The Personalizing Research Project

I had a sort of epiphany on the trip home from the NACFC .  After 5 years as a "normal person" attending this Conference (the vast majority of attendees are: research scientists from academia, biopharma peeps, clinical care team members, investors, and a hundred or so major donors to the CFF), I have built a number of important connections with scientists working on understanding and testing the CFTR protein, or manipulating the gene somehow to correct for mutations.

My Concerns

Currently, the biopharmaceutical industry is holding the reins as the driving force in drug development and innovation for CF.  Of course, the Cystic Fibrosis Foundation carefully selects which projects to invest in, and does an excellent job of promoting competition to drive prices down...eventually.  This is, in no way, a critique of the actions of the CFF. I hope that everyone that reads my blog understands my position on the actions of the Cystic Fibrosis Foundation.  You might even say I am a "superfan."  I have participated in the Strategic Planning Committee for the Foundation, served on the Patient Engagement Advisory Council, worked as the volunteer chair of the Great Strides walk in Spokane for the last 2 years, attended the CFF sponsored NACFC Conference for the last 5 years, and had their "Adding Tomorrows" logo tattooed on my body.  As much as I love what the CFF is doing, they don't possess the power to control big pharma.

I pledge allegiance...

Also, for the record--there is NO DOUBT that partnering with biopharma has resulted in some huge innovations in the treatment of CF.  Note that my only other tattoo is that beautiful Kalydeco molecule on my left foot, reminding me everyday to "Honor the Gift" we have been given with this Vertex developed miracle.

My observation is that we (patients/families) cannot rely on big pharma to put patients before investors, and the CF Foundation has limited power over things such as cost of any successes resulting from their investments (as we have seen painfully with Kalydeco and Orkambi).  I see a number of issues brewing, that could potentially slow down our progress toward better combinations of potentiators and correctors.  Because I know first hand how life-changing these drugs can be...I think that sucks.  I want to do more than line the pockets of executives and investors...we have the power to enhance the lives of patients and get important people considering the patient as a real part of this equation.  

The FDA and Randomized Placebo Trials

Before I launch into this, I want to say that the FDA has been an amazing partner in CF progress.  The passage of the EXPERRT Act in 2012 gave the agency the flexibility it needed to even consider some of the specialized therapies we are bringing their way.  With consideration to Kalydeco and Orkambi, the FDA provided swift, expert review--bringing the drugs to patient hands in the safest, most expedited manner.  When considering expansion of the Kalydeo label to include the R117h mutation, the FDA listened carefully to patient testimonials, and made the right choice to expand access to these patients in the end.  The FDA has been extremely helpful to us, and has shown that it has the potential and desire to evolve. Right now, we are entering some really murky territory with the FDA.  Traditionally, the FDA has required data from large scale, randomized, placebo controlled trials as a means to gain approval for marketing a drug in the U.S.  How would you feel about the following situation? I would sincerely appreciate anyone who would take the time to leave a comment with their thoughts.

Your child has a residual function mutation, and is benefiting from Kalydeco.  A better potentiator is discovered, but enrolling in the clinical trial for this compound would mean a 1/3 possibility of receiving a placebo for up to 20 weeks.  Would you take the chance of going off Kalydeco, and enroll in the trial anyway?

You are an adult with advanced lung disease who has been taking Orkambi for several months.  The initial few weeks were tough, but you are seeing some benefits, as well as some side effects.  Other companies are racing toward clinical trials with alternatives to Orkambi that present with better in vitro CFTR activation, and potentially safer toxicology report.  A few months ago, a hiccup in insurance coverage caused you to miss several days of Orkambi suddenly, and resulted in a serious (and scary) exacerbation.  If you have the chance of getting assigned a placebo, and going back to non-functional CFTR for a portion of this trial...do you enroll?

You are heterozygous, and want to ensure that the most effective potentiators, correctors, and transcriptional read-through agents get approved to treat your specific combination of CF mutaions, but Vertex has the CF community locked down with their combo for heterozygotes--which is furthest along in development, and will reach the market first.  If the majority of eligible patients are accessing this first option that gets to market, who are we going to test better combos on?

