MK-5475 / Merck (MSD) - LARVOL DELTA

Merck to Present New Clinical and Outcomes Research Data at The American Thoracic Society’s (ATS) 2025 International Conference Demonstrating Commitment to Advancing Research in Pulmonary Arterial Hypertension (Merck (MSD) Press Release) - "Merck...announced new clinical and outcomes research data on pulmonary arterial hypertension (PAH) to be presented at the American Thoracic Society’s (ATS) 2025 International Conference in San Francisco from May 16-21. Data from nine presentations demonstrate Merck’s commitment to advancing research for patients with this disease."

Clinical data • Pulmonary Arterial Hypertension

Long-term Safety of MK-5475 in Pulmonary Arterial Hypertension (PAH): Results From the Phase 2 INSIGNIA-PAH Extension Period (ATS 2025) - P2/3 | "MK-5475 was well-tolerated in patients with PAH on background therapies including PDE5is over approximately 1 year of median duration of exposure. Building upon prior data demonstrating the pulmonary selective vasodilatory activity of MK-5475, these data support the longer-term safety of MK-5475 and potential utility in patients with pulmonary hypertension."

Clinical • P2 data • Cardiovascular • CNS Disorders • Cough • Hematological Disorders • Hepatology • Hypotension • Infectious Disease • Liver Failure • Pain • Pneumonia • Pulmonary Arterial Hypertension • Respiratory Diseases • Ventricular Tachycardia

A Clinical Study To Understand How Radiolabeled MK-5475 Is Taken Up By The Body, Broken Down And Then Removed From The Body in Healthy Participants (MK-5475-011) (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

MK-5475-013 INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of MK-5475 (an Inhaled sGC Stimulator) in Adults With PH-COPD (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Mar 2028 ➔ Oct 2029

Trial completion date • Cardiovascular • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Inhaled MK 5475. Insights from the INSIGNIA trial. (CVCT USA 2024) - No abstract available

Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Inhaled MK-5475 for COPD-PH. (CVCT USA 2024) - No abstract available

Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

MK-5475, an inhaled soluble guanylate cyclase stimulator, for the treatment of pulmonary arterial hypertension, incl. discussion and Q&A (ERS 2024) - No abstract available

Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases

MK-5475, an inhaled soluble guanylate cyclase stimulator, for treatment of pulmonary arterial hypertension: the INSIGNIA-PAH study. (PubMed, Eur Respir J) - P2/3 | "In participants with PAH on stable background therapy, including PDE5i, inhaled MK-5475 reduced PVR and was well tolerated, without evidence of systemic side-effects such as hypotension, suggesting a pulmonary selective pharmacodynamic effect."

Journal • Cardiovascular • Hypertension • Hypotension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of the Efficacy and Safety of MK-5475 in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007) (clinicaltrials.gov) - P2/3 | N=168 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Phase 1 Study of MK-5475, an Inhaled Soluble Guanylate Cyclase Stimulator, in Participants with Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease. (PubMed, Int J Chron Obstruct Pulmon Dis) - P1 | "MK-5475 versus placebo led to numerical improvements from baseline in PVR (-21.2% [95% CI: -35.4, -7.0] versus -5.4% [95% CI: -83.7, 72.9]), with between-group difference in PVR less than -15% and calculated PP of 51%. The favorable safety profile and numerical reductions in PVR observed support further clinical development of inhaled MK-5475 for PH-COPD treatment."

Clinical • Journal • P1 data • P1 data • Cardiovascular • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of the Efficacy and Safety of MK-5475 in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007) (clinicaltrials.gov) - P2/3 | N=168 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting | N=450 ➔ 168 | Trial completion date: Jan 2028 ➔ Aug 2024 | Trial primary completion date: Feb 2026 ➔ Jan 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

MK-5475-013 INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of MK-5475 (an Inhaled sGC Stimulator) in Adults With PH-COPD (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Sep 2026 ➔ Mar 2028 | Trial primary completion date: Mar 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Cardiovascular • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

MK-5475-013 INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of MK-5475 (an Inhaled sGC Stimulator) in Adults With PH-COPD (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P2a ➔ P2

