Mosliciguat’s early efficacy results support launch of Phase 2 study
Inhaled once-daily medication may offer safe, convenient option for PH
Treatment with mosliciguat, an inhaled medication given once-daily for pulmonary hypertension (PH), can safely reduce the resistance against blood flow in blood vessels of the lungs, according to a Phase 1 clinical trial.
This reduction in pulmonary vascular resistance (PVR) is one of the highest seen in PH trials to date, stated the treatment’s developer, Pulmovant.
Results were presented recently at the European Respiratory Society Congress in Vienna, Austria.
“We believe mosliciguat can transform the lives of patients living with pulmonary hypertension, and I am excited to announce this potential first-in-class and best-in-category therapy,” Matt Gline, CEO at Roivant Sciences, the parent company of Pulmovant, said in a press release.
PH is characterized by the narrowing of blood vessels that supply blood to the lungs. Mosliciguat is designed to widen blood vessels, even when there is low oxygen in the lungs and oxidative stress (which occurs when oxidant molecules outweigh the body’s antioxidant defenses), and it may have anti-inflammatory and antiscarring properties, according to Pulmovant.
Mosliciguat targets sGC enzyme that drives blood vessel widening
Mosliciguat targets soluble guanylate cyclase (sGC), an enzyme that ultimately drives blood vessel widening. Specifically, mosliciguat works in the nitric oxide/cGMP pathway, resulting in the production of the cGMP molecule.
To be effective, other sGC activators need heme, which is a ring-shaped compound that can bind nitric oxide. In contrast, mosliciguat does not require heme or nitric oxide to work. According to Pulmovant, this enables the treatment candidate to remain effective even in the highly oxidative environments typical of PH, as these environments can make sGC activators lose efficacy because heme is oxidized or removed, and nitric oxide levels are depleted.
The proof-of-concept Phase 1b clinical trial ATMOS (NCT03754660) assessed mosliciguat’s safety, tolerability, and efficacy in people with pulmonary artery hypertension or chronic thromboembolic pulmonary hypertension, a rare form of PH associated with blood clot formation.
A total of 38 participants, ages 18 to 80, received a daily dose of mosliciguat using a dry powder inhaler (DPI). In 20 patients, mosliciguat, administered at 1, 2, and 4 mg daily, achieved a mean reduction in PVR of 25.9%, 38.1%, and 36.3%, respectively, from the start of the study. These results exceeded the primary threshold of a minimum 20% reduction. A similar effect was seen in participants who did not respond to inhaled nitric oxide.
“We are impressed with the data generated so far, particularly the PVR results,” Gline said.
Phase 1 data support once-daily dosing of mosliciguat
Overall, along with a favorable safety profile in a total 170 healthy participants and PH patients during Phase 1, pharmacology data has supported once-daily dosing. This is a notable difference from current approved PH therapies that require multiple inhalations per day, Pulmovant stated.
The DPI formulation is more convenient for patients than nebulizers, which convert medications to an inhalable mist, according to the company. Also, direct lung delivery lowers the risk of side effects such as drops in oxygen levels, seen with blood vessel wideners given via other routes. This may make the treatment effective in different PH types, Pulmovant stated.
“Mosliciguat has the incredibly rare advantage of potential differentiation across three separate key areas — efficacy, safety, and convenience in administration,” Gline said.
Advancing with the mosliciguat clinical program, a Phase 2 trial called PHocus will enroll approximately 120 patients with PH associated with interstitial lung disease (PH-ILD), a condition that causes the lungs to become scarred.
“We have elected to initiate our global Phase 2 PHocus study in PH-ILD because of the lack of treatment options for patients coupled with the impressive Phase 1b results and strong biologic rationale,” said Drew Fromkin, Pulmovant’s CEO. “We are committed to making a significant difference for these patients and have assembled a stellar team, alongside our world-class investigators and advisors, to advance and optimize mosliciguat’s development.”
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