10 November 2016

8+ Things I Learned at NACFC 2016

Here is a recap of NACFC 2016.  Fair warning, this post is looooong.  But it's chocked full of great slides, access to the plenaries and to links for further information about the newest in CF research shared at NACFC.   

Although, this is a much abbreviated version of all that went on a NACFC this year, to give it some organization, I've broken this blog post into: 

8+ Things I Learned At The 2016 
North American Cystic Fibrosis Conference 
this year

1.) The CFTR Modulator Pipeline is diversified and robust

This slide shows the demographics of the CF population in the modulator area, a breakdown by molecular theratype.  There are 5% of people with CF who have two stop codon mutations.  On this slide, Bennett is in the dark yellow.  Ultimately, Bennett is part of 12% of those with CF who have one stop codon mutation (621+1G>T) and a non-stop codon mutation (F508del).

This slide shows the historic effort being extended worldwide to make sure the CF community meets its goal for a cure for all.  If you look close, you can see the sponsor's name, drug name, the drug class and the current research and development stage the drug is in.

This slide shows where targeted therapy is headed next.

I love this slide because it shows how much farther we still have to go.  As more CF genotypes are treated with better modulators at younger ages, the health of the CF population will shift dramatically.

Although with modulators we expect a smaller proportion of individuals with CF will have need for "downstream" therapies, there will still be a need for these therapies.  This slide shows the anticipated changes in CF population size, health and treatments.

But we know that modulators will ultimately not likely be able to provide a cure for CF for the CFF is continuing to work on new options.

2.) Gene-editing is bringing hope to those with CF who don't benefit from CFTR modulators.
CF researchers are asking: how do we attain a therapy targeting CFTR when not all patients have the same CFTR defect?  

What do we do with those Class 1 and Class 5 mutations...and the 5% of patients that have both copies of the Stop Codon mutations in them? Since there is no CFTR and therefore CFTR is not getting to the surface, CFTR modulators aren't going to work. 

There is an new technique that is being researched that the CFF hopes will help those who don't benefit from CFTR modulators.  It's called gene-editing.

Although I can't even begin to explain gene editing, this slide is still image from a video shown at NACFC about CF and gene editing.  Watch the fascinating video starting at 1:15:02 here:

This slide shows the greatest challenges of gene editing today.  The CFF has partnered with Editas and CRSPR Therapeutics to find a way to make this work.  With gene editing is there are 190,000 base pairs.  The CFF can't focus on them all.  So, the CFF is focusing on those mutations that do not currently look to benefit from CFTR modulators.

Beyond gene-editing, another technique being researched is manipulating the RNA to address X-mutations (stop codon mutations).

Here are specific programs working on the premature truncation and X mutations that affect the 5% of people with CF who do not benefit from modulators.

3.) There are 10,000 more CF adults now than there were in 1986.  

The demographics are changing in CF.  More adults are college graduates, students/employed and married or living together than ever before.

In 30 years, median predicted survival has seen a 12 year improvement.  Although this slide does not show it, the median age of death was in the 3rd decade of death in the 1980's but we've seen only a 5 year improvement in that area over the last 30 years.  However, it's worth noting that all of this data reflects the era before modulators (before Kalydeco and Orkambi).  Everyone expects this data to only get better in the coming years.

 This is a new metric that is going to appear in the Patient Registry Report this year is "life expectancy by age."  This graph shows that if you've achieved a certain age (represented by the yellow), what are your calculated additional years of life expected (represented by the white).  But, again, this data is pre-modulators.  It is expected that those on Kalydeco and Orkambi would see even higher numbers.

4.) CFTR genotypes (genetics) affect phenotypes (symptoms) but how much depends on the factor being considered.

There is a growing understanding of mutations and how they affect the disease.  But, it turns out, it's very complicated.

There tends to be three areas of factors that impact CF: CFTR genotype, genetic modifiers (other genes besides CFTR) and environmental factors/random events.

Pancreatic sufficiency is almost completely dependent on CFTR genotype while intestinal obstruction risk and age/onset of diabetes is almost completely dependent on genetic modifiers.  Studies show environmental care/random factors can have some impact on airway obstruction, body mass index and pseudomonas aeruginosa infections.

It would be very nice if we could determine survival based on known genetic defect.  But this slide reminds us that that is not possible considering the myriad of factors that go in to determining one's health.

5.) Early life nutrition has significant impact on pulmonary system. 

This left side of the slide shows that when examined in pre-2001 data, children with the lowest lung function also had the lowest weight-for-age.  Even if you adjust for signs of lung disease, this data didn't change, in fact, it got stronger.  It turns out, what determine's one having more lung decline is having small lungs.  Recently, similar data (on the right side) was evaluated to see if this data had changed.  Clearly, it has not.

Conversely, data also shows that if you improve your nutritional status, your lung function goes up dramatically.