Let me stress again that this is not a direct attack on Vertex--they are simply acting like a business. Vertex just happens to be out in the lead of this race to treat/cure CF, and they are playing the game like any other for-profit pharmaceutical company would. Also imporant to note is that I view the research scientists at Vertex in a much different light than I see the executive leadership.  I have completely mixed emotions--reverence mixed with disgust for Vertex--and the situation is anything but black and white. What I am suggesting, rather, is for enriched patient dialog with the FDA, as we may need to change some rules to see our progress take place in a way that encourages innovation.  I want to make sure that the patient is at the center of the business of curing CF, rather than Vertex alone calling the shots.  As I mentioned before, I would appreciate your comments on these important issues.  

In a discussion I attended at the NACFC, I had a bit of a battle with an FDA reviewer. Please take a look through the slides of his presentation, and consider what is at stake here.  I think this is important to be aware of for everyone with CF--whether you are currently taking a CFTR modifier or not.  

This slide clearly mentions the ethical concerns I have been discussing, but the FDA reviewer seemed to play it off as relatively minor.  He did NOT believe that asking patients to come off of Kalydeco or Orkambi to test potentially superior combos would be a formidable problem to trial enrollment...What do you think?

Dr. Durmowicz was asked a question in regard to the ethics of using placebo controlled trials for upcoming CFTR modulators, and pulling patients off of treatments like Kalydeco or Orkambi, that that may exhibit clearly positive benefits, to test potentially better drug combinations.     

Dr. Durmowicz casually remarked that patients wouldn't mind doing it...in the name of progress.  *This is where I begin feeling extremely agitated.  In my experience with Brady missing doses of Kalydeco due to a stomach bug, and accounts that I have heard from others within the CF community--the "rebound effect" can produce some seriously unpleasant side effects, and in worse cases--potentially dangerous exacerbations.  Not to mention the MENTAL sabotage of finally feeling a dream come true in finally being able to breathe with greater ease, and then being asked to go back to a disease+ state of being.  In my opinion, that is So. Not. Cool.

I worry that the best case scenario is that the trials experience significant delays in enrollment. Worse case scenario is that drugs that could have a meaningful effect can't enroll at all, and the projects can't move forward!  Additionally, I think that FDA regulators are underestimating how hard it can be to come off of CFTR modulators. I have seen and heard from many patients that withdrawal from CFTR modulators can induce an exacerbation, and may produce much less meaningful trial data.   As soon as FDA reviewer Dr. Durmowicz made the remark...steam started pouring out of my ears.  I didn't want to do it, but I couldn't help myself. Something gripped me, and I felt myself rise, and walk to the mic.  I had no choice. I introduced myself as a CF mom with a child taking Kalydeco and explained that I "respectfully disagreed" with his opinion before I gave him a mouthful.  I assured him that no one wants progress more than we do, but our mutual goal is going to be extremely hard to achieve if we can't get patients to enroll in trials they might consider to be unsafe and/or unethical by design. My comments to the FDA regulator drew applause from the audience, and several drug manufacturers approached me afterward to cheer my efforts, and remark that they have the same concerns.  The owner of one company in particular, who is developing an alternative drug for homozygous patients, expressed great excitement over his discovery--but worried about the ability to move forward against a "Vertex monopoly."  As a chemist, I fully understand the need to test these drugs with scientific rigor, to ensure a safe and effective product for the patient consumer...but I also think we are entering uncharted territory with personalizing drugs to alter an individual's cellular biology. If the FDA's main concern is SAFETY, I propose that cycling patients off and on CFTR modulators might have some very unsafe consequences and produce less than meaningful data.  We have a responsibility to at least try to minimize the collateral damage as we continue on this very personalized journey to the perfect CFTR modulator cocktail for each patient.  Please share YOUR EXPERIENCES transitioning on and off CFTR modulators in the comments.  I feel like I have heard a lot of anecdotal remarks, but I am increasingly curious to get a greater body of feedback on this issue. If the FDA doesn't understand our concerns--the responsibility rests on our shoulders to educate them.

