Study Links CF Patients’ Airway Bacteria with Disease Outcomes

By: Diogo Pinto

Researchers have linked variations in the mix of microorganisms in cystic fibrosis patients’ airways to their disease outcomes.

The findings in the journal PLOS One were in an article titled “Fluctuations in airway bacterial communities associated with clinical states and disease stages in cystic fibrosis.

CF patients typically have particular strains of bacterial and fungus in their airways. The usual bacteria suspects include PseudomonasAchromobacterBurkholderiaHaemophilusStaphylococcus, and Stenotrophomonas.

Other bacteria and fungi also inhabit CF patients’ airways, however. These include anaerobic species that do not need oxygen to grow and spread.

Not only do the microbial communities in CF patients’ airways vary by type of microorganism, but also in the relative abundance of each species.

Researchers decide to see if the prevalence and relative abundance of typical CF pathogens and anaerobic microorganisms play a role in the severity of patients’ disease and their lung function.

They analyzed 631 sputum samples collected over 10 years from 111 patients.

The team classified the stage of patients’ disease on the basis of their lung function scores. The yardstick they used was forced expiratory volume in one second, or FEV1. They considered an early stage of the disease to be an FEV1 score higher than 70, an intermediate stage a score of 40 to 70, and an advanced stage a score lower than 40.

Researchers classified disease aggressiveness — mild, moderate or severe — on the basis of change in FEV1 relative to age.

They discovered a link between variations in the prevalance of the six typical CF pathogens, plus nine anaerobic species, and changes in a patient’s disease stage and lung function.

To continue reading, click here. 

Lessons From the Road: Avoid the ER

By: Sydna Marshall

A few weeks ago I found myself in the ER at midnight in a new city.  Let me backup the story a bit. I had planned a road trip to Dallas with my bestie (we’ll call her “A” for now) for a beauty conference. Two days before the trip I ran a 102.6 fever for the better part of the day. The morning of, as I was doing my treatments and finishing my packing, I felt the familiar band of pain around my chest. I mentally ruled it out as merely remnants of pain from my blockage earlier in the week and carried on with my morning. I drove the hour north to pick up A and start our trek up to Dallas. We stopped for tacos and queso along the way. I took some pain meds for that persistent and annoying band of pain. A few hours later, we checked into our hotel, picked up our beauty boxes for the conference, and had a happy hour cocktail in the bar followed by sushi in the rotating tower.

Fast forward to 9p: CF changes on a dime. Suddenly, that pesky band of pain that I’ve absently noticed and ignored for the day is front and center. I can barely take a breath, much less a full breath, post-treatment. By 11p, I’ve laid in bed silently crying as the pain spikes up to an 8 and then back to a 6. It dawns on me that the band of pain is pleuritic pain. After texting multiple Cysters and weighing the pain with the inability to breathe, my recent 20% drop in lung functions and the fever I ran earlier, I finally make the decision to wake up A (who is for once sleeping peacefully, without interruptions, in the absence of her four kiddos) and have her drive me to the ER.

We arrive at the ER with this naïve idea that my CF clinic, albeit on-call at this late hour, will communicate with the CF clinic in Dallas. I’d already given A all of the information, phone numbers, and instructions for getting everyone, including my husband Adam, on the same page. Over the course of the evening and early morning hours, hundreds of texts and calls between A, Adam, and the on-call care team at home transpire in an effort to expedite the process.  Since it’s not my first rodeo with pleuritic pain, I’ve already determined before we even got settled in the ER that I desperately need instant-relief pain meds and a chest X-ray. Am I the only one who self-diagnoses? When you’re in and out of the doctor for the litany of health problems in addition to CF, you become the expert on your own body. I digress.

