100,000 patient-years of experience.