Pulmonary embolism (blood clots in the pulmonary circulation)
Pulmonary embolism occurs when a blood clot, usually from the leg, travels to the lungs and blocks a blood vessel. Pulmonary embolism can increase the risk of right heart failure, a condition where the right side of the heart is unable to pump blood effectively. Pulmonary embolism can lead to an increase in pressure in the pulmonary arteries, which can put a strain on the right ventricle of the heart. If this pressure is sustained over time, it can lead to the enlargement of the right ventricle and eventually, right heart failure. The risk of right heart failure is higher in patients with larger clots or multiple clots, those with pre-existing heart or lung disease, and those who experience recurrent pulmonary embolism. Symptoms of right heart failure may include shortness of breath, fatigue, and swelling in the legs. Early diagnosis and treatment of PE are important in reducing the risk of right heart failure. Treatment options may include anticoagulant therapy, thrombolytic therapy, and in severe cases, surgery. Intermediate to high-risk pulmonary embolism can lead to acute pulmonary hypertension due to an increase in pulmonary vascular resistance, which is partly caused by pulmonary vasoconstriction. This results in an increased workload on the right side of the heart, leading to right heart failure and even death in severe cases.
There is still an unmet medical need for the treatment of acute pulmonary hypertension to prevent right heart failure in intermediate to high-risk pulmonary embolism. While several treatments are available to reduce pulmonary vascular resistance and improve right ventricular function, there are still limitations and challenges in their use. For example, while thrombolytic therapy can improve outcomes in intermediate to high-risk pulmonary embolism, it carries a risk of bleeding and is not suitable for all patients. Moreover, the use of pulmonary vasodilators like inhaled nitric oxide and prostacyclin can also be limited by their potential side effects, such as hypotension and rebound pulmonary hypertension. Thus, there is a need for novel therapies that can effectively reduce pulmonary vascular resistance and prevent right heart failure in patients with intermediate to high-risk pulmonary embolism while minimizing the risk of adverse events. Attgeno are exploring Supernitro as selective pulmonary vasodilator, to address this unmet medical need and clinical trials are necessary to evaluate the safety and efficacy of this novel therapy in treating acute pulmonary hypertension in intermediate to high-risk pulmonary embolism.
The incidence of intermediate to high-risk pulmonary embolism in the United States is not precisely known. However, it is estimated that PE affects approximately 300,000 to 600,000 people in the US each year, with about 60,000 to 100,000 deaths annually attributed to this condition. The incidence of intermediate to high-risk pulmonary embolism PE specifically depends on the population studied and the diagnostic criteria used. Studies show that 15-25% of cases with acute pulmonary embolism are classified as intermediate to high risk based on clinical and imaging criteria. Accordingly, the incidence of intermediate to high-risk pulmonary embolism in Europe is not precisely known, and it can vary depending on the country, the population studied, and the diagnostic criteria used. However, it is estimated that pulmonary embolism affects approximately 1 to 2 per 1,000 individuals in the general population of Europe, with a higher incidence among hospitalized patients. Among patients with acute pulmonary embolism, about 25% to 30% are classified as intermediate to high risk based on clinical and imaging criteria. It’s important to note that these estimates are based on studies that may not capture all cases of pulmonary embolism, and the actual incidence of intermediate to high-risk pulmonary embolism may be higher or lower than these estimates.
Animal studies have shown that Supernitro can effectively reduce pulmonary vascular resistance and improve right ventricular function in models of acute pulmonary hypertension induced by pulmonary embolism. While the preclinical data on Supernitro is promising, further studies are needed to evaluate its safety and efficacy in treating acute pulmonary hypertension in humans with intermediate to high-risk pulmonary embolism.