Over the course of the 12 hours in the ER, my port is accessed a total of four times, with one of them being a needle repositioning, before we get anywhere. To administer IV medication and run blood tests, two different nurses start dueling peripheral lines, one in my left hand and the other in my right elbow.  Meanwhile, other nurses attempt to get my port working, which won’t flush or draw back blood. My vein blows on one of the lines, and the other is dangerously close. I have a chest X-ray taken, a CT scan with contrast of my lungs, every blood test imaginable, an EKG, several rounds of morphine, two doses of vancomycin and two albuterol treatments.  I’m told I have a potential pulmonary embolism, a virus causing pleurisy, a mucus plug, or sepsis. Twelve hours in, and about 10 minutes after Adam arrives at the Dallas ER, my repeated requests to be moved to my home clinic, care team, and hospital are heard and I’m care-flighted from Dallas back home (Adam has to drive back home). Once admitted to my home hospital, they have me repeat nearly every test the Dallas ER did less than 24 hours prior as none of my medical records transferred with me from the ER. Five days later the medical records from the ER finally make their way to my home hospital and care team.  In the end, it was determined that I had a virus, which accounted for the difficulty in breathing, pleuritic pain, and fever. It was a very long, traumatic, stressful, and a trying 12 hours away from home. And, I missed my conference entirely, but that’s another story.

I’ve since had some time to reflect on this jaunt to the ER. The biggest takeaway for me – CF clinics do communicate but getting the ER to communicate with the CF care team is nearly impossible.  Having a port is a blessing, but it requires orders from your doctor, not just any doctor, to access and use heparin or cath flow in the event that it’s not working properly (or, in my case, repeatedly accessed incorrectly).  I learned that complaining of chest pain at a new hospital where none of my medical records are accessible means a round of tests to rule out heart problems, despite knowing that it’s my lungs. I learned that transferring medical records from one hospital to another is a royal pain in the you-know-what.

Hindsight is always 20/20, but I know I could have avoided the entire debacle if only I had heeded my inner voice the morning I left for Dallas when I first felt the band of pain around my lungs.  For me, it’s often hard to gauge when it’s important to say no and upend plans, especially when it impacts friends and family around me. If a trip to Walgreens completes a vacation in my house, am I an overachiever for my trip to the ER?

Check out Jerry Cahill’s new blog: Jerry Unplugged!

Jerry recently launched Jerry Unplugged, a new blog segment on his website where he will share insights, experiences, and more!

Who Am I?

I’m Delta F508. I’m R117H. I’m a cystic fibrosis patient. I’m post double-lung transplant by 5 years and 10 months.
I am all that and so much more. I am Jerry Cahill: athlete, coach, and friend. I have an unrivaled joie de vivre. I am positive, relentless, kind and generous. I am a man, who just happens to have cystic fibrosis. I don’t accept mediocrity. I never give up and always believe You Cannot Fail.
I was born one of six kids and, although I had CF, my parents treated me just like the others. After I was diagnosed, my mother wanted to shelter me, but my dad said, “If his life is going to be shorter, I want him to spend it with his brothers, having fun and being normal.” My dad believed that “you cannot fail as long as you try,” and I made it my life’s mantra.
I attended college and went to nationals in pole vaulting. It isn’t that I didn’t have issues because of CF, it’s just that I chose not to let them get in the way and be roadblocks. They were just detours on the way to my dreams. I went on to have a successful career while juggling the demands of CF. I never have and never will let the disease define me. The more it progressed, the more I pushed back.
Finally, nearly six years ago, at age 56, I needed a lung transplant and received one thanks to the unconditional love and generosity of a grieving family. I am grateful to my donor every day.  Continue reading…

Why I Do What I Do?

Because I can…
I believe in giving back & passing it on. I’ve been given a platform, so I use it to share what I’ve learned and experienced to benefit others. I really like the quote from the movie, The History Boys: “Pass the parcel. That’s sometimes all you can do. Take it, feel it, and pass it on. Not for me, not for you, but for someone, somewhere, one day.” I don’t do all this for myself; I do it to give hope to others, to inspire them to do more, fight harder, and be the best they can be. Everyone has limitations, but I want to inspire every person to go out and be the “hero of your own story.” Continue reading…

Doctor, Doctor!

