The European Medicines Agency (EMA), the European Union parallel to the U.S. Food and Drug Administration (FDA), advised that the therapy Adempas (riociguat) should not be prescribed to patients with PH associated with idiopathic interstitial pneumonia (PH-IIP).
According to a press release, EMA’s recommendation was supported by results of a Phase 2 trial that showed Adempas increases the risk of death and serious adverse events in patients with PH-IIP, compared to placebo.
The Phase 2 trial is called RISE-IIP (NCT02138825). The drug was previously approved for the treatment of pulmonary hypertension (PH).
IIP is a heterogeneous group of fibrotic lung disorders of unknown cause, among which idiopathic pulmonary fibrosis is the most common, characterized by inflammation and fibrosis in the lungs. PH is a common feature of IIP patients, occurring in 30-85% of cases, and associated with increased death rate. To date, there is no approved pharmacological therapy for PH-IIP patients.
Riociguat is a stimulator of soluble guanylyl cyclase (sGC) that increases vasodilation, helping reduce high blood pressure in the lungs. Approved for use in the U.S. in October 2013, and in the E.U. in March 2014, it was the first drug to be approved for chronic thromboembolic PH (CTEPH, WHO Group 4) and pulmonary arterial hypertension (PAH, WHO (World Health Organization Group) 1).
The RISE-IIP study, a randomized, double-blind, placebo-controlled, international trial, was designed to evaluate the safety and efficacy profile of riociguat in patients with symptomatic PH associated with IIP, a disease that belongs to WHO Group 3.
The trial involved 145 PH-IIP patients randomized to riociguat or placebo. At the time of the interim analysis that led to the termination of the study, 21 patients had died, 17 of which from the riociguat group.
Serious adverse events, such as respiratory diseases or lung infections, were also higher among patients assigned to the riociguat group leading to the assessment that the drug did not provide a clinically significant benefit for PH-IIP patients.
EMA will now update the product information to add a contraindication for patients with PH-IIP, and will inform the healthcare professionals of their recommendations to help ensure that Adempas is not given to patients with this condition.