In our current environment, we would be naive to rely on for-profit pharmaceutical companies to have our best interests at heart. The same is true for Vertex that is true for other virtually any other pharmaceutical company--the investor is their #1 priority.  As much as I love what companies like Vertex have been able to accomplish in drug development--I am absolutely NOT OK with the $$$ amount placed on my child's health every month. The astronomical price of their innovations has led many countries to be delayed or denied access of Kalydeco and Orkambi.  I am NOT OK when families in several countries around the globe write to me in desperation because their loved ones are being denied access to Kalydeco or Orkambi. Watching someone you love deteriorate before your eyes with CF is torture...watching them deteriorate, knowing there is an existing drug that could alter their lives if you could only access it is a special kind of bitter pill that I wouldn't ask anyone to swallow.  There have been access issues here in the U.S. as well, with one woman in Arkansas waiting over 2 years before getting coverage for Kalydeco.   Many CF patients rely on Medicaid or State programs that have limited budgets, and these are some of the most expensive drugs ever marketed...  This situation sickens me because I know precisely how life changing CFTR modulators can be for some patients--patients like my son Brady.  I want to see MORE CF patients benefiting from these drugs RIGHT NOW, and NEW DRUGS come to market to effectively treat MORE PATIENTS in the future.

What Can I Do?

1) Leave a comment for me to share with the CF Foundation, and the FDA.  

*This blog represents my views alone as a CF Mom, and while I do serve as a volunteer, I am not speaking or writing on behalf of the CFF.  I will, however, be sharing feedback on this issue with them, because I feel they are an important ally for the patient population.

2) Subscribe to the PRP--The Personalize Research Project

At the same time we are helping regulatory guidelines evolve, I've discovered another powerful technique where I feel that the patient community might be able to make significant influence.  In my experiences at the NACFC over the last 5 years, the interactions I've had with scientists have been extremely powerful, and in some cases--altered the course of research.  For me, this year's NACFC was a perfect storm of advocacy, science, emotion, connection, influence, and empowerment.  In the grand scheme of using my specific talents to make the greatest impact in advancing our community toward the cure--I have finally crystallized my focus, my calling, and my goal--to not only personalize the delivery of clinical care for CF patients, and to advocate for a system that meets the needs of patients--but to take it even one step further--and advocate for personalizing the research as well.  When I say personalize, it means two things:

1) Personalize research techniques to effectively test and combine compounds to give the greatest benefit to each individual patient.

• Encourage use of techniques utilizing human airway cells, organoids, nasal epithelia, and animal models developed with specific mutations to obtain the richest data to predict in-vivo clinical correlations.  

• Encourage the use of n-of-1 trial design to allow those with rare mutations or combinations to benefit from CFTR modulator therapies.

2) Personalize the research by making it about the patient.  Personalizing as in, making it personal.

Ultimately, the work done in the lab has an enormous effect on real people...like Brady.

For me, coming face-to-face with research scientists gives me the opportunity to enhance their understanding about why individualizing care options is so important. I do everything I can in these interactions to make them actually care a little bit about Brady.  I want them to think about Brady while they are at work in the lab everyday.  I want them to understand that their work is so incredibly important, and that we appreciate the hell out of it.  I want to influence the person actually holding the test tube, and/or developing the new scientific techniques we will use to cure CF. Even industry drug developers got their start in a University lab somewhere, I want them to understand what it means to live with CF.  Allowing these scientists to understand our struggle in a little more personal way injects their research endeavor with infinitely more meaning (beyond just publishing a paper, or getting another graduate student through their program).  I want to bring the patient/family voice directly to the lab bench.  We DO belong at the table along with academia and industry.  I think this is desperately important in the current drug development environment.

Making the Connection
I get a similar reaction every time I put myself face to face with a research scientist.  First of all, they are surprised that I am there, and that I am so knowledgeable about CF science.  I always thank them for making their career about CFTR science, and do my best to convey the details of how deeply chemistry and the understanding of the CFTR protein has impacted Brady and our family.  Many of them are moved to tears, and write to me later that our meeting was the most meaningful part of the Conference for them, and they ask permission to share the story with their grad students and department.

The Ripple
CF will eventually be cured in a lab somewhere, and I want whoever is behind that cure to care about CF patients a little bit (preferably a lot!)--or at the very least feel some sort of ethical awareness of how their work is impacting actual patients living with this awful disease.  Scientists represent the SOURCE of our progress with understanding and treating CF.  I believe that personalizing the lab work (with the presence of the CF patient/family voice) could serve to infinitely magnify the size of the ripple we are able to make in the research arena.