I walked into the office the other day while Boomer was there and we began to make small talk. He asked how I was doing and I told him I had to see the doctor for my knee, because I’m having knee-replacement surgery in March. Boomer started to laugh and asked, “Just how many doctors do you have? You’re always seeing some doctor, and you act like it’s no big deal. You know, not everybody sees as many doctors as you do.”
“Boomer, I have CF! I’ve had a transplant. I have doctors but not that many, really,” I replied. Continue reading…

6 ways to get back into shape after a CF-setback

For people with cystic fibrosis, getting “back” into shape is a common occurrence. Because of the nature of the disease, patients often experience setbacks in both their health and fitness routines. But, exercise is an important and essential part of remaining compliant with treatments and medications in order to live a longer, healthier life with CF.

Continue reading 6 ways to get back into shape after a CF-setback

Clinical Trial Opportunity for Phase IV Airway Clearance System

Med Systems is sponsoring a Phase IV clinical study to measure the
effectiveness of the Electro Flo 5000 Airway Clearance System for
people who have been diagnosed with cystic fibrosis. The goal of the
study is to provide health insurers and Medicare with comprehensive
information regarding the system’s performance. The study is designed
to measure the efficacy of the system, which includes the FDA510K
(K031876) device under current indications. The study will last 30 days
and involve using the system for lung clearance and recording the
results in a digital journal. The study should take about 10 minutes per
day to record measured results in the morning after waking. You will
also be asked to use a spirometer and a digital pulse oximeter to
evaluate your lung function after using the Electro Flo 5000 Airway
Clearance System.

Interested participants must be:
 Between the ages of 18-55 years of age
 Diagnosed with cystic fibrosis
 Prescribed chest physical therapy for airway clearance
 Able to perform self-treatment- having manual dexterity
 Residing in the United States

Contact- Dr. Leigh Mack: CFtrial@mackbio.com or Phone 888-935-
8676 ext. 706

CYSTIC FIBROSIS WIND SPRINT 67: CIRCUIT TRAINING 2

For people with cystic fibrosis, getting “back” into shape is a common occurrence. Because of the nature of the disease, patients often experience set backs in both their health and fitness routines. But, exercise is an important and essential part of remaining compliant with treatments and medications in order to live a longer, healthier life with CF.  Continue reading CYSTIC FIBROSIS WIND SPRINT 67: CIRCUIT TRAINING 2

8 Tips For Protecting Your Lungs From Unhealthy Air

If you have a chronic lung condition, you’ll need to protect your lungs from being further irritated by unhealthy air. We’ve put together a list of ways to help protect your lungs against unhealthy air using information from the American Lung Association.

Check the daily air pollutant forecasts. 
There are sites on the Internet and cellphone apps where you can find out the levels of air pollution in your local area. Checking these daily can help you plan your week, helping you avoid being outside or limit your time outside when the pollution levels are high.

Try both indoor and outdoor exercise
If pollutions levels are high then avoid exercising outside. Either visit your local gym or exercise at home. Indoor shopping malls are good locations for indoor walking if you can’t go outside. Try not to exercise in places where there is a high level of traffic — traffic fumes can pollute areas up to a third of a mile away.

Reduce your carbon footprint. 
Using less electricity at home is one way to reduce your carbon footprint which helps to create healthy air for everyone. Reducing the number of car trips you make will also help. Travel by bicycle or public transport, or car share instead. Walk short distances instead of jumping in the car.

Don’t burn trash or wood. 
The ash and soot caused by the burning of wood and trash contribute to particle pollution in the atmosphere.

Don’t use gasoline-powered yard equipment. 
Gasoline-powered lawn mowers, trimmers, and leaf blowers all add to the air pollution and may irritate your lungs while carrying out your yard chores.

Encourage others to reduce their carbon footprint. 
Pressurize your local schools to run their buses according to the Clean School Bus Campaign. That means not leaving the engine running while waiting outside buildings and applying for funding for projects helping to reduce emissions.

Ask friends, family, and neighbors to reduce their energy use.

Stay away from smokers.
Don’t allow anyone to smoke in your home or place of work. Try to avoid outdoor places where people smoke cigarettes.

