Selexipag (1) – Uptravi®

• Clinical trials
  • The GRIPHON trial was a randomised, controlled, double-blind trial comparing selexipag with placebo.

Selexipag for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients in WHO functional class (WHO-FC) II to III, either as combination therapy in patients whose condition is inadequately controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase-5(PDE-5) inhibitor, or as monotherapy in patients who are not suitable for these treatments

• For patients in WHO functional class (WHO-FC) II to III, either as combination therapy in patients whose condition is inadequately controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase-5inhibitor, or as monotherapy in patients who are not suitable for these treatments; an additional benefit is not proven compared with the appropriate comparator therapy.
• Accordingly, the additional benefit of selexipag over the appropriate comparator therapy is not proven.
• The pharmaceutical manufacturer’s argument that, on the one hand, iloprost is the sole treatment option in the therapeutic indication and, on the other hand, the GRIPHON study covers the patient population for whom iloprost is not an option, cannot be accepted.
• It must therefore be assumed that, for approximately two-thirds of the study population, a patient-specific, optimised drug therapy, as determined by the doctor and taking into account the respective marketing authorisation status, would have been possible in the form of monotherapy with ERA or PDE-5-I or sGC-S, or a dual combination therapy of these active ingredients (INN), would have been possible.
• It should be noted that there is a discrepancy between the treatment situation in the GRIPHON study and the authorised therapeutic indication.
• In summary, treatment with placebo is inappropriate for the vast majority of patients in the study and, furthermore, does not constitute the appropriate comparator therapy.
• Consequently, the study submitted by the pharmaceutical manufacturer is not suitable for drawing conclusions regarding the additional benefit of selexipag compared with the appropriate comparator therapy.
• Conclusion
  • For the reasons set out above, the study submitted by the pharmaceutical manufacturer cannot be used to determine the additional benefit.

Courtesy translation only, please refer to the German original.