The Evidence
I have witnessed or been a part of these real instances where a patient or parent interacting with a researcher has had a powerful influence.  For privacy, I have left the names and specifics out of the following scenarios, but these represent REAL EVENTS that I have witnessed at NACFC.  Please share comments if you have experienced the power of the patient/scientist connection.

Case #1) CF Mom who is searching for data on the action of her daughter's rare mutation gets seated next to an important research scientist at dinner. By the end of the night, the scientist realizes he has a cell line in the freezer with the daughter's mutation from a former study he had conducted, and agrees to pull it out and perform a few experiments to see whether Kalydeco might offer some benefit.  The tests show potential for benefit and Mom is able to build a case to obtain off-label coverage.  Mom obtains first script of Kalydeco and is able to document benefits.  Patient has now been able to benefit from Kalydeco for several years before she would have otherwise, and the entire research lab now has a personal connection to CF.

Case #2) CF Mom gets seated next to important research scientist at dinner.  She discusses her son's rare mutation, and her efforts to obtain more knowledge about the potential for current therapies to impact the mutation.  Research scientists invites Mom and her son to visit their lab and donate some cells for them to run tests on.  Mom gets more information about her son's mutation, and the entire lab team now understands the implications of their work as they move forward with their experiments.

Case #3) I attended the NACFC for the first time in 2011 and saw the phase 3 trial data for VX-770.  I was also able to get face-to-face with investigators familiar with the  preliminary data on VX-770 in younger kids. As a result, I understood that future expansion to younger children was undeniably on the horizon--more a matter of time to meet regulatory requirements, than concerns over safety in this younger group. Armed with data, I was able to build a case for off-label coverage of Kalydeco, and access the drug more than 2 years before it is "approved" for my child's age group.  *I am not claiming, by any stretch of the imagination, that attending the NACFC guarantees off-label coverage of anything.  Coverage happens on a case by case basis. I am saying, rather, that detailed knowledge of both the mechanism of action of VX-770, paired with data regarding testing in children guided me to at least TRY to access this drug for my child.  I am saying that if I hadn't attended the NACFC, Brady would have waited 2 more years before starting Kalydeco.  Personally, I wouldn't dream of missing the NACFC, because the knowledge I've gained there has had a significant impact on the real life consequences of the disease for my son.  Period.  

I want to clarify that I am not claiming that interactions with scientists are more important that interactions with the care team.  More accurately, the clinical care team tends to have a better understanding of what CF means, and typically have many "personal" connections to patients and families living with CF, due to their regular interactions in clinic and the hospital. Research scientist often have absolutely zero connection with patients or understand how hard it can be to live with CF. I see interacting with scientists as a sphere of opportunity where we are currently absent, where we have the power to exert a large amount of influence.

So What.

In regard to the goal of personalizing research to offer the most benefits and the least risks to every individual--I encourage you to leave comments on this blog as well as sign up as an advocate on the CF Foundation's website. I have no doubt that issues will arise demanding action from advocates as we move forward. The CF Foundation has amazing policy experts, and they allow us to organize our efforts and make the biggest impact. Every year I come home from the NACFC with deeper insight.  I have witnessed so many important ways that the patient voice is missing, or misunderstood. I think that at this point in history, it is extremely important that we continue to advocate for a system and regulations that support our goals.

We can't afford to stop communicating.  The FDA is evolving right along with medicine, and the CF Foundation has truly developed an exemplary relationship with them over the years. When I go to meetings on Capitol Hill requesting increases in FDA funding--I tell the story of how swiftly and expertly the FDA reviewed the Kalydeco application, and how much that meant to my family.  I want the FDA to be able to do the same for every drug we send their way, and they need proper resources to do it!   In my experience in working with the FDA, the patient voice seems to be deeply regarded, and is a powerful tool (as we saw with the impact of patient testimonials in the expansion of Kalydeco to the R117H mutation).  Many on the voting committee remarked that hearing from the patients themselves made a huge impact on the way they voted.  We need to continue working and communicating deeply with the FDA, as the complexity of our research endeavors demand.  I think there is an enormous potential to work together here, and show the world how curing disease is done!