As Wayne Morgan, MD said when he shared these slides: "a child's job is to build big lungs, healthy lungs.  If you are not growing well, if you are nutritionally behind, your body is sacrificing lung growth to presumably grow the brain, it does hurt the lung."

Growing strong lungs is imperative.  "Because we know that when they are grown, they begin to decline," said Wayne Morgan, MD, Chief of Pediatric Pulmonary Medicine at the University of Arizona during his talk. When we look at the decline in lung function with age, we see that preteen to adult (9-18 years) is when the greatest decline in lung function occurs.  This slide also shows what's associated with lung function decline.  What is interesting here is that a predictor of more rapid decline is someone whose FEV1 is predicted to be 100 or more.  Why would that be?  (see Things I Learning at NACFC #5:)

6.) Sicker patients receive more treatments.  But that needs to change.

This slide shows that, on average, at 3 months, 75% of CF patients have gotten back to their baseline lung function after an exacerbation.  At 6 months, 81% of CFpatients have gotten back to their baseline.  At the end of a year, 85% of people with CF have been able to get back to their normal lung function.  However, pulmonary exacerbations can have long-term implications as 15% of patients fail to recover 90% of their baseline FEV1 within a year.  That's 1 in every 7 people with CF don't recover their baseline.  That can be 4-5 years of decline related to one event.  Dr. Morgan explained we have a lot more to learn in this area - how to prevent them and treat them.  There are several studies going on right now learning more, including understanding exacerbations in children.

The interesting thing is having an exacerbation predicts an exacerbation.  Compared to those who have never a exacerbation and lose just 1% of lung function per year, those who have had an exacerbation lose 1.8% of lung function per year  ."If you are having an exacerbation, you are likely to have though the disease becomes accelerated.  Exacerbations eat away at lung function," says Dr. Morgan.

This slide shows a 2013 analysis of those who had low lung function, about 50% of them received IV treatment (with a high percentage receiving oral treatment) for, on average, 20% of lung function loss.  But this data shows that the healthier patients, the patients with the higher baseline lung function, the less likely they were to be treated.  Dr. Morgan explains, "so, if you compare the highest deciles, the highest lung function patients to the lowest, the odds of the healthiest being treated, the odds ration is .15, almost nonexistent.  And that's completely illogical.  Because if you have 100% lung function, and you lost 20% of it, then you've lost a lot more lung function than someone who is 50% and lost 20%. And also, in a disease that we know accelerates, where exacerbations predict exacerbations, we could be missing a chance to stop that if we are not treating healthy patients...we appear not to be treating people as aggressively as we should."

While more patients are being treated today than ten years ago, the same trend is evident. 

7.) Efficiency of treatment (clinical trials) does not equal effectiveness (real world).

It's important to know that just because a medication looks like it works really well in a trial, it may not work as well in the real world for every patient.  Some reasons this is possible include the fact that trials often exclude the sickest patients who  benefit, patients are often given more careful followup while in the trial, there is more standardization of management in a trial and patients in trials are often more adherent to their treatments than those who are not in trials.

8.) People with CF and their families can now drive the research agenda (more on this to come in a follow up blog post).

Although the patient registry has been around for decades, for the first time ever, the CFF is looking for people with CF and their families to give feedback on what *they* want to know more about with regard to cystic fibrosis.

Between now and the end of January, people with CF and their families (as well as other CF community members, including clinicians) can go here: to submit their research questions.  Any question about anything related to CF is appreciated but the kinds of questions are hoping for most are those such as:

* Do people with CF in different regions of the US have different infection rates and health outcomes?
* Do Hispanics with CF have the same expected survival rate as non-Hispanics?
* Do all people with CF eligible for transplant get a referral?  If not, are those not referred different from those who are referred?
* What are the factors that make it more likely that people with CF will recover lung function lost during an exacerbation?

I am personally co-leading this initiative with a great co-leader, David, and a fantastic team of people with CF and parents of kids with CF, who are working alongside the CF Foundation to develop better ways to help people with CF and their families engage in CF research.

The InsightCF Registry Research Project is different than clinical trials because it uses observational research collected through the patient registry of almost every person with CF who is seen at a CF Care Center within the US.  I look forward to hearing what people with CF and their families want to know more about and how the Patient Registry can help answer our questions!


