On September 30, Bellerophon Therapeutics published results from clinical trials performed for investigational therapy INOpulse® on patients with pulmonary arterial hypertension (PAH) associated with chronic obstructive pulmonary disease (COPD). The results were presented at the European Respiratory Society (ERS) International Congress 2015 (Amsterdam) during the session reserved for “Pulmonary hypertension: new treatment insights.” The abstract entitled “Pulmonary vascular effects after pulsed inhaled NO evaluated by functional respiratory imaging (FRI)” was presented by W. De Backer, M. D., Director Department of Pulmonary Medicine, University Hospital and University of Antwerp.
Pulmonary arterial hypertension is a rare lung disorder in which the arteries that move blood from the heart to the lungs become narrowed. This narrowing makes it difficult for blood to flow through the vessels, yielding an increase in blood pressure above normal levels. Though PAH occurs in individuals of all ages, races, and ethnic backgrounds, it is more common in young adults, and females are more likely to be affected by PAH than adult males. In the US, statistics indicate that more than 20,000 people are diagnosed with PAH every year, and the five-year survival rate after diagnosis is estimated to be about 57%. Several risk factors have been identified as causing PAH including genetic predisposition, low oxygen conditions, some classes of medications and other medical problems like chronic obstructive pulmonary disease (COPD). It is believed that the process starts with injury to the layer of cells that line the small blood vessels of the lungs due primarily to excess proliferation of the pulmonary artery smooth muscle cells. This in turn induces narrowing of blood vessels, resulting in various symptoms of patients with PAH as shortness of breath, irregular heartbeat, racing pulse, dizziness, and rarely coughing up blood.
From a therapeutic viewpoint, several classes of medications are available, including calcium channel blockers, endothelin receptor antagonists, activators of soluble guanylate cyclase, and prostaglandins, among others. Each class of medication has variable efficiencies and side effects, and are designed for variable disease severity, progression, and patient’s drug tolerance. However, it is generally accepted that inhaled drugs are more efficient than oral forms because the drug is directly delivered through the lungs.
As a result, Bellerophon is currently developing two product candidates under the program INOpulse® with proprietary pulsatile nitric oxide delivery device. The first drug designed to treat PAH enters Phase 3 clinical trials in 2015, and the second is designed to treat PAH associated COPD, which is currently in Phase 2 development. In this Phase 2 study, a total of 6 patients (3 women and 3 men) aged between 65-79 years suffering from PAH associated COPD with long-term history of oxygen therapy have participated. The patients were administrated an acute dose of INOpulse® inhaled nitric oxide. Afterwards, the patients were subjected to test imaging to figure out the geometry of their lungs airway and pulmonary vascular architecture. The results indicated that blood volume in lungs vessels has increased and oxygen saturation was preserved after treatment with INOpulse® inhaled nitric oxide. Also, the participating patients noted that their conditions improved after treatment.
In summary, INOpulse inhaled nitric oxide appears to be a promising treatment for PAH associated COPD. The results from the clinical trials showed improved vasodilation in patients with PAH associated COPD. In 2016, Bellerophon plans on testing INOpulse on patients with PAH associated with COPD and idiopathic pulmonary fibrosis.
“We continue to be encouraged by the progress we are making in the development of INOpulse as a potential treatment for pulmonary hypertension. This late-breaker session at the ERS Congress builds on earlier studies indicating that INOpulse has the potential to reduce pulmonary hypertension in COPD patients. In the next several months, we plan to test the effect of reducing pulmonary hypertension on exercise capacity for these patients,” stated Jonathan Peacock, Chairman and Chief Executive Officer of Bellerophon Therapeutics.