Experimental treatment improves blood flow in PH-ILD patients’ lungs
Inhaled therapy Mosliciguat now being tested in a Phase 3 clinical trial
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Mosliciguat, an inhaled treatment being developed by Pulmovant, was well tolerated and more effective than a placebo at improving blood flow through the lungs of adults with pulmonary hypertension associated with interstitial lung disease (PH-ILD), supporting its move into Phase 3 clinical testing, which is already underway.
That’s according to top-line results from PHocus (NCT06635850), a global Phase 2 clinical study involving 135 patients in which a once-daily breath of mosliciguat more than halved pulmonary vascular resistance (PVR), a measure of how much resistance blood faces as it moves through the blood vessels in the lungs.
Based on these results, the company has started a Phase 3 clinical study in three U.S. locations, called PHrontier (NCT07816185), which is planned to enroll about 375 adults with PH-ILD. Patients will be randomly assigned to receive mosliciguat or a placebo for 24 weeks (about six months) and may then continue into an extension period, during which all patients will receive mosliciguat.
“We are truly grateful to the patients, investigators, and site teams who made this study possible,” Drew Fromkin, CEO of Pulmovant, said in a company press release. “We are also pleased to announce that our Phase 3 PHrontier study for patients with PH-ILD has been initiated with the goal of rapidly bringing mosliciguat to patients.”
Mosliciguat designed to ease PH-ILD symptoms
In PH-ILD, abnormally high pressure in the vessels that deliver blood from the heart to the lungs is caused by lung diseases that gradually damage and scar the lungs, making it difficult for the heart to pump blood through the lungs. Approved treatment options are limited to inhaled treprostinil, available in the U.S. as Tyvaso, Tyvaso DPI, and Yutrepia.
“Today, the treatment landscape is sparse, primarily consisting of formulations of inhaled treprostinil and their associated limitations, and off-label use of PDE5 [phosphodiesterase 5] inhibitors,” Fromkin said. “Mosliciguat has demonstrated that it may address many of these treatment gaps.” Formulations of treprostinil and PDE5 inhibitors are approved for pulmonary arterial hypertension.
Mosliciguat is designed to activate an enzyme called soluble guanylate cyclase, which is involved in a signaling pathway that uses nitric oxide and cyclic guanosine monophosphate (cGMP). Increasing cGMP can relax blood vessels, known as vasodilation, making it easier for blood to flow through the lungs. This is expected to ease symptoms of PH-ILD.
These results represent a clinically meaningful advancement in this field and highlight the potential of mosliciguat to address a longstanding gap in care.
The fully enrolled PHocus study is testing how safe mosliciguat is and how well it works compared with a placebo in adults with PH-ILD. Patients were randomly assigned to receive either mosliciguat or the placebo for 24 weeks, after which they could join an open-label extension in which all patients receive the experimental treatment.
The study met its main goal. After 16 weeks (about four months), patients receiving mosliciguat had a 56.3% greater reduction in PVR than those receiving the placebo. The actual change was a 51.3% reduction with mosliciguat compared with a 6.6% increase with the placebo. All patients receiving mosliciguat experienced a reduction in PVR, according to a webcast hosted by Roivant, which owns Pulmovant.
“The PVR reduction observed in PHocus is remarkable and among the largest reported,” said Marc Humbert, MD, PhD, a professor at Université Paris-Saclay in France, who presented the results at the European Respiratory Society congress in Barcelona. “These results represent a clinically meaningful advancement in this field and highlight the potential of mosliciguat to address a longstanding gap in care.”
Study achieved both secondary goals
The study also achieved its two secondary goals. One measured how far patients could walk in six minutes, known as the six-minute walk test. On average, patients receiving mosliciguat walked 20.3 meters (66.6 feet) farther after 16 weeks of treatment, while those receiving the placebo walked 14.9 meters (48.9 feet) less in six minutes.
The other secondary goal was to watch for changes in circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker that indicates strain on the heart. Lower levels of NT-proBNP in the blood can indicate that the heart is under less strain. After 16 weeks, mosliciguat produced a 53.2% reduction in NT-proBNP compared with the placebo.
In a prespecified exploratory analysis at 24 weeks, meaning an analysis planned before the results were known that is not one of the main goals of the study, the distance walked in six minutes increased an average of 52.7 meters (172.9 feet) with mosliciguat compared with the placebo. NT-proBNP was reduced by 75.9% compared with the placebo.
Mosliciguat was also well tolerated. Reported side effects were generally consistent with those expected from PH-ILD itself. Cough occurred in 12.1% of patients receiving mosliciguat compared with 18.2% receiving the placebo, which is notable because cough can be a common side effect with other inhaled treatments for pulmonary hypertension.
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