- Medicines and Healthcare products Regulatory Agency
- 8 August 2016
- Therapeutic area:
- Cardiovascular disease and lipidology and Respiratory disease and allergy
Patients with pulmonary hypertension associated with idiopathic interstitial pneumonias should not be treated with riociguat in light of interim results from a recently terminated study.
Advice for healthcare professionals:
- patients with pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP) should not be treated with riociguat. PH-IIP is not authorised indication for riociguat
- riociguat treatment should be discontinued in any patient with PH-IIP. The patient’s clinical status should be carefully monitored after stopping riociguat
- the benefits of riociguat in its approved indications (see below) continue to outweigh the risks
Riociguat (Adempas) is authorised for use in patients with WHO Functional Class II–III inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent or recurrent CTEPH after surgery, and in patients with WHO Functional Class II–III pulmonary arterial hypertension (PAH).
RISE-IIP was a randomised, double-blind, placebo-controlled, multicentre phase II trial to investigate the efficacy and safety of riociguat in 145 patients with symptomatic PH-IIP—an unapproved indication. The primary endpoint was change in the 6-minute walking-distance test after 26 weeks of treatment.
Early termination of trial
The trial was terminated early on the basis of interim results that showed increased mortality and increased risk of serious adverse events in the riociguat group compared with the placebo group.
Moreover, preliminary data indicated that riociguat did not provide a clinically significant benefit for these patients.
At the time of the interim assessment leading to termination of the trial, 21 deaths had been observed: 17 patients assigned riociguat and 4 assigned placebo. Serious adverse events, which were mainly respiratory disease or lung infections, were also higher in the riociguat group than in the placebo group.
In light of these findings, product information for riociguat will be updated to contraindicate the use of riociguat in patients with PH-IIP. The benefits of riociguat in its approved indications continue to outweigh the risks.
Studies of riociguat in patients with PAH have mainly assessed forms related to idiopathic PAH, heritable PAH, and that associated with connective-tissue disease. Use of riociguat in other forms of PAH that have not been studied is not recommended (further information is given in sections 4.4 and 5.1 of the Summary of Product Characteristics).
European Medicines Agency statement for riociguat, 24 June 2016
Article citation: Drug Safety Update volume 10 issue 1, August 2016: 1.
Published: 8 August 2016