INOpulse Shows Promise in Proof-of-concept Trial for PH-Sarcoidosis
INOpulse, a device that administers inhaled nitric oxide, significantly improved blood flow parameters in a small proof-of-concept clinical trial conducted in people with pulmonary hypertension associated with sarcoidosis (PH-Sarc).
“We are pleased with the positive top-line data from this proof-of-concept study,” Naseem Amin, MD, chairman of the board of directors at Bellerophon Therapeutics, said in a press release. Bellerophon is the company developing INOpulse.
“Based on these results, Bellerophon is working with its steering committee, which is comprised of multiple pulmonary disease experts, to assess next steps for this program, including the design of a multi-dose Phase 2b study to assess the chronic benefit of iNO [inhaled nitric oxide] in PH-Sarc patients,” Amin said. “We look forward to continuing our development program in PH-Sarc.”
Pulmonary hypertension (PH) is a rare lung disease characterized by high blood pressure in the pulmonary arteries, which deliver blood from the heart to the lungs. The high pressure causes the heart to work harder to pump blood, which can lead to the heart becoming larger and weaker and eventually result in right heart failure.
Sarcoidosis involves the formation of small clumps of inflammatory cells called granulomas in different tissues and organs, most commonly in the lungs. In some patients, these granulomas are near the pulmonary arteries and veins and occlude and damage these vessels, leading to PH.
Nitric oxide is a gas that acts as a vasodilator — that is, it prompts blood vessels to relax and widen, which lowers blood pressure. The INOpulse device is about the size of a paperback book, is compatible with many long-term oxygen therapy systems, and is designed to deliver a steady dose of nitric oxide, according to Bellerophon.
The clinical trial (NCT03727451) enrolled eight people with PH-Sarc, who were being treated with long-term oxygen therapy. The participants were administered inhaled nitric oxide at doses of 30 to 125 micrograms per kilogram of ideal body weight per hour (mcg/kg IBW/hr). Seven of the eight participants escalated up to the highest dose.
Hemodynamic (blood flow-related) responses were measured via right heart catheterization, which involves surgically inserting a tube to measure pressure in the lung’s blood vessels. Specifically, researchers assessed mean pulmonary arterial pressure (mPAP), reflecting blood pressure in the lungs, and pulmonary vascular resistance (PVR), which denotes how hard the heart has to pump to move blood through the lungs.
Before treatment with INOpulse, the median mPAP was 37.2 mmHg, and the median PVR was 329 dyne/cm.sec-5 (a unit used to measure force).
Across the doses of inhaled nitric oxide, mPAP decreased by a median of 6–10%. As for PVR, it decreased by a median of 20%, which is generally considered to be clinically meaningful, at a dose of 45 mcg/kg IBW/hr. The highest dose, 125 mcg/kg IBW/hr, resulted in a median 29% decrease in PVR, which was statistically significant compared with the start of the trial.
No side effects associated with treatment or serious side effects were reported during the escalation to higher doses, the researchers reported.
“I am encouraged by the positive changes observed in multiple hemodynamic parameters in patients with sarcoidosis associated pulmonary hypertension being treated with long-term oxygen therapy and then acutely treated with INOpulse,” said Robert Baughman, MD, a professor at the University of Cincinnati and one of the trial’s principal investigators.
“Clinically meaningful improvements in PVR started at the [45 mcg/kg IBW/hr] dose and were well tolerated with no clinically relevant deterioration in pulmonary capillary wedge pressure or other hemodynamic parameters, even at the higher iNO doses,” Baughman added. “The results from this cohort of patients support further evaluation of the potential of iNO to treat PH-Sarc patients who are in urgent need of safe and effective therapies.”
The company is running a Phase 3 clinical trial called REBUILD (NCT03267108), which is testing the device in people with pulmonary fibrosis (scarring in the lungs) who are at risk of pulmonary hypertension.
“Bellerophon will continue to provide additional updates on our clinical activities in the coming year, including our ongoing Phase 3 program in fibrotic interstitial lung disease, the REBUILD study,” Amin said.