Be an advocate.
Be an advocate for healthier air, supporting local and national campaigns to improve the environment and reduce emissions.

Original article: https://cysticfibrosisnewstoday.com/2017/12/12/8-tips-for-protecting-your-lungs-from-unhealthy-air-2/?utm_source=Cystic+Fibrosis&utm_campaign=a772c5a83f-RSS_THURSDAY_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_b075749015-a772c5a83f-71418393

A Breath of Fresh Air for Biotechs Working on Cystic Fibrosis Therapies

Researchers from the University of Zurich have determined the structure of a chloride channel, which could be a target for new drugs to treat cystic fibrosis.

Researchers at the University of Zurich have found a new target for future cystic fibrosis treatments. The study, published in Nature, has uncovered the structure of a protein that could help to correct the mechanism underlying the buildup of sticky mucus in patients’ lungs. This could give rise to a new wave of therapeutics for the condition, which at the moment lacks disease-modifying treatments.

Cystic fibrosis is a severe genetic disease affecting the lungs, for which there is currently no cure. It is caused by a malfunctioning chloride channel, CFTR, which prevents the secretion of chloride by cells, leading to the production of thick, sticky mucus in the lung. The condition affects around 70,000 people worldwide, who suffer from chronic infections and require daily physiotherapy.

However, one potential approach to treat cystic fibrosis is to activate the calcium-activated chloride channel, TMEM16A, as an alternative route for chloride efflux. As TMEM16A is located within the same epithelium as CFTR, its activation could rehydrate the mucus layer. The research group used cryo-electron microscopy to decipher the structure of TMEM16A, which is part of a protein family that facilitates the flow of negatively charged ions or lipids across the cell membrane.

The changes that occur in the lungs of cystic fibrosis patients.

TMEM16A is found in many of our organs, playing a key role in muscle contraction and pain perception, as well as in the lungs. It forms an hourglass-shaped protein-enclosed channel, which when bound by positively charged calcium ions, opens to let chloride ions to pass through the membrane.

Current treatments for cystic fibrosis include bronchodilators, mucus thinners, antibiotics, and physiotherapy, which only control symptoms. However, biotechs around Europe are beginning to make progress, with ProQR completing a Phase Ib trial and Galapagos and Abbvie’s triple combination therapy entering Phase I. Antabio has also received €7.6M from CARB-X to develop a new antibiotic against Pseudomonas infections.

The identification of a new target provides patients and biotechs alike with renewed hope of new and effective cystic fibrosis treatments, or even a cure. It will be interesting to see whether small molecules or gene therapy specialists could take advantage of this information.

Original article: https://labiotech.eu/cystic-fibrosis-treatment-target/

An Interview: CF and Exercise

An interview with Pamela Scarborough, conducted by James Ives, MPsych

Please give an overview of the role of exercise in cystic fibrosis (CF)

We know that exercise is beneficial in helping someone to maintain their lung function, stay strong and active and maintain a good quality of life. We also know that exercise can complement ‘airway clearance techniques’ – breathing exercises prescribed by physiotherapists to help clear the lungs of mucus.

As well as benefitting lung function, exercise can help to address other complications of CF such as low bone mineral density, CF-related diabetes, low back pain, postural problems and stress incontinence.

Then, there are many other wonderful benefits such as improved mood and sleep, which is important for someone with a life-limiting condition.

Without exercise, what other methods are used to help CF patients clear the mucous that builds up in their lungs?

As physios, we use a wide range of approaches. The traditional methods that people associate with CF physio are postural drainage, percussion and active cycle breathing techniques − deep breathing exercises to open up the airways of the lungs in order to get behind sputum and get it moving so that it can be cleared with a huff or a cough.

However, we are increasingly using other techniques, for example, oscillatory devices such as a flutter or an acapella; positive expiratory pressure devices such as the Pari PEP; or different breathing exercises such as autogenic drainage. There is also a high-frequency chest wall oscillating vest, which is like a life jacket that vibrates. The aim of all physio techniques is to open up the airways, loosen the mucus, and make it easier to clear.