I will be be exploring some of the techniques available today to test individualized therapies in a future blog.  Researchers see potential in testing on human organoids, nasal epithelial cells,and animal models with specific mutation combinations to bring greater precision to testing, and minimize risks to patients.

Organoid studies provide an exciting opportunity to test the effect of drug combinations on individual patients.  

Lastly, I want to share a dream of mine, that I would like to see materialize--Each time I get the opportunity to connect with a CF scientist, I think to myself--"Man, it would be so awesome to be able to visit their lab, and get to have a conversation with everyone who works there."  If someone were to ask me about my "dream vacation," it would be akin to a world CFTR laboratory tour--so I think I should do just that.  If the goal is to personalize research for CF, getting face-to-face with the person holding the test tube is a good way to start.  I know I need to start talking about this dream, to promote some general awareness, which will hopefully lead me to my next step--financing.  In the meantime, I will be following up with every scientist I had the pleasure of visiting with at the NACFC, and exploring invitations I've already received.  It is time to blow the top off of the idea that patients don't have a place at the research bench.  For truly personalized medicine in a disease community with over 2000 disease causing mutations, I argue that patient voices are the missing "secret sauce" that will help usher in the cure we have all been dreaming of, while simultaneously acting to limit the power of big pharma. *Drop Mic*
**IMPORTANT NOTE. This blog is NOT in any way advising against the infection control guidelines outlined by The Cystic Fibrosis Foundation.  They are based on the latest science, and are there for a reason--safety.  I attended the NACFC Conference as a parent, and believe that meaningful connections can also be made using technology to connect patients with researchers.

Understanding the link between CFTR and Insulin Function--NACFC 2015

Back to business. Time for one quick summary before I head to a special dinner.

Impact of CFTR on Beta cell Function in the Pancreas--presented by Dr. Antoinette Moran.     

                   

I found this talk really interesting and hopeful.  Development of cystic fibrosis related diabetes is extremely common, and the risk increases with age.  CFRD places an additional large treatment burden on patients, and is associated with a number of negative health outcomes.

Abnormal insulin secretion has been shown to begin very early in life—even in children with normal oral glucose tolerance tests.  

This early abnormality led the researcher to question whether the abnormality was present at birth (an intrinsic defect), or developed over time (acquired defect).  Studies using the CF ferret model show that the animals are born with abnormalities—suggesting that this is an issue present at birth. 

With this knowledge in hand, Dr. Moran was curious to examine the link between CFTR function and insulin secretion.  The link between exocrine function of the pancreas (the release of digestive enzymes) and the presence of functional CFTR is fairly well understood.  The same basic mechanism of mucous dehydration and mucous plugging that causes scarring in the lungs, also leads to ductal blockages in the pancreas--thereby impairing digestive enzyme secretion.  The connection between CFTR and endocrine function (insulin secretion), is still being uncovered.  The question Dr. Moran posed in this study was whether restoration of CFTR function with a drug like Kalydeco might be able to improve insulin secretion, and prevent or delay the onset of CFRD. 

First, Dr. Moran set out to determine whether CFTR was, in fact, present in the insulin secreting beta cells in the pancreas.  Evidence is not 100% conclusive, but highly suggests that CFTR is in fact present in these cells.  

The role of chloride transport (by way of CFTR), has never been included in the classic model of insulin secretion.  

Dr. Moran believes that there is sufficient evidence to update this model to include the role of the chloride channel.

Ultimately, this study examined the insulin secretion of a small group of patients before, and after one month of therapy with Ivacaftor.

  

As shown in the bar graph, treatment with Ivacaftor produced a significant improvement in insulin secretion.  This is "tantalizing evidence" that correction of CFTR with a modulator drug like Kalydeco has the potential to delay or prevent the onset of CFRD.  Dr. Moran noted that while Type II Diabetes develops differently than CFRD, there may be potential to augment insulin secretion for this group as well with amplification of CFTR function.

While there is certainly more work to be done in this area of study, I walked out of the room with the hope that Kalydeco may help prevent CFRD for my son Brady and many others.

NACFC 2015--Details from Day 1

This morning, the action began at 10 a.m. with a host of workshops.  Because there are always multiple interesting talks happening at the same time, Brock and I decided to divide and conquer to take in the most information.  Here are the most interesting nuggets from my morning.

