Pulmovant Highlights Positive Phase 1b ATMOS Study Results of Mosliciguat in Pulmonary Hypertension at ERS Congress

Pulmovant, a biotechnology company under Roivant, recently unveiled data from their Phase 1b ATMOS1 study at the European Respiratory Society Congress in Vienna. The study focuses on mosliciguat, an innovative inhaled soluble Guanylate Cyclase (sGC) activator designed for once-daily delivery to the lungs, targeting pulmonary hypertension (PH). 

The ATMOS1 trial assessed 38 patients and demonstrated a significant mean peak reduction in pulmonary vascular resistance (PVR) by up to 38%, marking one of the most substantial reductions observed in PH trials so far. The results indicated that the inhaled therapy, administered via a dry powder inhaler (DPI), was well tolerated with minimal treatment-emergent adverse events (TEAEs).

Mosliciguat's Phase 1 development program has extensively investigated its safety, efficacy, and convenience. It activates sGC independently of heme and nitric oxide (NO), unlike sGC stimulators that depend on these elements. This independence allows mosliciguat to maintain efficacy even in highly oxidative environments typical of PH. The enzyme sGC plays a crucial role in the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway, promoting vasodilation, reducing inflammation, and reversing vascular remodeling.

The Phase 1b ATMOS trial was a non-randomized, open-label, dose-escalation study evaluating the efficacy, safety, tolerability, and pharmacokinetics of mosliciguat in patients aged 18 to 80 years with World Health Organization (WHO) Group 1 and Group 4 PH. The study included 38 participants who received various doses of mosliciguat. Results showed peak percentage reductions in PVR from baseline of -25.9%, -38.1%, and -36.3% for doses of 1.0 mg, 2.0 mg, and 4.0 mg, respectively. These reductions consistently surpassed the predefined threshold for the primary outcome.

Mosliciguat's efficacy was also observed in patients non-responsive to inhaled NO, indicating its potential broad applicability across different PH types. Single-dose administration via DPI was well tolerated, with low rates of adverse events, further supporting its safety profile.

In its Phase 1 development, involving 170 participants, mosliciguat demonstrated favorable safety, dose-dependent cGMP increases, and a 40-hour half-life conducive to once-daily dosing. This distinguishes mosliciguat from other inhaled PH therapies that often require multiple daily inhalations. The DPI formulation offers greater convenience compared to nebulizers, reducing the risk of serious adverse effects associated with systemic vasodilators, such as oxygenation issues.

Pulmovant plans to advance mosliciguat into a global Phase 2 study named PHocus, targeting patients with PH associated with interstitial lung disease (PH-ILD), a subgroup of Group 3 PH. The study will enroll approximately 120 patients and is set to begin soon. PH-ILD affects around 200,000 individuals in the U.S. and Europe, presenting a significant unmet medical need due to the lack of approved treatment options.

Drew Fromkin, Pulmovant’s CEO, emphasized the importance of initiating the Phase 2 PHocus study, given the promising Phase 1b results and the urgent need for effective treatments for PH-ILD. He highlighted the severe impact of PH-ILD on patients' morbidity, mortality, and quality of life, expressing the company's commitment to improving outcomes for these patients.

Pulmonary hypertension is a progressive condition characterized by elevated blood pressure in lung vessels, leading to increased heart strain and symptoms like shortness of breath and fatigue. The WHO categorizes PH into five groups, with Group 3 PH linked to lung diseases such as interstitial lung disease (ILD). ILD encompasses a range of diseases causing lung damage, challenging patients' ability to breathe. PH-ILD, a subset of Group 3 PH, has limited treatment options, affecting a substantial patient population in the U.S. and Europe. 

Pulmovant is dedicated to developing innovative therapies for pulmonary diseases, with mosliciguat representing a promising once-daily inhaled treatment for PH.

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