Shares of Bellerophon Therapeutics Inc. (NASDAQ:BLPH), rescued from potential delisting by a recent reverse stock split, shot 168.4% higher to $9.20 on Feb. 18 as new top-line data from a small phase II study showed its inhaled nitric oxide delivery system, Inopulse, delivered significant improvements in blood flow for people with pulmonary hypertension (PH) associated with pulmonary fibrosis (PF).
The intrapatient dose-escalation study, called PHPF-002, found increased benefit for a 45-mcg/kg IBW/hr dose, adding new evidence to Bellerophon's belief that its portable drug delivery system offers measurable benefits to people with PH associated with idiopathic pulmonary fibrosis (IPF). People with the condition face a threefold increase in risk of death compared to IPF alone and, beyond lung transplantation, have limited therapeutic options.
Using catheterization to objectively measure the pulmonary arterial pressure of trial participants in real time, Bellerophon's study showed that "we have a really nice dose response that provides a very powerful hemodynamic benefit," CEO Fabian Tenenbaum told BioWorld.
Taken together with patient-reported outcome (PRO) data from phase II studies of Inopulse in the context of chronic care, Tenenbaum said the new data "clearly pave the road for the phase III," for which preparations are slated to begin this quarter. Depending on how quickly that work progresses, he said his team hopes to dose the first patient in the pivotal study in the near future. Depending on final details of its design, it will probably take between 12 months and 18 months, he said.
If successful, the company would move to file a simplified NDA through the 505(b)(2) pathway, incorporating safety data on inhaled nitric oxide for neonates, which is already FDA-approved.
Top-line results from PHPF-002 detailed Tuesday showed that acute treatment with Inopulse provided statistically and clinically significant improvements in hemodynamic parameters, the company said. Pulmonary vascular resistance was reduced by 21%, with an increased benefit (p<0.01) on dose escalation from iNO30 (30 mcg/kg IBW/hr) to iNO45 (45 mcg/kg IBW/hr). Mean pulmonary arterial pressure reduced by 12%. And inhaled nitric oxide was well-tolerated with no safety concerns across the doses, investigators reported.
The new data built on benefits seen in phase II, which found that participants on iNO30 and iNO45 were able to continue with moderate to vigorous physical activity (MVPA), defined as walking, climbing stairs, yard work and similar activities, while trial participants on placebo deteriorated. The treated patients, whose activity was measured by a purpose-built monitor, saw MVPA improved by 14 minutes per day. They also logged improvements via two PROs, the St. George Respiratory Questionnaire and University of California, San Diego Shortness of Breath Questionnaire.
"Taken together, we believe the acute hemodynamic dose response from the PHPF-002 study and the supporting phase II data present a strong case for the pulmonary vasodilation benefits of Inopulse," H.C. Wainwright & Co. analyst Andrew Fein said. "Furthermore, we note the company has reached FDA agreement on phase III cohort 3 to serve as the pivotal phase III study with MVPA as primary endpoint, assessing subjects with pulmonary fibrosis at low or intermediate/high risk of associated pulmonary hypertension.”
In September 2019, the FDA granted Bellerophon an orphan drug designation for nitric oxide in the treatment of IPF. In addition to IPF, Bellerophon is currently developing multiple product candidates under its Inopulse program, including for PH associated with chronic obstructive pulmonary disease and sarcoidosis.