I was anxious to hear the results of the European Gene Therapy Trials at the NACFC last year, but the UK team backed out last minute in order to complete their data collection process.  I was able to see their data earlier this year in a videotaped presentation by Dr. Alton, but this was the first time that the trial results have really been shared at a meeting like this, with the professional CF community at large. 

A Randomized, Double-blind, Placebo-controlled Trial of Repeated Nebulization of Non-viral CFTR Gene Therapy in Patients with Cystic Fibrosis.  Presented by Dr. Eric Alton

While research in the U.S. has been focused on the “small molecule” approach to treating CF, scientists in the UK have poured a tremendous amount of time and energy into gene therapy.  The UK CF Gene Consortium has been working for years on this project, and has encountered considerable obstacles along the way.  The most formidable challenge has been identification of an effective vector to transmit genes inside the lung cells of CF patients.  Many viral vectors were tested and abandoned due to the high inflammatory response they elicited (infection by virus is one way to breach the cell wall and gain access to the DNA held inside, but was found to cause too much collateral inflammatory damage to be an effective candidate).  Ultimately, a lipid (fat) vector was chosen to perform a phase 2b placebo controlled trial in humans.  Trial participants were asked to nebulize a gene therapy solution once a month (approximately 40 minutes to complete treatment). Ultimately, the study showed statistically significant improvements in FEV1.  

Patients exhibiting the most severe lung disease showed the least benefit from this treatment, and Dr. Alton hypothesizes that fibrosis and mucous barriers associated with more severe lung disease could be obstructing the interaction with lung tissue--preventing the transfer of the healthy gene.

Dr. Alton believes that this study, while modest in benefit, provides proof of concept that gene therapy should be further developed as a tool for treating CF.  The next steps would involve pushing the boundaries to see if further benefit might be obtained with higher dosages.  Also, if gene therapy is able to activate a small amount of CFTR in the lungs, there is the possibility that the chloride transport by this small amount of CFTR could be enhanced with the addition of a small molecule potentiator such as Kalydeco.

While gene therapy is an exciting concept, it is something that researchers have been working on for decades--basically since the discovery of the CF gene in 1989.  The treatment benefits seen in the trial were modest, but represent the greatest success to date using this approach.  Dr. Alton seems determined to continue down this road, but I have doubts... Personally, I think that the gene-editing or mRNA editing techniques (such as CRISPR-cas9 that we will hear about later in the conference) hold more promise as a way of actually changing an individual's genetic expression.  Just my opinion.  I was hoping for much better data after so many years of development.

Mesenchymal Stem Cell LL-37 in Cystic Fibrosis.  Presented by Tracey Bonfield

Human mesenchymal stem cells (hMSCs) come from bone marrow, and are able to differentiate and develop into many different cell types in the body.  There is no need to suppress the immune system to utilize hMSCs, making them an attractive candidate for therapy development.  

For this study, the CF mouse model was used to test how hMSCs might affect CF lungs.  The mice were infected with Pseudomonas aeruginosa and then treated with hMSCs.  The mice were followed for 10 days.  The data collected suggests that hMSCs exhibit both anti-inflammatory as well as anti-microbial properties.  The rate of Pa growth in the mice was decreased, and combination with an antibiotic treatment produced a synergistic effect (augmented the potency of the antibiotic).  

While this work is preliminary, this trial in mice shows measurable benefit, and further studies with hMSCs to treat CF lungs will be coming our way in the future.

Hormone Fluctuations Correlate with Respiratory Symptoms in Patients with Cystic Fibrosis. Presented by Raksha Jain.

Existing data has suggested that women with CF have worse health outcomes than men. Women demonstrate earlier colonization with respiratory pathogens and an increased exacerbation rate near ovulation.  This study examined the role that sex hormones play in CF.

This was an observational study where hormones were measured throughout the course of the menstrual cycle.  Inflammatory markers were measured, and patient reported data was collected as well.  Additionally, data was collected for women with CF who were asked to cycle on and off birth control pills--which function as an estrogen inhibitor.

