In the Phase III study in patients with PAH a transient increase in mean heart rate of 3–4 bpm at 2-4 hours post-dose was observed. ECG investigations showed sinus tachycardia in 11.3% of patients in the selexipag group compared to 8.8% in the placebo group.- The sponsor can also confirm that it will monitor and report these events through Periodic Evaluation Reports (PBRERs). The updated AU PI is provided. It is that the The sponsor provides below a The sponsor’s sponsor has advised in benefit-risk assessment of the response is the PI that selexipag is various combination therapy satisfactory. effective in combination options studied in GRIPHON… with ERA and/or a PDE-5 inhibitor. It is Conclusion … also noted that A positive benefit-to-risk products treating PAH assessment has been established for often have common all subgroups of concomitant PAH safety concerns such as background therapies. Across all undesired subgroups by PAH background haemodynamic therapy, nearly identical efficacy changes. The sponsor was demonstrated for the primary should clarify whether study endpoint. The respective selexipag should be safety experience is largely defined avoided in combination by the profiles of the individual treatment with any drugs. Small differences in the other drug classes that incidence of individual AEs and are used for PAH. laboratory abnormalities do not affect the positive benefit-risk profile for any tested combination. The sponsor is of the opinion that selexipag in combination with an ERA, a PDE-5i or the combination of both is equally safe and effective. Overall, the concomitant use of other PAH-specific medications does not appear to present any additional safety concerns. The overall impact of selexipag on Hb is modest and the observed effects on the basis of concomitant medication showed no clear pattern. For hypotension, the effect of selexipag on blood pressure was small and there was a general absence of hypotension SAEs, irrespective of concomitant medication use. In terms of tolerability, concomitant use of other PAH medications resulted in an increase in the incidence of some
In the Phase III study in patients with PAH a transient increase in mean heart rate of 3–4 bpm at 2-4 hours post-dose was observed. ECG investigations showed sinus tachycardia in 11.3% of patients in the selexipag group compared to 8.8% in the placebo group.- The sponsor can also confirm that it will monitor and report these events through Periodic Evaluation Reports (PBRERs). The updated AU PI is provided. It is that the sponsor has advised in the PI that selexipag is effective in combination with ERA and/or a PDE-5 inhibitor. It is also noted that products treating PAH often have common safety concerns such as undesired haemodynamic changes. The sponsor should clarify whether selexipag should be avoided in combination treatment with any other drug classes that are used for PAH. The sponsor provides below a benefit-risk assessment of the various combination therapy options studied in GRIPHON… … Conclusion A positive benefit-to-risk assessment has been established for all subgroups of concomitant PAH background therapies. Across all subgroups by PAH background therapy, nearly identical efficacy was demonstrated for the primary study endpoint. The respective safety experience is largely defined by the profiles of the individual drugs. Small differences in the incidence of individual AEs and laboratory abnormalities do not affect the positive benefit-risk profile for any tested combination. The sponsor is of the opinion that selexipag in combination with an ERA, a PDE-5i or the combination of both is equally safe and effective. Overall, the concomitant use of other PAH-specific medications does not appear to present any additional safety concerns. The overall impact of selexipag on Hb is modest and the observed effects on the basis of concomitant medication showed no clear pattern. For hypotension, the effect of selexipag on blood pressure was small and there was a general absence of hypotension SAEs, irrespective of concomitant medication use. In terms of tolerability, concomitant use of other PAH medications resulted in an increase in the incidence of some The sponsor’s response is satisfactory.