September 22, 2016 – The pharmacologically active compound known as sildenafil is largely used to treat erectile dysfunction (on the market for this indication under the trade name Viagra) and pulmonary arterial hypertension (on the market for this indication under the trade name Revatio) in the United
States (US), the European Union (EU), and many other countries worldwide. Sildenafil, a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5) increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation. In patients with pulmonary arterial hypertension this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.
On 15 September 2016, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Granpidam, intended for the treatment of pulmonary arterial hypertension. As such, Granpidam is considered a generic of Revatio, which has been authorised in the EU since 2005. The indications for Granpidam are in adults the “treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity, and in the paediatric population the “treatment of paediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension”. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease, and in terms of improvement of exercise capacity or pulmonary haemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease.
What is strange in this context is the fact that apparently the “bioequivalence” of Granpidam has been determined against the Viagra and its indication “erectile dysfunction” as the reference medication that has already been on the market for a long time, and of which all the behaviours of the medication in the population in the main indication should be known. Apparently here, for Granpidam, “bioequivalence” was not determined against its intended indication “primary pulmonary hypertension”, and Revatio as the reference medication. Strange in the light of the fact that the indication of Granpidam is also for paediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension, where one would expect that erectile dysfunction would not play any role as a reference indication. One can only hope that the company has sound paediatric risk management plans (RMP) for paediatric patients in place and that previous or still valid paediatric investigation plans (PIP) are being adhered to.
You may also want have a look at the stance of the American Food & Drug Administration (FDA) on the use of Sildenafil (Revatio) in children. Thasso Post has an earlier report on this.