The data they collected basically suggests that higher estrogen levels correlate to worse respiratory symptoms.  This was shown with an increased rate of exacerbation during the follicular phase of the menstrual cycle (when estrogen is highest).  It was also shown that suppression of estrogen with oral contraceptives trends toward reduced exacerbations, and should potentially be examined as a therapeutic option (this was a very small study, so these findings are suggestive rather than conclusive). 

The take-away message--further study is warranted to determine if oral birth control pills may represent a way to improve the health status of women with CF through the suppression of estrogen.  

These 3 studies represent a tiny fraction of the discussions I saw today (I didn't even make it to my afternoon notes yet--but I have to be able to stay awake tomorrow)!  

After the morning session concluded at NACFC, Brock and I dashed over to the Volunteer Engagement Conference at the Renaissance to snag some lunch and connect with other CF families. I also had the privilege to speak about advocacy alongside Mary Dwight and Abi Green from the CFF, and my CFF National Advocacy co-chair Melissa Shiffman (who filmed an awesome advocacy video that I will be able to share when the link is made available).  Nothing inspires me to preach advocacy like spending my morning listening to the amazing scientific progress that is happening RIGHT NOW. 

I made it on and off stage without falling on my face--success!

 It makes me sick to my stomach to think about struggling with access barriers when we have so many wonderful opportunities speeding through the drug development pipeline.  I feel strongly that advocacy needs to be a priority for anyone who cares about the future of someone with CF, because progress means absolutely nothing in the absence of access.  I love analogies, and in my mind, we--the CF community-- are all piled in this homespun machine, moving closer and closer to the finish line (curing CF).  

Inside our machine are multiple interlocking gears that must mesh and spin simultaneously.  The awareness gear interacts with, and helps power fundraising--which leads to scientific investments--which ultimately bring new drugs and therapies into existence.  

The engine of our machine is humming along at breakneck speed!  BUT, there is another crucial juncture we must attend to, where all our inner gears interact with the axle (the ADVOCACY gear). This is the gear responsible for physically spinning the wheels to propel us forward.  If we fail to make that interaction with our system, our inner gears will be left to simply spin...while our machine goes NOWHERE.

You can imagine that it wouldn't take very long for those spinning wheels (and impatient families) to build up some intense heat.    

I believe that we MUST advocate to avoid a situation where the inner gears of our machine are held back by a structure that isn't ready/willing/capable to help us move those wheels closer to our goal. Imagine for a second that advocates HADN'T recently been successful at passing the Ensuring Access to Clinical Trials Act (EACT), and we had the money and science to move forward with exciting clinical trials--but barriers to trial participation stood in our way and slowed us down... I know that I would get hot under the collar in a hurry.  Knowing the passionately CF community the way that I do, I think we run the risk of some serious engine trouble in that situation. We can't let that happen.  

Advocate regularly to avoid engine trouble!

  

With that, I will close for tonight.  Tomorrow is another full day of workshops and symposium sessions.  Plus, I need to be at my best for lunch with Dr. Beall, and dinner with some of the best scientists in the world.  Stay tuned--we are just getting started!

Welcome to NACFC 2015

The North American Cystic Fibrosis Conference brings together thousands of brilliant scientists and clinicians to discuss their research, and ways to improve care in CF clinic.  As a CF Mom with a chemistry degree, I am drawn like a magnet. The conference is draining--physically, intellectually, and emotionally.  I subsist mostly on coffee, wine, and protein bars and don't sleep much.  I am a zombie by the time I get home, and my head spins for weeks on all the new information I have learned, and people I have met...and I wouldn't miss it for the world!  I even attended in 2012 on crutches after knee surgery.  It would take a natural disaster of some kind to keep me away.

This year, there is a new event piggybacked on the NACFC called the “Volunteer Engagement Conference (VEC), which will bring volunteers from the West together for scientific updates and Foundation news.  My husband and I arrived in Phoenix yesterday afternoon and attended a beautiful welcome reception for volunteers and Foundation leadership at the home of Robert and Carole Griego.  It is always really special to me when I get the chance to spend time with other CF families.  I’m excited to speak at the VEC this afternoon about the importance of prioritizing advocacy as we move through an evolving healthcare system toward personalized treatments for cystic fibrosis.   