How important do you think physiotherapy is for people with CF? How prevalent is exercise therapy in CF treatment?

Physio is a cornerstone of CF care and has always been recognized as having a very important role to play. Even from point of diagnosis, when a child may be asymptomatic with their chest, their parents are still taught to engage them in exercise and to get them moving around to make sure they’re maximizing ventilation of the lungs and helping to move any sputum that’s there.

The wide-ranging benefits of exercise on health are continuing to emerge. Throughout my professional career, I have seen people who have come from active families and the fitter they were when they were younger, the better outcome they have later down the line; they’re still functioning at a higher level because they had that training in their younger years.

People are seeing exercise as another way to help control their health, and it is also something that’s more normal to do and that they can do socially with their peers. Someone with CF often has a huge amount of treatment to undertake, a lot of which can be unpleasant, so exercise can be preferable as it is something that can be enjoyable. Every time we see a patient, we ask them about what they are managing to do from an exercise point of view.

What are the main differences between workouts that are specifically designed for CF patients, as opposed to just standard workout routines?

We don’t know exactly how exercise programmes for someone with CF should vary from the normal population; we still need more research to prove this – so what we’re saying is that people with CF should be doing the same amount of cardiovascular exercise and strength and conditioning training as recommended in the national guidelines for the healthy population.

However, because of the factors I mentioned before − that people with CF are very likely to suffer from postural problems, low back pain, stress incontinence and low bone mineral density, etc − physios prescribe exercise programs that make sure we’re addressing these issues before they become a problem, or if they are a problem, that the need is met.

Why is it important to have a personalized exercise routine and what range of exercise routines are available on Pactster?

It is important to have a personalized exercise regime because we are all different; we all have different interests and we all have different needs. There is a lot of pressure on people with CF  to exercise for health benefits, so we must find a way to make it  enjoyable and effective for them. We need to have exercise that is engaging and does not just feel like treatment. It needs to feel like it is going to be fun, as well as meeting the patient’s needs and be easy to integrate into a daily routine.

With a lot of the workouts we have on Pactster, we have really tried to normalize exercise. We know that exercise is medicine, but we want it to be something fun and normal that everybody does. We have used physios and people with CF who are qualified fitness instructors as instructors in the videos; but we film the videos out of the hospital setting, in normal clothes and cover popular exercise disciplines such as yoga, mixed martial arts, pilates, circuits and high-intensity interval training. We are creating more videos to cater for people of different ages and interests, and throughout different stages of the disease.

We are hoping that Pactster will overcome the usual barriers that put people off exercising, like lack of time and money, but that it will also make exercise easier for people who may struggle with low mood, find it hard to get out of the house because they are dependent on oxygen or equipment, have a compromised immune system or who may be too self-conscious to go to the gym. Some people with CF find group classes embarrassing because people may turn and look at them if they start coughing.

Pactster has been designed to overcome these barriers, so that people can gain confidence exercising in their home environments and be reassured that they’re exercising in a safe way, supported by someone who understands their condition.

Zelda and Leah, two CF physios from The Royal Brompton and Harefield NHS Trust

Please give an overview of Pactster and the unique features that you bring to CF physiotherapy?

Pactster offers health-specific exercise videos filmed with specialist instructors alongside community and motivational support. Our exercise videos have been filmed with CF physiotherapists and people with CF who are qualified instructors; and have been approved by the Association of Chartered Physiotherapists in Cystic Fibrosis.

We want people to be inspired by seeing someone with the same condition as them on screen, sharing their knowledge of how to use exercise to take control of their disease.

Currently, in the videos we have on Pactster, the CF instructors are quite highly functioning, but we’re creating new videos that will include people with more advanced disease and people who are pre- or post-transplant, as well as families and kids. Even with more advanced disease, there are still so many fitness role models with CF who who are phenomenal in what they achieve  given the challenges that they face, and who have so much knowledge to share.

