Bayer’s Adempas For CTEPH, PAH Confirmed Safe & Effective in Long-Term Studies

Findings collected during more than two years confirming the safety and efficacy of Bayer’s Adempas® (riociguat) in treating either inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), and patients with pulmonary arterial hypertension (PAH) were recently presented at the European Respiratory Society (ERS) Congress.

Riociguat is the first member of a new class of soluble guanylate cyclase (sGC) stimulators that target a key pathway of pulmonary hypertension (PH).

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The Six-Minute Walk Test, which was used for the endpoint in the riociguat studies, measures the exercise capacity in patients suffering from PH and is a marker of disease severity and survival. Now, the findings of the two-year CHEST-2 and PATENT-2 studies confirmed the results obtained previously by CHEST-1 and PATENT-1: improved exercise capacity and WHO Functional Class (FC).

Pisana Ferrari from the European Pulmonary Hypertension Association noted 

“The long-term results of these studies are very encouraging, as they substantiate that the improvements PAH or CTEPH patients experience with riociguat are sustainable over the long-term. For patients, this means improvements in their ability to walk farther, helping the heart and lungs work better, and making breathing easier when performing everyday basic tasks, and this ultimately suggests improved outcomes and prognoses.”

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A detailed analysis of CHEST-2 data in CTEPH patients treated for two-years with riociguat showed:

– An increased mean exercise capacity by 50m, when compared with the results of CHEST-1 trial.

– WHO FC improved and stabilized at 97% (specifically, 39% improved and 58% stabilized).

– A survival rate of 93%.

In the second study, PATENT-2, in PAH patients treated with riociguat for over two-years the overall analysis determined:

– an improvement of 47m in mean exercise capacity, compared with PATENT-1 trial baseline

– WHO FC improved and stabilized at 91% (33% improved, and 58% stabilized).

– A survival rate of 93%.

Professor Ardeschir Ghofrani, University Hospital Giessen and Marburg and Kerckhoff Heart and Lung Center, Bad Nauheim, Germany commented on these results, saying, “The positive results of CHEST-2 and PATENT-2 contribute to the growing evidence of riociguat as an effective and well-tolerated long-term treatment for two of the five types of pulmonary hypertension, having demonstrated in clinical trials early, significant and sustained benefits for patients. The correlation between patient-relevant parameters, such as 6MWD and WHO FC and event-free survival, underlines that close monitoring of patient’s symptoms and exercise capacity is important for predicting outcome and response to treatment.”

Riociguat was found to be safe and well-tolerated. The most common adverse reaction reported was dizziness, but dyspepsia, headache, and hypotension was also reported in 10 percent of patients taking riociguat treatment (up to 2.5 mg TID).

Pulmonary Hypertension  

Pulmonary hypertension (PH) is characterized by an increased blood pressure in the pulmonary arteries, with values above the normal baseline. As a result, the disease leads to heart failure and death in patients without treatment.

PH patients suffer from symptoms of shortness of breath, fatigue, dizziness and fainting, which tend to get worse with continued exercise activity. The PH diagnosis is often delayed due to the broad spectrum of symptoms exhibited by these patients. There are five different types of PH, and an early detection is vital for the correct diagnosis and follow-up treatment to these patients.

Riociguat
 

Riociguat is the first member of a new class of soluble guanylate cyclase (sGC) stimulators developed by Bayer.

PH is characterized by endothelial dysfunction and insufficient stimulation of an enzyme found in the cardiopulmonary system, sGC. sGC is the receptor for nitric oxide (NO). Upon binding with NO, sGC induces the synthesis of cyclic guanosine monophosphate (cGMP), which is important to regulate vascular tone, proliferation, fibrosis, and inflammation.

Riociguat features a novel dual mode of action, Riociguat, stabilizes NO-sGC binding and directly stimulates sGC independently of NO by targeting a different binding site. Hence, Riociguat bypasses NO deficiency and promotes cGMP synthesis. Moreover, Riociguat is the first drug capable of improving patients’ conditions with inoperable CTEPH, or persistent or recurrent CTEPH after surgical treatment. In October 2013, Riociguat was approved in the US under the name Adempas® to treat CTEPH and PAH.