Disappointing Results from mRNA-based Cystic Fibrosis Therapy

Disappointing Results from mRNA-based Cystic Fibrosis Therapy

Those monitoring progress in cystic fibrosis therapies were disappointed Wednesday when a messenger RNA-based biotech company called Translate Bio shared trial data that although safe, the novel therapy failed to work well. Of course, the news didn’t help the Boston area biotech firm’s stock price (TBIO). Known as MRT5005, this investigational product is an inhaled mRNA-based treatment developed to apply to cystic fibrosis. The investigational product is designed to utilize the patient’s own cells to produce a specific protein known as CFTR that they are not able to produce due to the disease. In 2019, the company did share data generated from the same trial implying that the drug actually had a positive impact on lung function after one dose. However, after the multiple dose segment of the trial, any positive indicators were gone. While Ron Renaud, CEO, commented that this trial lacked power for efficacy he indicated that no big conclusions can be drawn from these data points.

The Condition

Cystic fibrosis is the most common fatal inherited disease in the United States, affecting more than 30,000 patients in the U.S. and more than 70,000 patients worldwide. CF is caused by genetic mutations that result in dysfunctional or absent CFTR protein. This defect causes mucus buildup in the lungs, pancreas and other organs. Mortality is primarily driven by a progressive decline in lung function. According to the Cystic Fibrosis Foundation, the median age at death for patients with CF was 32.4 years in 2019. There is no cure for CF. Currently marketed, CFTR modulators are effective only in patients with specific mutations, and patients still experience pulmonary exacerbations and a progressive decline in lung function, which represents a significant unmet need.

mRNA Evolution

Importantly this investigational therapy was one of the first such therapies developed and since the onset of the pandemic and the Moderna and BioNTech mRNA-based vaccine candidates authorized under emergency use—with over 70 million Americans inoculated with at least one dose—this life science-based technology has advanced considerably.

The Study

A small Phase 1/2, 14 patient clinical trial yielded thus far from multiple ascending dose portions represents the first inhuman study to deliver multiple doses of mRNA-based therapy delivered to the chronically ill over the long run. The company reported no serious adverse events based on multiple ascending dose segments of the clinical trial.

The randomized, double-blind, placebo-controlled Phase 1/2 clinical trial of MRT5005 is designed to enroll at least 40 adult patients with CF who have two Class I and/or Class II mutations. The primary endpoint of the trial is safety and tolerability of single and multiple escalating doses of MRT5005 administered by nebulization. Percent predicted forced expiratory volume in one second (ppFEV1) is also measured at predefined time points throughout the trial. The Phase 1/2 clinical trial of MRT5005 for the treatment of CF is being conducted in collaboration with the Cystic Fibrosis Foundation Therapeutics Development Network and the Emily’s Entourage Patient Registry. For more information about the Phase 1/2 clinical trial, visit here.

CEO on the Record

Mr. Renaud went on the record, “This is the first time messenger RNA encoding CFTR has been administered to patients with cystic fibrosis through inhaled repeat doses, and I believe, this represents an important building block in our pioneering efforts to develop transformative mRNA therapeutics.”

Hope to the Future

“We have seen the impact that mRNA is having across the vaccine landscape, and given the novelty of its science, I am hopeful that mRNA may have a similar role in treating pulmonary diseases including cystic fibrosis,” said Steven Rowe, M.D., director of the Gregory Fleming James Cystic Fibrosis Center, professor in the Division of Pulmonary, Allergy and Critical Medicine at University of Alabama, Birmingham, and principal investigator of the Phase 1/2 clinical trial of MRT5005. “While innovative clinical science is often incremental, I believe that with these interim results we have gleaned important insights applicable to mRNA therapeutic development for cystic fibrosis.”


The company’s opportunity has expanded thanks to the pandemic as it was selected by Sanofi to enter into a Phase 1/2  trial, which purportedly will generate data that can be reviewed later in the year.

Call to ActionTrialSite doubts the company’s prospects for a compelling cystic fibrosis treatment in the short to intermediate run.