Pleural effusion (PE) doesn’t begin as a life-threatening illness, but may arise as a severe complication of pneumonia. Pneumonia is characterized by fluid in the lungs due to an infection, and most often is treatable with antibiotics. But sometimes…
In severe cases of pneumonia, fluid begins to build up in the space between the lungs and the lung lining, a space called the pleural cavity. This defines the condition called pleural effusion. In even more severe cases, the pleural fluid itself becomes infected, a condition called empyema.
Fluid in the pleural cavity prevents full expansion of the lungs making it difficult to breathe, and the fluid is typically removed using drainage tubes. However, in some cases fibrotic scar tissue may also build up, trapping the fluid in pockets thus preventing drainage. This condition is called loculated pleural effusion.
When locutaion prevents fluid drainage, the standard of care is surgery to remove the scar tissue. Surgery itself presents a number of risks to the patient, including bleeding and infection, and many patients may not be strong enough to undergo surgery.
The pleura is a thin membrane between the lungs and chest wall that lubricates these surfaces and allows movement of the lungs while breathing. Pleural effusion is when fluid fills this gap and separates the lungs from the chest wall. The condition is more serious when the fluid itself becomes infected (called complicated parapneumonic effusion (CPE), or empyema). Fibrotic scar tissue may form in the pleural cavity (called loculation), preventing effective drainage of the fluid. If the fluid cannot be drained, the lungs aren’t able to expand and oxygenate the blood sufficiently.
Numerous medical conditions can cause pleural effusion. Some of the more common causes are:
Surgery has risks
When loculation prevents fluid drainage, the standard of care is surgical procedure to remove the scar tissue. Surgery itself represents a number of risks to the patient, including bleeding, iatronic infection, persistent chest pain and other risks. In addition, many patients are not operative candidates, having significant co-morbidities that often accompany patients hospitalized with pneumonia.
Off-label drugs are not consistently effective
Some physicians have tried using fibrinolytic ‘clot busting’ drugs approved for other disease conditions to break up scar tissue and improve drainage. These drugs are not approved by the FDA for resolving CPE/empyema, and have not been optimized for dosing these patients. Clinical results for this off-label pharmaceutical route have been highly inconsistent.
LTI-01 is our lead compound for loculated pleural effusions. The product has undergone significant research and pre-clinical development under several NIH grants and programs totaling more than $17 million in funding. LTI-01 is the first pharmaceutical agent to enter into clinical trials for treating non-draining CPE/empyema. A Phase 1b clinical trial is being conducted at three sites each in Australia and New Zealand. LTI-01 is a proenzyme, or zymogen, becoming activated in the pleural space.