Date: 2014-03-13
Type of information: Recruitment of the first patient
phase: 3b
Announcement: recruitment of the first patient
Company: Bayer Healthcare (Germany)
Product: riociguat
Action
mechanism: Riociguat (BAY 63-2521) is an oral agent being investigated as a new approach to treating different types of pulmonary hypertension. Riociguat is the first member of a novel class of compounds, the stimulators of enzyme found in the cardiopulmonary system, soluble guanylate cyclase (sGC). When nitric oxide (NO) binds to sGC, the enzyme catalyzes synthesis of the signaling molecule cyclic guanosine monophosphate (cGMP), which plays an important role in regulating vascular tone, proliferation, fibrosis, and inflammation.
The ability of riociguat to directly stimulate sGC independent of NO while also increasing the sensitivity of sGC to NO is potentially important in PAH. Endothelial dysfunction associated with PAH can be related to low levels of NO.
Disease: pulmonary arterial hypertension (PAH)
Therapeutic area: Rare diseases - Cardiovascular diseases
Country:
Trial
details: The RESPITE study is designed to evaluate the clinical effects of riociguat in patients with pulmonary arterial hypertension (PAH) who demonstrate an insufficient response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) either as monotherapy or in combination with an endothelin receptor antagonist (ERA). Approximately 60 PAH patients pre-treated with either sildenafil or tadalafil for at least three months, and who demonstrate an insufficient clinical response to PDE-5 inhibitor therapy, a six-minute walk distance (6MWD) of between 165 and 440m and a cardiac index of wash-out phase. Outcome variables being assessed in this exploratory study include changes in 6MWD, cardiac index, Quality of Life, WHO FC, clinical worsening, and other disease-related parameters as well as nitric oxide biomarkers.
Latest
news: * On March 13, 2014, Bayer HealthCare has announced the enrolment of the first patient in an open-label, multicentre, multinational Phase IIIb pilot study, RESPITE (Riociguat clinical Effects Studied in Patients with Insufficient Treatment response to PDE-5 inhibitors). The RESPITE study is designed to evaluate the clinical effects of riociguat in patients with pulmonary arterial hypertension (PAH) who demonstrate an insufficient response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) either as monotherapy or in combination with an endothelin receptor antagonist (ERA).
In the pivotal Phase III clinical trial PATENT-1, riociguat was shown to be the first oral treatment with robust efficacy across multiple clinically relevant endpoints in patients with PAH, either as a monotherapy or in combination with ERA or prostacyclin analogue (PCA) therapies. So far no other oral drugs, including PDE-5 inhibitors, have been able to show this. To date, there is no clinical data available to inform physicians if replacement of PDE-5 inhibitors with riociguat is safe and if it is associated with clinically relevant improvements in patients who are not at treatment goal with PDE-5 inhibitors.
Riociguat was approved under the name Adempas® in the US as the first and only drug for use in two forms of PH, chronic thromboembolic pulmonary hypertension (CTEPH) and PAH in October 2013. In Canada, the approvals for CTEPH and PAH followed in September 2013 and March 2014 respectively. In Switzerland and Japan, riociguat was approved in the CTEPH indication in November 2013, and in January 2014 respectively. In January 2014, the European Committee for Medicinal Products for Human Use (CHMP) recommended approval for riociguat in CTEPH and PAH, and in February 2014, the European Committee for Orphan Medicinal Products (COMP) confirmed the significant benefit of riociguat over existing treatments. In the opinion of the COMP, riociguat demonstrated a clinically relevant benefit for PAH patients in monotherapy and in combination, thereby confirming the orphan drug designation for riociguat.
