Top 10 Pulmonary Hypertension Stories of 2019

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Over the last year, Pulmonary Hypertension News has brought you the latest news about groundbreaking discoveries, treatment developments, clinical trials, and other events related to pulmonary hypertension (PH).

As we look ahead to 2020, here are our top 10 most-read stories of 2019, with a summary of their significance for the PH community.

No. 10 — “Antibody Able to Block Protein That Promotes PAH and May Bolster Existing Therapies, Study Finds

Osteoprotegerin (OPG) is a protein that helps to regulate bone density, and it also affects the growth and migration of smooth muscle cells — which is why it is believed to play a role in pulmonary arterial hypertension (PAH). A study showed that blocking OPG with an antibody specific to the protein could halt, and even reverse, the progression of PAH in mouse and rat models. Furthermore, combining this antibody to treatment with Revatio (sildenafil) or Tracleer (bosentan) lessened blood vessel modeling to a greater extent than treatment with either therapy alone.

No. 9 — “Actelion Needs Further Studies on Opsumit Treatment for Inoperable CTEPH, US FDA Says

In a Phase 2 clinical trial (NCT02021292) testing the endothelin receptor antagonist Opsumit (macitentan) in people with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), the therapy was found to be well-tolerated and to significantly increase exercise tolerance. Based on these positive results, Actelion, the company developing Opsumit, submitted a supplemental new drug application to the U.S. Food and Drug Administration (FDA). But the agency, in a complete response letter, stated that further studies are needed to accurately assess the use of Opsumit in the treatment of inoperable CTEPH.

No. 8 — “Udenafil Can Increase Exercise Capacity in PAH Patients, Phase 2 Trial Results Show

Udenafil is an experimental therapy that works similarly to Revatio, but it lasts longer in the body. In a Phase 2b clinical trial (NCT01553721), treatment with udenafil resulted in a significantly higher average increase in exercise capacity — as measured by the six-minute walking distance (6MWD) test — than did treatment with a placebo (46 vs. 21 meters, or about 150 vs. 69 feet). There were no differences between treatment groups in terms of subjective exertion (how a person subjectively perceives his or her exertion), but those on udenafil did have significantly lower levels of a marker of stress on the heart than did those on placebo. The treatment was generally well-tolerated.

No. 7 — “Long-term Adempas Treatment May Reverse Right Heart Deficits in Patients with PAH, CTEPH, Study Finds

Researchers analyzed data from several clinical trials in which Adempas (riociguat, marketed by Bayer) was used to treat people with PAH or CTEPH. They found that PAH or CTEPH patients given Adempas had significant reductions in the thickness of the right heart muscle as soon as three months after initiating treatment, and this benefit persisted for at least one year. Similar improvements in the heart’s pumping capacity, and in patients’ overall exercise capacity, were also seen.

No. 6 — “United Therapeutics Gains Global Rights to Potential PAH Therapy Ralinepag

Ralinepag (APD811) is an investigational PH therapy that acts as a vasodialator (a compound that widens blood vessels, so the pressure within them decreases). It is currently being investigated in a Phase 3 clinical trial (NCT03626688), following promising results from a Phase 2 trial (NCT02279160). Ralinepag was originally developed by Arena Pharmaceuticals, but under the terms of a 2018 licensing agreement, now effective, rights to the therapy belong to United Therapeutics. Under the agreement, United Therapeutics has exclusive, global rights to develop and produce ralinepag; in return, Arena received an upfront cash payment, and may earn more if certain regulatory milestones are achieved, in addition to royalties on ralinepag sales.

No. 5 — “High Cardiac Troponin Levels Linked to Poor Outcomes in PH, Study Shows

Troponin is a protein complex that is important for the function of muscles, including muscles of the heart. Accumulating evidence suggests that high levels of cardiac troponin (cTn) is linked with poorer outcomes in PH. Researchers analyzed data from 739 people with PH, available in eight previously published articles, and found that people with PH and high cTn levels had a significantly higher mortality rate than those with normal cTn levels (48.8% vs. 18.6%). These results appeared to link high cTn levels with a more than three times increase in mortality risk in PH patients.

No. 4 — “Opsumit Has Potential to Improve Right Ventricle Function in PAH Patients, Phase 4 Data Show

A preliminary analysis of 42 PAH patients treated with Opsumit as part of the Phase 4 REPAIR (NCT02310672) clinical trial showed that, after 26 weeks of treatment, there was a significant increase in average right ventricular systolic pressure (by 16.6 mL) and a reduction in pulmonary vascular resistance (by 37%), compared with measures taken before the treatment. These data suggest that Opsumit can improve the function of the heart’s right ventricle, the part of the heart that pumps blood to the lungs. No new safety issues associated with Opsumit’s use were reported in the study.

No. 3 — “Mouse Study Finds Causal Link Between Iron Levels and Pulmonary Hypertension

Iron deficiency has been linked to an increased risk of PH, but the reasons for this association have not been well-understood. A study found that a lack of iron in muscle cells lining the circulatory system in the lungs sets off a chain of events that results in PH development. Further research demonstrated that this association was mediated, at least in part, by a protein called ET-1, which was present at unusually high levels in cells with low iron levels. Additionally, a PH-associated mutation in the BMPR2 gene impaired iron storage processes in cells, suggesting a link between irregular iron levels in cells and familial PH.

No. 2 — “Study Links Pulmonary Arterial Pressure Greater than 30 mmHg to Increased Mortality

PH is generally defined as an estimated right ventricular systolic pressure (RVSP) of 25 mmHg or greater, but there exists a need for the identification of more specific thresholds that can distinguish different degrees of risk in PH. In a study of 157,842 people with PH in Australia, statistical analyses revealed that a RVSP of 30 mmHg or higher was associated with a statistically significant increase in mortality risk. Those with a RVSP between 30.0-39.9 mmHg were, after adjusting for other relevant factors, 1.4 to 1.9 times more likely to die compared to patients with lower RVSP levels.

No. 1 — “CHEST Releases Updated Guidelines for PAH Treatment

The American College of Chest Physicians (CHEST) released the fourth version of guidelines for PAH care, expanding on the previous guidelines released in 2014. The updated guidelines were based on expert review of available evidence, particularly research published in the last five years. Among the new recommendations are the addition of Adcirca (tadalafil, marketed by United Therapeutics in the U.S.) to treatment regiments of Letairis (ambrisentan, marketed by Gilead in the U.S.), as well as the inclusion of palliative care services for people with PAH, and patient participation in exercise activity under expert supervision as part of their care regime.


Pulmonary Hypertension News hopes these stories, and our continued reporting throughout 2020, aid in educating and informing about PH, and help to improve the lives of people with the disease and their loved ones.

We wish all our readers a happy and inspiring 2020.