Start of Phase IIIb Study with Bayer’s Riociguat in PAH Patients Who Demonstrate an Insufficient Response to PDE-5 Inhibitors
March 13, 2014
Bayer HealthCare announced today 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).
“A large proportion of PAH patients treated with PDE-5 inhibitors does not reach or maintain specific treatment goals,” said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. “The exact scientific reason for this insufficient response to treatment is still unknown. However, riociguat potentially has an advantage over PDE-5 inhibitors as the soluble guanylate cyclase (sGC) stimulator works independently from endogenous nitric oxide (NO) levels. The RESPITE study may provide the first clinical evidence on the potential clinical benefits of switching these PAH patients to riociguat.”
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. In the RESPITE study, 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 (defined as WHO Functional Class (FC) III, a six-minute walk distance (6MWD) of between 165 and 440m and a cardiac index of <2.5 L/min/m2) will be treated with riociguat for 24 weeks after a 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. The results of RESPITE are intended to be used as the basis for further investigations.
“In many guidelines and for many regulatory bodies worldwide, PDE-5 inhibitors are currently an established therapy for patients with PAH in WHO Functional Class II and III, and for many patients, they are a well-tolerated and effective treatment option,” said Principal Investigator Professor Marius Hoeper, Hannover University Medical School, Germany. “However, there is still a substantial number of PAH patients who do not reach treatment goals while receiving PDE-5 inhibitors. The RESPITE study is designed as a first step to provide important data on the clinical effects of riociguat in this particular patient population.”
Riociguat offers a new mode of action for the treatment of pulmonary hypertension (PH) that is different from that of PDE5-inhibitors, ERAs and PCAs. While ERAs and PCAs are effective synergistic therapies in combination with riociguat as they act on different therapeutic targets, concomitant use of the sGC-stimulator and PDE-5 inhibitors has to be avoided and is contraindicated as this may have an additive effect on systemic blood pressure.
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.
See the press release here.