Pactster gives the opportunity for people with CF to workout alone or with others in a group setting, this is an important feature as people with CF are unable to meet one another face-to-face due to a risk of cross infection which can significantly impact life expectancy.

These group workouts can be facilitated by a person with CF or by a physio. The good thing about this is that it provides an opportunity for peer support, or if a physio is running the session it may have prevent the need for a hospital visit.

Group workouts are also about motivating and inspiring others as well as providing accountability, enjoyment, and the opportunity for learning. We are currently developing the behaviour change features on Pactster to make it easier to stick to an exercise regime.

Group, online workout has an unlimited number of people who are able to attend

Are there any limitations to the workouts? Do they need specific equipment? I’m guessing these are all open access to all CF patients?

In the UK, our arrangement with the Cystic Fibrosis Trust means that all people with CF, as well as their caregivers and physios can have free access to Pactster. Due to the way CF care is delivered in the UK, it is expected that anyone with CF coming onto the platform would have already been seen by a specialist in a CF centre and that they would have had conversations with their physio about the right amount and type of exercise necessary, as well as how to exercise safely.

It is expected that people come to the platform with some understanding of exercise and then they can participate in what they feel is right for them. Maybe they’ll try something they haven’t tried before because it’s been put right in front of them and it’s easy to do.

Access is free and the equipment that you need to use may vary from one exercise discipline to another. Some will require more hand weights, but you can improvise with a book or a can, for example. There’s also a kettle bell workout on there, if that’s what people are interested in. Generally, most of the exercises require an exercise mat, but not very much equipment after that.

Is it also open access to patients outside of the UK?

There is a monthly subscription of five pounds per month if you’re outside of the UK, but our aim is to try and make it free. As a British person, I believe in the NHS and I believe it is wonderful that healthcare can be free at the point of access.

I would love to make Pactster free for anyone who needs it because we want to reduce as many barriers as possible for someone exercising. Although it’s not much of a financial barrier, making payments is still a barrier for some people. We’ve got people who have signed up from other places around the world, but people are already asking whether there is going to be a similar arrangement in Germany, South Africa, or America and I’d like to find a way to make sure that we can make it free for them.

Will you expand the exercise routines and physiotherapy for other conditions in the future or are you focusing primarily on CF?

I’m predominately a CF physio by background and coincidentally, one of my best friends has CF, so I have a very strong personal attachment to creating this for people with CF and I want to see it working, being a huge success and making a difference.

I do feel that being able to offer specialized exercise videos to someone in their home is incredibly important, as well as being able to provide remote physio support and to connect people who are going through similar conditions. Once we are happy that we have CF working as well as we want it to from a behavior change point of view, as well as videos covering all stages of life from point of diagnosis through to end of life, then yes, we are looking to provide the same service in collaboration with other hospitals or charities for other health conditions.

One example, which we think would be our next step would be working with people with breast cancer as we know exercise is a very important therapeutic intervention for people with breast cancer. Also, at different points of life from diagnosis, pre-mastectomy, post-mastectomy, chemo and radiotherapy, there are lots of barriers to exercise and lots of reasons that exercise needs to be tailored at different points for different needs. The breast cancer population would be another example of a population that we’d like to support using Pactster.

What would you like to see as the future of physiotherapy treatment for CF patients, both in the UK and globally?

I would like physio to be as easily integrated into someone’s life as it can possibly be and every treatment to be as effective as possible. I believe that is about personalizing care and looking at different ways to support people in different settings − at home, in hospital and in the community. I also believe it’s about tailoring our treatment and making it the best we can through creating more of an evidence base and not being afraid to progress with things. Physio is a difficult, laborious task for someone with CF and if we can make it as streamlined, personalized and effective as possible, then that would be awesome.

Ideally, I don’t want people to have to do physio. I want there to be a cure for CF, but so long as that is not the case, then let’s make the therapy the best we possibly can. I’m excited to see where things go from a digital health point of view, because I think there’s potentially lots of different things we can do.

Where can readers find more information?