Watch the 1st 2016 NACFC Plenary Session here: 

(To download these slides, go here:

Watch the 2nd 2016 NACFC Plenary Session here:
(To download these slides, go here:

Watch the 3rd 2016 NACFC Plenary Session here:
(To download these slides, go here:


I wasn't able to go to everything that NACFC offered as it's offerings are way more vast time I had or brain power to understand.  So, I was delighted to find a really fantastic resource that has outlined a lot of the new info from NACFC.  Check out these links from Cystic Fibrosis News Today (as well, scroll down to see blog posts from my CF Mama-friend Rebecca):

Colonoscopy Colon Cancer Screening Recommendations are being made for adults with CF
"[Researchers suggest] that split preps from a colonoscopy are better than single, large-volume preps." Read more here:

Exercises Targeting Trunk Muscles May Improve CF Urinary Incontinence
"As patients’ life expectancy significantly increases, other body systems also become affected by the disease, such as the the neuromuscular and musculoskeletal systems...children with cystic fibrosis are particularly prone to develop urinary incontinence.Read more here:

Kalydeco Seen to Improve Insulin Secretion in Patients with CF-related Diabetes"Results suggest that Kalydeco treatment affects beta-cells function and improves their secretion capacity. However, another possible mechanism is Kalydeco having an indirect action on other pathways that improve CF outcomes, including an increase in insulin secretion, without affecting beta-cell secretion capacity." Read more here:

Relizorb Increases Fat Absorption in Patients with Cystic Fibrosis Receiving Enteral Nutrition
"RELiZORB use during the administration of enteral nutrition among these patients was safe and well-tolerated. Patients reported a decrease in the frequency and severity of gastrointestinal symptoms, particularly stool-related symptoms, associated with deficient fat absorption. Also, more patients were able to preserve their appetite and were able to eat breakfast." Read more here:

Airway Microbiome Research Key To Understanding CF Disease Mechanism
""culture-independent” approaches suggest that CF airways may be infected by many more bacterial species than thought." Read more here:

CF Women Face Lack in Research in Birth Control Options Risks Unplanned Pregnancy
"No studies have been performed exploring if and how Orkambi impacts the use of non-oral contraceptives...There are also no official guidelines for contraceptive use in women with cystic fibrosis, leaving physicians to take into account disease-specific factors, such as diabetes and bone health, when selecting suitable birth control options." Read more here:

Next Generation CFTR Correctors Show Improved Activity Repair Defects
"Results support the ongoing clinical evaluation of VX-152 and VX-440 combined with first-generation CFTR correctors and Kalydeco in CF patients who carry the mutation F508del." Read more here:

New Database Could Identify CF Patient Variables, Outcomes After Lung Transplant
A "new database is a potential tool for optimizing the timing of referral for transplant and for identifying all variables to effectively predict the risk of waitlist and post-transplant morbidity and mortality for in CF patients." Read more here:

Severe Cystic Fibrosis CF Lung Disease Not Obstacle Appropriate Lung Transplant
"Our results demonstrate that the very advanced end-stage CF patients who are highly likely to die without transplant have comparable overall survival rates to more stable end-stage CF patients." Read more here:

Talk Details Challenges in CF Vaccine Development
"Infections with mucoid P. aeruginosa...remain the major initiator and driver of lung function decline in CF, and vaccination against this microbe is still a research priority." Read more here:

Many Eligible CF Patients Miss Out on Orkambi Treatment, Study Shows
"Clinicians may be slower to recommend [Orkambi) therapy compared to historical precedent with [Kalydeco] monotherapy in a different group of patients.” Read more here:

CF Patients Benefit from Home Tai Chi Training Using Video Calls, Face-to-Face Sessions
"As internet-based interventions are both safe and economic, researchers suggest that group sessions over the internet should be the next logical step toward financially sound and effective therapies for cystic fibrosis patients." Read more here:

Getting the Upper Hand on Mucus in Cystic Fibrosis
"Abnormal mucus clearance in patients with cystic fibrosis (CF) may be improved with specific treatments, but despite intense research on the subject, there are many unanswered questions about how atypical mucus contributes to the disease and how to best improve the problem." Read more here:

Potential Treatments for Biofilm Infections and Intestinal Inflammation Show Promise in Early Studies
"Promising results of preclinical studies evaluating the effectiveness of SYGN113 to treat bacterial biofilms in the lungs of patients with cystic fibrosis (CF), and of SYGN303 to treat the gastrointestinal consequences of the disease, were presented." Read more here:

Loss of Hydration in Airways Associated with Early CF in Preschoolers
"A team of researchers investigated which factors are associated, from an early stage, to airway alterations in patients with CF... [study] results suggest that airway dehydration is an important therapeutic target in young children with CF."

CFTR Potentiators, Correctors Explored Rare Mutations in Cystic Fibrosis
"Research is currently ongoing to evaluate which of the rarer mutations can be targeted with combinations of CFTR potentiators and correctors."

Close Gastroenterologist Monitoring of Patient Enteral Tube Feeding Urged by CFF

Small Study Shows Perceptions Raise Barriers to Palliative Care Use In Cystic Fibrosis: 
"Although CF can be a severe condition that reduces life expectancy among patients, there is no consensus among patients or healthcare professionals about how to incorporate the principles of palliative care into CF management." Read more here:

NACFC Notes From Day 1 - Rebecca's Blog

Slides from Day 1 Plenary - Rebecca's Blog

Genome Editing - Rebecca's Blog

Slides from Day 2 Plenary - Rebecca's Blog

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