Experts urge government support for life-saving pulmonary arterial hypertension drugs

Pulmonary arterial hypertension, a frequent and potentially fatal condition for women in their 40s, badly needs government support for its treatments, experts say, pointing out that there are good treatments available but cannot be used.

Last Friday, the Korean Pulmonary Hypertension Society held a press conference on the topic of “How to improve the survival rate of pulmonary hypertension in Korea” at its ninth Congress and fourth East Asian Society of Pulmonary Hypertension Congress (PH Korea 2024 with 4th EASOPH) at Dragon City in Seoul.

Dr. Kim Dae-hee, the society’s policy director who is also a professor of cardiology and head of the Pulmonary Hypertension and Venous Thrombosis Center at Asan Medical Center, presented “Policies to Overcome Pulmonary Hypertension in Korea,” urging the government to support the introduction of new medications, health insurance benefits, and the establishment of specialized centers.

According to the society, pulmonary arterial hypertension is a fatal condition in which the space inside the pulmonary artery vessels shrinks and pulmonary vascular resistance gradually increases, resulting in increased right ventricular afterload and a high likelihood of right ventricular failure and premature death. Pulmonary hypertension is defined as pressure on the right heart exceeding 20 mmHg, and when pulmonary hypertension is divided into groups 1 to 5, pulmonary arterial hypertension is group 1. It accounts for 3 percent of pulmonary hypertension.

Pulmonary arterial hypertension used to be a cancer-like disease with a five-year survival rate of only 34 percent in the 1980s. Still, survival rates have improved with the development and advancement of many drugs. According to data from the National Health Insurance Service, the five-year survival rate in Korea was expected to be 72 percent in 2023.

Previously, calcium channel blockers, diuretics, anticoagulants, and oxygen therapy were used to treat pulmonary arterial hypertension. However, recent developments have introduced endothelin pathway targeting drugs (ambrisentan, bosentan, and macitentan), PDE5 inhibitors (sildenafil, tadalafil, and riociguat), prostacyclin pathway targeting agents (celexipag, epoprostenol, treprostinil, iloprost, and beraprost), and two- or three-drug regimens combining these agents.

“Global guidelines call for combination therapy from the outset, but Korea still allows only sequential combination therapy,” Professor Kim said. “Especially in high-risk patients, initial three-drug combination therapy is not possible, and insurance coverage for initial combination therapy has yet to be recognized.”

As the health insurance does not support the initial combination, physicians add one agent with a different mechanism of action if there is insufficient clinical response after more than three months of treatment.

“Epoprostenol, an intravenous prostacyclin pathway targeting drug said to be the most effective, has not yet been introduced in Korea, and tadalafil, which is the most popular drug, is not even approved by the MFDS, only sildenafil is now available among PDE5 inhibitors,” Kim pointed out. “If these drugs can be introduced and used in Korea, it will change the game for pulmonary arterial hypertension treatment options, which have been limited to symptom control.”

According to Kim, government support is even poorer for chronic thromboembolic pulmonary hypertension (CTEPH), which is group 4 pulmonary hypertension. CTEPH is so rare that only 174 people have been diagnosed with it. However, CTEPH doesn't even have a disease code yet, so it can't be properly counted, and it's not designated as a rare disease, meaning it doesn't qualify for any special calculation benefits.

Therefore, the society will make policy proposals to the government to calculate a disease code for CTEPH and reduce the burden of medical expenses by designating it as a rare disease subject to special calculation benefits.

Dr. Kim also pointed to the unmet need for pulmonary arterial hypertension.

“Although the five-year survival rate of patients with pulmonary arterial hypertension has increased, it is still lower than in Japan, where it is over 90 percent,” he noted. “We need to raise the disease’s awareness and increase its early diagnosis rates. To do this, we need specialized centers for pulmonary arterial hypertension.”

The survival rate of patients with pulmonary arterial hypertension is dramatically different, depending on the presence or absence of a specialized center. According to Kim, there are 80 pulmonary hypertension centers in the United States, more than 50 in Australia, and 17 in Canada.

“In Korea, it is difficult to find a hospital with a multidisciplinary team, let alone a specialized pulmonary hypertension prescription center,” Kim said. “The government's attention is urgently needed.”

The society plans to identify hidden patients through early diagnosis and improved disease awareness.

According to Dr. Kim Kyung-hee, a professor of the Department of Cardiology at Sejong General Hospital and the society’s public relations director, there are an estimated 4,500 to 6,000 patients with pulmonary arterial hypertension in Korea. However, only about 1,500 patients are being treated in Korea.

“Pulmonary arterial hypertension is a unique and newly recognized disease group that includes a variety of cardiovascular diseases and rare diseases within pulmonary hypertension, and even doctors still have difficulty diagnosing and differentiating pulmonary hypertension from pulmonary arterial hypertension,” Kim said. “The prognosis is very good if early diagnosis is made and appropriate treatment is provided quickly.”

In response, the society is launching the “Lung, Family, and Hope Campaign” to raise awareness of pulmonary hypertension. In addition to developing and distributing educational materials on diagnosing and treating pulmonary hypertension for medical professionals, the society is also producing and distributing educational videos to help patients understand the symptoms of pulmonary hypertension and visit the right hospital.

“We will continue our campaigns to provide accurate information about the disease,” the PR director added.

Chung Wook-jin, the society’s president and a professor of cardiology at Gachon University College of Medicine, proposed the “Project to Overcome Pulmonary Hypertension Utilizing Whole-Cycle Precision Medicine (OPUS-K)” to the government to overcome the intractable disease, which is the society’s mid- to long-term project that aims to raise the compliance rate of pulmonary hypertension guidelines in Korea to the level of developed countries and increase the survival rate of pulmonary hypertension in Korea to the highest in the world.

“In detail, the OPUS-K project will carry out four tasks: translational research to discover diagnostic biomarkers and therapeutic targets, the establishment of an international cooperation system for precision medicine, randomized clinical research to generate evidence, and implementation research to improve guideline compliance,” Chung explained. “Through this project, we expect to improve the five-year survival rate of intractable pulmonary hypertension, which has lagged behind developed countries such as the United States, the United Kingdom, and Japan, by more than 95 percent, especially in patients with pulmonary arterial hypertension, by 10 percent.”

Chung continued, “Our society's motto is ‘As long as you breathe, there is hope.’ We still fall short of world-class standards, with survival rates of more than 70 percent when diagnosed early. So, continued government support for early diagnosis and increased expertise in treatment and management is essential.”