About Pamela Scarborough

Pamela has been a phyiotherapist in the NHS for 15 years, predominantly working with people with cystic fibrosis. Pamela completed a Master’s looking at yoga for thoracic kyphosis and lower back pain in CF, as well as studying adherence and behaviour change in greater detail. Here, she most enjoyed researching and presenting in those areas, as well as teaching others, sharing new information and approaches on adherence and yoga within the community.

Since then Pamela has been working on Pactster, where she enjoys the creativity of a start-up environment and is excited about the potential of digital health in improving quality and delivery of care. She finds it incredibly satisfying to see people using Pactster and finding it beneficial.

New Promising Results from Phase 3 of Combination Therapy

Findings from a phase 3 trial evaluating the efficacy and safety of tezacaftor in combination with ivacaftor in patients with cystic fibrosis (CF) who were homozygous for the Phe508del mutation were published in the New England Journal of Medicine.

The Phe508del mutation has been known to result in greatly reduced conductance regulator (CFTR) protein activity and a loss of chloride secretion, which can lead to impaction of mucus in the airways, gastrointestinal tract, and exocrine organs, with the potential for severe clinical consequences including gradual loss of lung function, nutritional deficits, pulmonary exacerbations, and respiratory failure. It is the most prevalent CFTR mutation worldwide, and affects approximately 46% of American CF patients.

Previous data has shown Ivacaftor’s association with a rate of progressive decline in lung function that is lower than that in untreated patients. In a phase 2 clinical trial involving patients who were homozygous for the Phe508del mutation or heterozygous for the Phe508del and G551D mutations, when combined with the investigational CFTR corrector tezacaftor, it has exhibited enhanced CFTR function and improved lung function.

In August, just one month removed from Vertex’s announcement of positive datafrom Phase 1 and Phase 2 studies, Rare Disease Report covered the acceptance of applications for the use of the tezacaftor/ivacaftor combination treatment in this patient population by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

The phase 3 trial enrolled a total of 510 patients 12 years and older with CF who were homozygous for the Phe508del CFTR mutation at 91 sites in the U.S., Canada, and Europe from January 30, 2015 to January 20, 2017. Patients were randomly assigned to be administered either tezacaftor and ivacaftor (administered as a fixed-dose combination tablet containing 100 mg of tezacaftor and 150 mg of ivacaftor in the morning and a tablet containing 150 mg of ivacaftor in the evening) combination therapy or placebo for 24 weeks.

In total, 475 patients completed the full 24 weeks of the trial, with 93.6% (n=235) in the tezacaftor-ivacaftor group and 93% (n=240) in the placebo group. While no significant difference in the body mass index (BMI) was experienced between the groups at week 24, the use of the combination therapy led to a significantly greater absolute change from baseline in the predicted forced expiratory volume in 1 second (FEV1) than placebo. Despite advances in standard-of-care therapy, patients with CF continue to lose lung function at a rate of an estimated 1% to 3% per year. This trial exhibited a significant effect of the combination therapy compared to the placebo, as the mean absolute change from baseline in FEV1 through week 24 was 3.4 percentage points in the former, compared to 0.6 in the latter.

The most common adverse events (AEs) among the enrolled patients included infective pulmonary exacerbation, cough, headache, nasopharyngitis, increased sputum production, pyrecia, hemoptysis, oropharyngeal pain, and fatigue. The incidence of AEs was similar in both the group for combination therapy and the placebo group, however, those treated with lumacaftor-ivacaftor in the phase 3 did not experience an increased incidence of respiratory events (33 patients [13.1%] vs. 41 patients [15.9%]).

This improved safety profile of the tezacaftor-ivacaftor combination supports its use in a broad range of patients with CF, and, if approved, the therapy will be the third of Vertex’s drugs approved for CF patients, and the second intended specifically to treat patients with F508del mutations (Orkami [lumacaftor/ivacaftor]).

For original article please visit: http://www.raredr.com/news/phase-3-combination-therapy-cystic-fibrosis?t=physicians

For the published study please visit: http://www.nejm.org/doi/full/10.1056/NEJMoa1709846?query=genetics#t=articleDiscussion