Exclusive: Breath Therapeutics Launches Phase III Trial to Bring Relief to BOS Patients
In five years it is estimated that about 30,000 people in the United States, Europe and Japan will develop bronchiolitis obliterans syndrome (BOS), which results in respiratory failure and death. But a late-stage treatment under development by Breath Therapeutics could be a possible remedy for this rare and dread disease.
Breath Therapeutics Chief Executive Officer Jens Stegemann called BOS a devastating disease among lung transplant patients for which there is currently no cure. For these patients, he likened BOS to a severe cancer diagnosis, which he said makes a treatment for BOS a severe unmet need. However, Germany-based Breath Therapeutics initiated two Phase III trials attempting to repurpose an old drug to help these lung transplant patients.
“We’re teaching an old dog new tricks,” Stegemann said of Breath’s proprietary liposomal formulation of cyclosporine A. He added that the company’s inhaled cyclosporine therapeutic may provide the first safe and effective treatment for BOS.
The company has developed the medication to be administered to patients via a drug-specific investigational eFlow nebulizer developed by the parent company of Breath, PARI Pharma. Breath launched in 2017 as a spinout of PARI Pharma, which is based in Munich. L‑CsA‑i has received orphan drug designation for the treatment of BOS from the Food and Drug Administration and European Medicines Agency.
BOS occurs when the body’s immune system attacks the small airways of the transplanted lungs and destroys the bronchioles. BOS is caused by T-cell mediated inflammation that leads to blockage of bronchioles. There are more than 30,000 lung transplantation and allogeneic hematopoietic stem cell transplantation recipients worldwide currently affected by BOS. Stegemann told BioSpace that approximately 50 percent of lung transplant patients will be affected by BOS. The immune response to the transplant is one of the main reasons why lung transplants have the poorest outcomes, Stegemann said.
“Although lung transplant survival has improved with the advancement of surgical techniques and perioperative management, and more individuals are undergoing lung transplantation, survival has not improved to reach the rate of other organ transplantations. One key factor impacting survival in lung recipients is rejection, particularly bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction,” Joseph M. Pilewski, the associate chief for clinical affairs and lung transplant physician in the Division of Pulmonary, Allergy & Critical Care Medicine at the University of Pittsburgh Medical Center, said in a statement supplied to BioSpace.
The drug at the core of Breath’s therapy was initially introduced in the 1980s to benefit organ transplant patients. However, Stegemann said there were some toxicity issues associated with the medication. However, due to the inhaled formulation of cyclosporine A that Breath has developed, high amounts of the immunosuppressant drugs can be directly delivered into the lungs, which lowers concerns about toxicity.
Breath launched two Phase III trials, the BOSTON-1 trial for individuals with BOS following a single lung transplant and BOSTON-2, for double lung transplant patients. Each study will enroll 110 participants at leading lung transplant specialty centers in eight countries. When the 48-week studies are complete, the patients will be eligible to continue in the planned BOSTON-3, an open-label extension trial.
Stegemann said the launch of the two Phase III trials represents a major milestone for the two-year-old company. He said it is “indicative of the outstanding progress we Breath Therapeutics) have achieved in the past 24 months.” As they move into the trials, Stegemann said the company is “well positioned to succeed in our goal of bringing an effective and safe treatment to people with BOS.”
Data from the BOSTON 1 and BOSTON 2 trials are expected in 2021. Stegemann said in Europe and the U.S., Breath will also plan to conduct pediatric trials in BOS.