Bayer's Investigational Riociguat Granted FDA Priority Review for Pulmonary Arterial Hypertension

April 8, 2013—Bayer HealthCare Pharmaceuticals, Inc. (Wayne, NJ) announced that the New Drug Application (NDA) for its oral investigational compound, riociguat, has been accepted for filing and granted priority review by the US Food and Drug Administration (FDA) for the treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent or recurrent CTEPH after pulmonary endarterectomy (PEA) and pulmonary arterial hypertension (PAH).

As noted in the company's announcement,
 riociguat (BAY 63-2521) is an investigational oral soluble guanylate cyclase (sGC) stimulator that is being studied in CTEPH and PAH, as well as other forms of pulmonary hypertension. Riociguat was discovered and developed at the Bayer research laboratories. It is an investigational agent and is not approved by any health authorities.

In its press release, the company noted that both CTEPH and PAH are life-threatening diseases. CTEPH is a form of pulmonary hypertension in which blood clots and thromboembolic occlusion of pulmonary vessels leads to increased pressure in the pulmonary arteries. PAH is a disease characterized by elevated pressure in the pulmonary arteries.

The FDA grants priority review to medicines that provide a treatment where little or no adequate therapy exists. Under the Prescription Drug User Fee Act (PDUFA), the FDA aims to complete its review within 6 months of the 60-day filing receipt of the NDA submission (8 months total), rather than the standard 12-month review cycle.

According to Bayer, the NDA submission is supported by data from two global Phase III studies of riociguat: CHEST-1 and PATENT-1. Data from these two studies were presented in October 2012 at CHEST, the annual meeting of the American College of Chest Physicians. Both Phase III studies on riociguat met their primary endpoint.

CHEST (Chronic Thromboembolic Pulmonary Hypertension sGC-Stimulator Trial) is a phase III trial to assess the efficacy and safety of oral riociguat in the treatment of patients with either inoperable CTEPH or CTEPH that has persisted or reoccurred after PEA. CHEST is a multicenter, multinational program with active centers in 26 countries. The program includes a randomized, double-blinded, placebo-controlled trial phase (CHEST-1) and an open label extension trial phase (CHEST-2).

In the CHEST-1 study, 261 patients with inoperable CTEPH or with persistent or recurrent CTEPH after PEA were randomized and treated with either riociguat or placebo orally for 16 weeks. The primary endpoint of the trial was improvement in 6-minute walking distance. Riociguat was titrated, over a period of 8 weeks in doses of 0.5-mg increments, from 1.0 mg up to 2.5 mg, three times a day. After the titration phase, patients were followed for another 8 weeks on their last dose to complete CHEST-1. Patients from both arms then had the option of participating in the open label extension study (CHEST-2) after completing an 8-week blinded sham titration. CHEST-2 is continuing to investigate riociguat in CTEPH patients.

PATENT (Pulmonary Arterial Hypertension sGC-Stimulator Trial) is a phase III trial to assess oral riociguat in the treatment of treatment-naive patients and pretreated patients with symptomatic PAH. PATENT is a multicenter, multinational program with active centers in
 32 countries. The program includes a randomized, double-blind, placebo controlled trial phase (PATENT-1) and an open-label extension trial phase (PATENT-2).

In the PATENT-1 study, 445 patients with symptomatic PAH were randomized to receive either placebo or two different doses of riociguat orally over a period of 12 weeks. The primary endpoint of the trial was improvement in 6-minute walking distance. The riociguat dose was titrated, over a period of 8 weeks in doses of 0.5-mg increments, from 1.0 mg up to 2.5 mg, three times daily. Patients were then followed for an additional 4 weeks to complete the study. Patients then had the option of participating in the open-label extension study, after completing an 8-week blinded sham titration, according to Bayer HealthCare's press release.