Pfizer’s Revatio flunks paediatric hypertension study

An attempt by Pfizer to extend the uses of its pulmonary artery hypertension (PAH) drug Revatio into a new paediatric indication has had a major setback.

Revatio (sildenafil citrate) – which is based on the same PDE5 inhibitor active ingredient as Pfizer’s Viagra erectile dysfunction drug – failed to show any additional benefit when combined with inhaled nitric oxide (iNO) for the treatment of infants with persistent pulmonary hypertension (PPHN), an uncommon but life-threatening disorder.

PPHN happens when the normal circulatory shift that follows the first cry after birth goes wrong. The shift – also known as a shunt – allows newborns to use their lungs to breathe, rather than relying on oxygen delivered via the umbilical cord and placenta.

It happens in around two in 1,000 births, with affected infants treated with a ventilator and iNO to open up closed blood vessels in the lungs and reduce blood pressure.

Pfizer was testing whether adding intravenous Revatio to iNO could reduce the risk of treatment failure, defined as death or need for a heart bypass-like machine that delivers extracorporeal membrane oxygenation (ECMO), or shorten the time that patients needed to be taking iNO.

Its drug failed on both those measures in the first phase (Part A) of the study, missing its primary objectives. A follow-up portion of the study (Part B) is still ongoing and will look at how well the infants fare in the two years after treatment for PPHN, but with the primary endpoint missed the trial is a bust.

Revatio has been approved as a treatment for PAH in adults in the US since 2005, extending the sildenafil franchise that has been a staple of Pfizer’s product portfolio since Viagra was approved as the first oral therapy for ED in the late 1990s. It is also approved for the treatment of paediatric PAH in the EU and Japan.

Revatio extended the patent life of the franchise, but generics of the product first appeared in 2012. Earlier this year the FDA approved the first generic of an oral suspension formulation of the drug developed by Novitium Pharma. Revatio is currently included on the FDA’s drug shortages list.