New Treatment for Lung Transplant Recipients Experiencing Chronic Rejection
By Ella Balasa
Lung transplantation brings much hope to individuals battling severe lung disease with cystic fibrosis. However, long term prognosis is variable due primarily to the possible development of chronic rejection. The medical term for this is “bronchiolitis obliterans syndrome”, or BOS. Nearly 50% of patients develop BOS within 5 years following lung transplant. BOS is a lung disease where the immune system attacks the airways causing inflammation that leads to scarring and blockage of the small airways. BOS is diagnosed by a decline in FEV1 or by lung biopsy.
What’s being done about it?
Breath Therapeutics is a small company founded in 2016 that is currently developing a drug being studied to treat BOS. It is a formulation of cyclosporine that is inhaled through a nebulizer and delivered directly to the lungs. This treatment is called L-CsA-i. It stands for Liposomal Cyclosporine A for inhalation. It is administered through the eFlow® Nebulizer System (PARI Pharma), designed for home-inhalation. Unlike other immunosuppression drugs on the market, the inhaled approach allows L-CsA-i to be delivered directly to the lung.
What have Breath Therapeutics research and clinical trial results yielded so far and what will be the upcoming trial’s goals?
In a previous single-center study, 82% of those patients that were on L-CsA plus their standard treatment regimen had no BOS progression while only 50% of those using only their standard treatments had no BOS development. In addition, FEV1 stabilized for patients on the study drug but worsened for those not taking it. Prior studies have indicated good tolerability of the inhaled treatment without systemic toxicity, which led the way to the global phase three studies now underway.
The drug is currently being tested in phase three trials in adult lung transplant recipients. The study, known as BOSTON-2, examines the safety and effectiveness of L-CsA-i to treat BOS in patients who have received a double lung transplant.
Participants will be randomized to either be given the study medicine in addition to their normal treatments or only receive their usual treatment without the addition of the study drug. Both groups will have 55 patients enrolled.
There will also be an open-label extension study called BOSTON-3 in which all patients will add the trial drug to their medication regimen. But, only patients who complete BOSTON-2 can enroll in the BOSTON-3 study, if they are eligible. The study will follow patients for up to 3 years.
Do you think you qualify and are interested in participating?
The study is being conducted at roughly 35 hospitals in the United States and Europe. They are currently recruiting individuals with BOS. Individuals are encouraged to discuss these studies with their transplant doctors or research coordinators to see if they might qualify.
If your transplant center is not a study site, you can participate if your physician refers you to an active study site! All participating centers and contact info are listed on the Clincaltrials.gov site.
What can be expected from this treatment in the coming years?
Although this is dependent on the success of the drug in trials, in April, the FDA granted Fast Track designation to Liposomal Cyclosporine A for Inhalation (L-CsA-i). The Fast Track status would allow this treatment to become available more quickly if criteria in trials are met. This means it could also receive Accelerated Approval and Priority Review at the time of a New Drug Application (NDA) filing.
Roberto Tascione, the CEO of Zambon says, “Zambon is committed to its mission of innovating a cure and improving the quality of life for people living with severe respiratory diseases worldwide. The FDA’s Fast Track designation for L-CsA-i represents an important recognition of its potential to address the unmet medical need of patients with BOS, a devastating rare disease with currently no approved treatment.”
Still have questions or need info? If you have any other questions regarding the BOSTON studies, send them via email to firstname.lastname@example.org and visit this Breath Therapeutics site for more FAQs.
About the Author: Ella is a director for USACFA. She is 28 years old and was diagnosed with CF at 18 months old. She has a B.S. in biology and has worked in an environmental microbiology lab. She serves on various research committees, planning virtual events, and writes to provide a scientific voice and encourage empowerment to the CF community as well as introspectively writing about the hardship yet triumph that comes along with a chronic disease. When she is not taking care of her health, she enjoys cooking, drawing, and spending time with friends. Follow her life experiences on Instagram @thisgirlella.