This week in PVD

An investigational once-daily therapy, a single tablet combining macitentan and tadalafil, significantly improved pulmonary blood flow compared with macitentan or tadalafil alone in pulmonary arterial hypertension (PAH) patients taking part in the Phase 3 A DUE study.

Because these medications target different PAH-related pathways, current guidelines recommend initially treating PAH with both macitentan, sold as Opsumit, and tadalafil, sold as Adcirca.

“Targeting different pathways in the treatment of PAH has demonstrated clear clinical benefits, yet current treatment regimens are cumbersome and create a significant pill burden for patients, many of whom take a large number of pills each day to treat their PAH and various co-morbidities [co-existing conditions],” Kelly Chin, MD, a trial investigator and professor at the University of Texas Southwestern Medical Center, said in a press release.

NEW ORLEANS — Sotatercept, a novel activin signaling inhibitor, reduced risk for death and clinical worsening by 84% in patients with pulmonary arterial hypertension compared with placebo, according to results of the STELLAR trial.

“I am convinced that this is going to be a paradigm shift in the way we treat pulmonary hypertension patients,” Marius M. Hoeper, MD, deputy director of the department of respiratory medicine and head of the pulmonary hypertension program at Hannover Medical School, Germany, told Healio. “We will continue to use the currently available treatments as background therapy, but most physicians will use sotatercept early on in the course of the disease, and patients will advocate for it.”

A fixed-dose combination pill of macitentan and tadalafil outperformed monotherapy of either drug in patients with pulmonary arterial hypertension (PAH), according to new findings from the Phase III A DUE Study.1

The results, presented at the American College of Cardiology (ACC) 2023 Annual Scientific Sessions in New Orleans, Louisiana, indicated the combination of macitentan (10 mg) and tadalafil (40 mg) had approximately double the reduction in pulmonary vascular resistance (PVR) compared to either drug alone.

An experimental medicine for a rare blood vessel disorder improved patients’ exercise capacity and potentially slowed the disease’s progression, according to detailed results from a late-stage clinical trial that were revealed on Monday.

The drug, called sotatercept and owned by Merck & Co., was the principal prize of an $11.5 billion acquisition the pharmaceutical company negotiated more than a year ago.

Data from the trial were presented at a medical conference and published in The New England Journal of Medicine. They have been highly anticipated since October, when Merck said the study, dubbed STELLAR, was a success.

In patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), smoking status, community-acquired pneumonia (CAP), anion gap (AG), erythrocyte sedimentation rate (ESR), and serum magnesium (Mg2+) all were independently associated with the development of hyponatremia, according to findings from a multicenter, cross-sectional study published in the journal BMC Pulmonary Medicine.

Hyponatremia, a common electrolyte disorder that is defined as a low blood sodium level, is often seen in the general population and among hospitalized patients. In patients with COPD, hyponatremia is an independent predictor of poor prognosis, including increased morbidity and rehospitalization. Researchers therefore sought to evaluate the risk factors for and underlying etiologies of hyponatremia in patients with AECOPD.

Adding sotatercept to standard therapies significantly improved the six-minute walking distance by more than 40 meters (131 feet) compared with a placebo among adults with pulmonary arterial hypertension (PAH).

This finding met the primary goal of STELLAR, a Phase 3 clinical trial evaluating the impact of 24 weeks, or six months, of sotatercept on patients’ walking abilities.

The investigational therapy, developed by Merck, also led to statistically significant improvements in eight of nine secondary measures, including a marked reduction in clinical worsening or mortality risk.

“The results from the Phase 3 STELLAR trial are immensely important to physicians and patients and highlight the critical role sotatercept may play in improving exercise capacity and other meaningful clinical outcome measures for patients with PAH,” Dean Li, MD, PhD, president at Merck Research Laboratories said in a press release.

The accumulation of aggrecan, a protein found abundantly in cartilage, may be an early response to injury in the lungs of people with idiopathic pulmonary arterial hypertension, a study suggests.

Aggrecan accumulated preferentially in blood vessel lesions marked by high blood pressure in the lungs of idiopathic PAH (IPAH) patients. IPAH indicates pulmonary arterial hypertension of an unknown cause.

The findings support the potential of therapies to decrease aggrecan levels to halt the disease at its early stages, thereby “avoiding irreversible vascular fibrosis [scarring] and remodeling,” wrote the researchers in the study, “Aggrecan Accumulates at Sites of Increased Pulmonary Arterial Pressure in Idiopathic Pulmonary Arterial Hypertension,” which was published in Pulmonary Circulation.