Phase classification • Cardiovascular • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A randomized study to evaluate the effects of single-dose MK-5475 co-administered with sildenafil on systemic hemodynamics (ERS 2023) - "Inhaled MK-5475 was well tolerated when administered on top of background sildenafil 20 mg TID, without effects on systemic hemodynamics versus placebo. The lack of additive systemic effects on blood pressure further documents pulmonary selectivity of inhaled MK-5475 including when co-administered with sildenafil.; Physiology; Respiratory intensive care; Epidemiology; General respiratory patient care; Public health; Pulmonary function testing"

Clinical • Cardiovascular • Critical care • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Phase 1 Study of MK-5475, an Inhaled Soluble Guanylate Cyclase Stimulator, in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) (ATS 2023) - P1 | "The favorable safety profile, absence of drug-induced arterial hypoxemia, lack of systemic hemodynamic effects, and numerical reductions in PVR observed in this Phase 1 study support further clinical development of inhaled MK-5475 for treatment of PH-COPD."

P1 data • Cardiovascular • Chronic Obstructive Pulmonary Disease • Congestive Heart Failure • Heart Failure • Hypertension • Immunology • Infectious Disease • Novel Coronavirus Disease • Pain • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

MK-5475-013 INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of MK-5475 (an Inhaled sGC Stimulator) in Adults With PH-COPD (clinicaltrials.gov) - P2a | N=120 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Effects of an inhaled soluble guanylate cyclase (sGC) stimulator MK-5475 in pulmonary arterial hypertension (PAH). (PubMed, Respir Med) - P1 | "Treatment with inhaled single-dose MK-5475 showed rapid and sustained reductions in pulmonary vascular resistance and increases in pulmonary blood volume. MK-5475 was generally well tolerated versus placebo without vasodilatory systemic side effects. The promising pulmonary selectivity and favorable safety/tolerability profile of MK-5475 seen in this study of adult participants with PAH lays the foundation for further clinical development."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of the Efficacy and Safety of MK-5475 in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007) (clinicaltrials.gov) - P2/3 | N=450 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2026 ➔ Jan 2028 | Trial primary completion date: Dec 2024 ➔ Feb 2026

Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

MK-5475-013 INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of MK-5475 (an Inhaled sGC Stimulator) in Adults With PH-COPD (clinicaltrials.gov) - P2a | N=120 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2a trial • Cardiovascular • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

MK-5475 in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) (MK-5475-006) (clinicaltrials.gov) - P1; N=22; Completed; Sponsor: Merck Sharp & Dohme Corp.; Active, not recruiting ➔ Completed; N=33 ➔ 22

Enrollment change • Trial completion • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

MK-5475 in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) (MK-5475-006) (clinicaltrials.gov) - P1; N=33; Active, not recruiting; Sponsor: Merck Sharp & Dohme Corp.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of the Efficacy and Safety of MK-5475 in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007) (clinicaltrials.gov) - P2/3; N=450; Recruiting; Sponsor: Merck Sharp & Dohme Corp.; Not yet recruiting ➔ Recruiting; Initiation date: Mar 2021 ➔ Jun 2021

Clinical • Enrollment open • Trial initiation date • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

MK-5475 in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) (MK-5475-006) (clinicaltrials.gov) - P1; N=33; Recruiting; Sponsor: Merck Sharp & Dohme Corp.; Trial completion date: Jul 2021 ➔ Feb 2022; Trial primary completion date: Jul 2021 ➔ Feb 2022

Clinical • Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of the Efficacy and Safety of MK-5475 in Participants With Pulmonary Arterial Hypertension (MK-5475-007) (clinicaltrials.gov) - P2/3; N=450; Not yet recruiting; Sponsor: Merck Sharp & Dohme Corp.

Clinical • New P2/3 trial • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases

A Study of Single Doses of MK -5475 on Pulmonary Vascular Resistance (MK-5475-002) (clinicaltrials.gov) - P1; N=25; Completed; Sponsor: Merck Sharp & Dohme Corp.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases