Adempas Safely Treats BPD and PH in Newborns Without Affecting Bone Growth, Rat Study Reports

Adempas (riociguat), an approved therapy for adults with pulmonary hypertension (PH), may hold promise for treating newborns with bronchopulmonary dysplasia (BPD) and PH, results of an animal study show.

These findings suggest that Adempas’ use in babies is safe and beneficial — and does not cause bone growth defects, a concern that has kept doctors from considering the medicine in newborns to date.

The study, “Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth,” was published in the journal PLOS One.

BPD is a serious lung condition that primarily affects premature infants. The condition develops as a result of the infant’s lungs becoming irritated or inflamed due to oxygen ventilation or infection (inhaled nitric oxide is a common BPD treatment). Disease burden is particularly high for preterm babies who weight less than 2 pounds (about 1,000 grams), with 40 percent of these babies developing the condition.

BPD prognosis can be further aggravated by the co-occurrence of PH, which can arise as a complication of BDP. A premature baby with both diseases has a 50 percent chance of surviving.

So far, no effective therapies exist prevent or treat BPD associated with PH, and available PH medications are not approved for use in newborns.

Adempas, marketed by Bayer, was approved by the U.S. Food and Drug Administration (FDA) to treat pulmonary arterial hypertension symptoms in adults in 2013. Adempas works by stimulating an enzyme called soluble guanylate cyclase, which leads to relaxation of arterial muscle walls. As a result, the arteries widen (vasodilate), blood circulates more freely to lower blood pressure, and oxygen gets better distributed throughout the body.

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The medicine offers benefits over inhaled nitric oxide (a known vasodilator) and may be particularly beneficial in a BPD setting, in which lungs might get injured due to excessive exposure to oxygen, causing oxidative stress.

However, Adempas is not approved for use in newborns, or older babies and children, due to concerns that it may disturb bone growth — studies in rats have shown that soluble guanylate cyclase stimulators can induce bone resorption, remodeling, and new bone formation.  

To address this concern, researchers evaluated the efficacy and toxicity of Adempas in neonatal rats that model BPD and PH. Their study assessed the therapy’s efficacy in preventing lung injury, and its potential effects on long bone growth in newborn animals.

To induce BPD and PH-like symptoms, newborn rats were exposed to high oxygen concentrations (85% oxygen), or hyperoxia, within 24 hours of birth. The animals were then divided into two groups: one injected with Adempas and the other with a placebo, once daily for nine days.

Treatment with Adempas significantly decreased lung inflammation, and recovered the development of alveoli — the small cavities rich in blood vessels through which gas exchanges occur in the lungs.

Treatment also restored blood vessel development in the animals’ lungs to levels closer to normal.

Adempas also worked to reduce PH, lowering the heart’s right ventricular systolic pressure (RVSP) — a measure of the pressure in the artery that supplies blood to the lungs.

Importantly, Adempas had no significant effect on the growth and formation of long bones, as assessed by measurements of the tibia — the main bone of the leg that forms the shin. Bone structure, measured by CT scans, also showed no adverse changes in animals treated with Adempas.

“These data indicate that riociguat is beneficial in preventing hyperoxia-induced lung injury and PH without affecting long bone growth and structure and hence, suggests riociguat may be a potential novel agent for preventing BPD and PH in neonates,” the researchers wrote.