A breath of fresh air for patients with pulmonary arterial hypertension

What is PAH?

Pulmonary Arterial Hypertension (PAH) is a progressive disease in which obstruction and progressive remodeling in the small arteries result in abnormally high blood pressure in the lung vasculature. This impedes blood flow through the lungs, causing the heart to work harder and eventually, over time, to lose the ability to effectively pump blood throughout the body as the right ventricle (RV) enlarges.¹ Symptoms can include shortness of breath, fatigue and chest pain, and can resemble those of heart failure.² Diagnosing PAH can be challenging, requiring extensive testing that can include:

• Blood tests
• Electrocardiogram
• Lung function tests
• Echocardiogram
• Right heart catheterization³

On average, it can take more than two years to arrive at an accurate diagnosis for PAH due to complexity of disease and subtlety of symptoms.⁴

PAH is one of five groups of pulmonary hypertension (PH) defined by the World Health Organization:

• Group 1: Pulmonary arterial hypertension
• Group 2: Pulmonary hypertension due to left heart disease
• Group 3: Pulmonary hypertension due to lung disease
• Group 4: Pulmonary hypertension due to chronic blood clots in the lungs.
• Group 5: Pulmonary hypertension due to unknown causes⁵

Group 1 PAH accounts for only three percent of total PH cases.⁶

How prevalent is PAH?

PAH is a rare condition. Only five hundred to a thousand new cases are diagnosed in the United States each year. The current total number of people currently living with PAH is estimated at 10,000 to 20,000. Although its cause is frequently unknown, the American Lung Association estimates that 15 to 20 percent of patients inherit the condition. PAH patients are predominantly female - estimates gleaned from registries range from 56 to 86 percent.⁷ Eventual heart failure can lead to premature death.⁸ However, with earlier diagnosis, increased specialization and improved treatments, median survival rates have risen over the past several years. The prognosis for women is better than it is for men, giving rise to a phenomenon known as the "estrogen paradox."^9,10

How is PAH treated?

Fortunately, many PAH-specific therapies have been developed. Patients are often on multiple therapies to manage their PAH, including oral, subcutaneous (SC), infused and inhaled drugs: 46 percent are on dual and 9 percent are on triple therapy.¹¹

Oral treatment options include:

• Endothelin Receptor Antagonists, which help prevent blood vessels from narrowing
• Phosphodiesterase Inhibitors and Soluble Guanylate Cyclase Stimulators, which allow the lungs to produce more of their own natural vasodilators and relax the blood vessels in the lungs
• Prostacyclin Analogue and Selective IP Receptor Agonists, which help the blood vessels in the lungs to relax

Prostacyclin analogues are available in both inhaled and subcutaneous and IV routes, to help improve symptoms of PAH. Selection of route of administration is patient specific including both prescriber and patient input.

Oral

Adcirca (tadalafil), Adempas (riociguat), Alyq (tadalafil), Letairis (ambrisentan), Opsumit (macintentan), Orenitram (oral Treprostinil), Revatio (sildenafil), Tracleer (bosentan), Uptravi (selexipag)

Infused

Flolan (epoprostenol), Veletri (epoprostenol), Remodulin (treprostinil), Uptravi (selexipag)

Inhaled

Tyvaso (inhaled Treprostinil), Ventavis (iloprost)

PAH patients are taught to be independent with their SC administration or IV infusions. Nurses initially conduct intensive training with these patients, teaching them to mix and administer their continuous infusions or inhaled therapies.

Treatments also can include calcium channel blockers, oxygen and blood thinners.¹²

PAH is a progressive disease. While there is no cure, advancements in treatment can reduce the severity of symptoms and have increased life expectancy for patients with PAH. Whereas median survival from time of diagnosis was 2.5 years, many patients now are living three to four times as long.¹³

What are the upcoming notable drugs for PAH in the pipeline?

A new dry powder inhalation formulation of Tyvaso (treprostinil) by United Therapeutics/MannKind is pending approval for the treatment of PAH and pulmonary hypertension associated with interstitial lung disease. It's is anticipated to launch in 2022.

A dry powder inhalation formulation of Yutrepia (treprostinil) by Liquidia Technologies is pending full FDA approval for the treatment of PAH. It's is expected to launch in the fourth quarter of 2022.

These products would be used as more portable alternatives to nebulized Tyvaso and are likely to compete for market share.

United Therapeutics is in late-stage development of Tyvaso (treprostinil) nebulization formula for a supplemental indication to treat pulmonary hypertension due to COPD (WHO Group 3). It is currently approved for PAH (WHO Group 1) and pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3). It would be the first FDA-approved therapy for pulmonary hypertension due to COPD and is anticipated to launch in late 2023.