Top 10 for 2021: #4 | New Medication for Cystic Fibrosis

Top 10 for 2021: #4 | New Medication for Cystic Fibrosis

Passing a hereditary disease to a child is one of a parent's worst fears. Although uncontrollable, one in every 35 Americans, is born with a defective cystic fibrosis, or CF, gene. With CF, mutations in the cystic fibrosis transmembrane conductance regulator, or CFTR gene, cause the CFTR protein to become dysfunctional, making it unable to help move chloride to the surface of the cells in the body. Without the chloride to attract water to the surface, the mucus in various organs becomes thick and sticky, causing it to clog the airways and trap germs, leading to infections, inflammation, respiratory failure, and other complications.

But there's a new combination drug to help the CFTR protein work, effectively thinning mucus. FDA approved in October 2019, the medication can be used in patients with the most common CF gene mutation, F508del. An estimated 90% of individuals living with CF in the United States have at least one copy of F508del, and no medication to date has been applicable to such a large group of individuals living with CF. Clinical trial results show the medication increased patient's forced expiratory volume in one second (FEV1), an established marker of CF lung disease progression, by nearly 14%. This advancement in specialized CF care has the potential to add years and quality of life for many living with the condition.

Akhil Saklecha, MD:
Hi, this is Akhil Saklecha from Cleveland Clinic Ventures. We're going to be talking about #4 on our Top 10 Medical Innovations List, ‘New Medication for Cystic Fibrosis.’ With me today is Dr. Elliott Dasenbrook, Staff Pulmonologist and Director of the Adult Cystic Fibrosis Program at Cleveland Clinic. Dr. Dasenbrook, tell us a little bit about this new class of medication for cystic fibrosis. Given what I've seen with CF, this can be a big deal, a big game-changer.

Elliott Dasenbrook, MD:
Yeah, so definitely a game-changer. This new class of medications, we call them modulators – CFTR modulators. Cystic fibrosis is a genetic disease, and the genetic mutation results in a defective protein and defective chloride channel. That's what causes cystic fibrosis. So this new class of medications, the modulators, help the protein channel function. Actually, [the channel] is misfolded as a result of the genetic mutation. So it helps correct that misfolding and moves the channel through the cell so that it can get to the membrane where it actually functions. So this new class of medications is very exciting and gets at the root cause of what's causing CF.

Akhil Saklecha, MD:
In the video we just watched, we learned that the combination drug we're talking about can improve the FEV1 by about 14% or so. Can you put that in perspective as to what that means for patients?

Elliott Dasenbrook, MD:
This is a huge impact for patients and, as a pulmonologist, I monitor patient's lung function very closely. So to have an improvement of 10 to 14% is going to translate into two things. Number one, down the line, we know that patients are going to live longer, but two, when the lung function is improving like that, we also know that they're going to feel better on a day-to-day basis.

The other thing we saw in these clinical trials was dramatic reductions in pulmonary exacerbations – that's an episode where a patient will have an acute worsening of their symptoms. You know, CF is a disease where you build up thick, sticky mucus. So when they have an acute exacerbation, these patients require two to three weeks of IV antibiotics. If you can eliminate one or two of those episodes per year for a patient, that's going to make a huge impact – not only how they feel day-to-day, but you've just freed up four to six weeks of their lives where they're feeling good and not in the hospital.

Akhil Saklecha, MD:
So how are you treating these patients now, or in the past, with cystic fibrosis, and then how are you incorporating this new treatment?

Elliott Dasenbrook, MD:
Yeah, so previous treatments with cystic fibrosis were effective, but they treated the downstream complications of CF. So we were treating infection because of the buildup of the thick, sticky mucus with something like inhaled antibiotics. Now, with this new class of medications, we're able to get at the root cause of CF, and we're really seeing dramatic improvements in their symptoms. Hopefully, that'll translate into longer life for our patients, as well. So every patient that is eligible for this therapy right now – which is about 90% of our patients – we're making sure that we can get them access to this medication.

Akhil Saklecha, MD:
You mentioned some of the improvements that patients are seeing, such as decreased hospitalization and potentially even less antibiotic treatments. In terms of their activities of daily living, what type of improvements can we see? And have there been any patients that you recall where the difference was night and day?

Elliott Dasenbrook, MD:
Yeah, so for some of our patients, I'll even make the analogy, this is like insulin for a diabetic. It's that type of improvement that we are seeing. We've had patients with more advanced stages of lung disease that were literally on the waiting list to get a lung transplant and had such dramatic improvements in their lung function and shortness of breath that they've been able to come off of the lung transplant list. That's a remarkable improvement for that individual patient. For other patients across the United States, we've seen a dramatic reduction in hospitalizations. Some CF units, where they would average 10 to 12 patients in the hospital every day, have actually closed down because there's only one or two CF patients in the hospital at a time. We're seeing lots of meaningful improvements for our patients.

Akhil Saklecha, MD:
It sounds like a real game-changer. Well, I want to thank you, Dr. Dasenbrook, for spending time with us today and telling us about #4 on our Top 10 Medical Innovations List, ‘New Medication for Cystic Fibrosis.’

Elliott Dasenbrook, MD:
Thanks for having me today – I really appreciate it.
 

To read more about #4, click here. To watch the full one-on-one interview with Drs. Saklecha and Dasenbrook, click here.

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