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Research Corner: MRT5005 – A Novel Therapy for Treating CF

Updated: Feb 8, 2020

By Ella Balasa

The interim results from an ongoing Phase 1/2 clinical trial of an RNA therapy which is showing the potential to benefit everyone with cystic fibrosis regardless of mutation, circulated in the CF community about two weeks ago. For those with CF who currently have no modulator therapies available to them, the positive results which showed an increase in lung function after just one dose is exciting news! But before I dive into the study details, I’ll explain a bit of background on what exactly this therapy does. My many faint recollections of cell biology class from upwards of six years ago will help me explain in laymen’s terms.

So how does this therapy mechanism work? The RNA piece that is used to create the fully-functioning CFTR protein in CF lung epithelial cells is introduced by inhalation through a nebulizer. Specifically, it is the Innospire Go nebulizer. (If you need a refresher course on the CFTR protein, follow the links to get the basics first.) This RNA piece is encapsulated in a lipid (fat) layer so that it doesn’t degrade before entering the cell. The lipid layer also helps to penetrate the mucus layers. Those with CF without any science background, I’m sure, can agree that mucus isn’t an easy substance for things to pass through - like molecules of oxygen when we breathe for example. So, to successfully penetrate this layer is a pretty big feat for scientists! Then, once the lipid capsule gets into cell, it opens up allowing the RNA to start getting to work in the ribosome to produce the CFTR proteins, correcting the improper chloride and water ratios in our lungs. The way in which this differs from modulator therapies is that this method provides the full coding for the CFTR protein to be made, no matter which mutations of the gene you have. Modulators, on the other hand, help some of the deformed and defective, but existing, CFTR proteins in our cells to function properly.

“By addressing the central step in the production of proteins, our MRT product candidates are designed to give the body the instructions to make its own therapeutic protein” – Translate Bio

Now, I’ll get to some of the findings of MRT5005 and what the researchers are analyzing next. The interim results showed that only one dose improved lung function by an average of 15.7% FEV1 after just 8 days for the 16mg dose group. Of the 12 patients in the study, 1 patient had mutations that were not amendable with any current modulator therapies, yet still showed an improvement in FEV1 in this study. Importantly, as safety and tolerability is the key aspect of these early phase studies, no serious adverse events were documented at any of the three dose levels.

Future parts of the planned studies will examine multiple doses at varying concentrations. The doses will be administered by inhalation once a week for 5 weeks in certain cohorts. This dosing frequency has been determined from the data that indicated the potential for peak CFTR production to be between the 2-3 day mark, and that by day 8, FEV1 started to trend down. RNA is easily degraded, and the created proteins from the introduced RNA also degrade over time. Since this is not gene therapy, the RNA needs to be continually reintroduced into the cells to maintain a sufficient presence. The various dose concentrations will be used to determine the optimal dose to get the maximum benefit with the least possibility for adverse events.

How can you be a participant in trials? If you are interested in participating in clinical trials, there are opportunities to enroll in ongoing studies at 15 centers across the US. Future phase 2 trials will include many more sites in Europe. For more information visit Take a look at the list of clinical sites, and I encourage you to contact the clinical point of contact that is listed on the page. Keep in mind, however, that if you have lung function below 40% you wouldn’t be able to participate in trials. The unfortunate reality is that, as with most trials for CF, this is the inclusion criteria cutoff for FEV1 that has been determined to have marked improvement in clinical trial endpoints.

I recently had a chance to ask Dr. Barbier, Chief Medical Officer of Translate Bio,

a few questions about her thoughts on the future of mRNA therapy for people with CF. I asked whether mRNA therapy could become a primary form of treatment for CF to benefit every single person with this disease. Her answer was matter of fact. “Absolutely.” Efficacy and safety of the treatment will be the drivers of it becoming a part of the new era of CF care that is increasingly showing signs of slowing the progression of the disease over time. It may come down to preference for patients, whether they would rather take daily pills, which are the method of delivery for some of the therapies this treatment parallels with, or inhaled as this regiment would be.

How quickly could we see this treatment come to market? The standard for treatments to complete clinical trial stages and get to market so far for CF has been about 5 years. As news of this therapy becomes more known in the community, enrollment into studies will proceed faster. This makes a tremendous difference in timeline. The fact that this treatment could potentially be one of the first to treat the roughly 10% of those with rare mutations who have no modulator treatments available to them, may engender flexibility with regulators and compress timelines.

As someone who is hopeful to soon benefit from a modulator therapy myself for the first time - specifically the triple combination - I can understand the feeling of running out of time for new treatments to become available. But I believe this treatment is adding that glimmer of hope quickly for those that currently have no treatments on the horizon.


About the author:

Ella is a director for USACFA. She is 27 years old and was born and raised in Richmond, Virginia. She was diagnosed with cystic fibrosis at 18 months old. She has a B.S. in biology and has worked in an environmental microbiology lab.

Becoming more involved within the CF community, she has received much joy from both gaining and giving support to others that face similar challenges. Her involvement in the CF community has expanded through serving on various research committees, planning virtual events, and writing to provide a scientific voice and encourage empowerment to the CF community as well as introspectively writing about the increasing hardship yet countless triumphs that come along with living a life with a chronic disease. When she is not taking care of her health, she enjoys cooking, drawing, spending time with friends, and traveling as much as she can. Follow her life experiences on Instagram @thisgirlella.

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