As you can imagine, there is a mountain of new scientific information to digest every year.  I have every expectation that this year is going to BLOW MY MIND.  This morning, my plan is to attend the workshop entitled “New Advances in CF Animal Models.”  I’m going to send my husband Brock to the “Novel Targets and Outcome Measures” workshop to take notes and pictures.  I hope to have another post later today about what we learned.  After lunch, I will be speaking at the Volunteer Engagement Conference alongside Mary Dwight and Abi Green from the Foundation, and my National Advocacy co-chair Melissa Shiffman.

This afternoon, I will be attending a symposium-- “Partnering with Patients and Families to Promote Healthy Lifestyles,” which will feature discussion about exercise, alternative therapies, anxiety management, and wellness through diet.  After that, we will attend the first Plenary session—“Personalized Medicine,” where several speakers will discuss the process of tailoring the care and drug regimen to the needs/mutations of each individual patient.   

It is such an awesome feeling to sit in the huge room where the Plenary sessions are held--surrounded by 4000+ professionals who all care deeply about curing CF.  It is like being transported to another planet where, fortunately, I speak the same language as the natives.  

I’m a little nervous about my knee brace/high heel combo, so hopefully I don’t take a nose dive down the escalator! Barring disaster, I will be blogging to the best of my ability again this year.  Stay tuned for updates!

Come to the Table

I hate politics.  I really do.  I haven't taken a political science course since Freshman year.  All the partisan bickering and lack of action on important issues is annoying and frustrating.  It often seems like campaigning for the next election is all many of our politicians care about, and I can’t stand to watch live television during an election cycle because it makes me want to throw things at my TV…

So why in the world would I travel from northern Idaho to Washington D.C., suit up, and walk 8 miles in heels navigating the maze of offices on Capitol Hill?  Why do I feel absolutely compelled to inject myself into that political world and lob my heart onto the lovely mahogany desks of my elected representatives?   Because I am a mother of a child with cystic fibrosis.  For me, this is not political—this is personal. 

Brady is 7 years old, and LEGO obsessed!  Sometimes it feels like my whole world looks like this!

Whether we like it or not, our healthcare system is evolving, and every year lawmakers are voting on legislation and budgets that will directly impact families and patients living with cystic fibrosis.  The Cystic Fibrosis Foundation understands this, and has been working to establish a presence on Capitol Hill for many years.  On March 19, over 120 CF advocates, representing 38 states participated in 273 meetings in the CF Foundation’s “March on the Hill” event.    This is an opportunity for CF experts (YOU!) to come to the table, and educate elected officials on what it means to live with cystic fibrosis.  It is our opportunity to bring the unique needs of our community to their attention, and explain how budget appropriations and certain pieces of legislation can impact those living with CF.  Not convinced this is for you?  Let me outline the ways that CF advocacy has touched my own life.

July 26th 2007, Brady came into this world.  He was the first baby in Idaho to be picked up on the newborn screening program.  That test was added to the newborn panel in Idaho the same week that Brady was born.  After a positive screen came back, we performed genetic testing and he was diagnosed with CF before he was 3 weeks old.  We were able to intervene immediately, and begin treatment with enzymes, airway clearance, CF vitamins, and other medicines that would help him grow and thrive.  He didn’t have to become terribly ill and suffer potentially irreversible damage before we knew something was wrong.  Obviously, the diagnosis was traumatic (especially in the throes of post-partum sleep deprivation and fluctuating hormones), but the benefits of early intervention are well studied, and we are eternally grateful that we had the opportunity to begin helping Brady fight this disease as soon as we could.  The newborn screening program is up and running in all 50 states, which is awesome!   Newborn screening exists today because CF advocates worked for years on Capitol Hill to get it added to the newborn panel in each and every state. 

When Brady was a baby, I learned that the Idaho Legislature was proposing legislation to cut a co-pay assistance program for adult patients with CF. The budget for this program was a mere drop in the bucket ($200,000 total annual budget), but a game-changer for adults needing assistance in Idaho.  We already know that 1 in 4 CF patients sometimes skip doses of medication, or go without some prescriptions all together because of cost issues.  Cutting this program would mean that many adults with CF in my state would lose the ability to get some of the drugs that they needed to manage their disease.  It made $1000+ co-pays a monthly reality for many adult patients in Idaho.  It caused severe anxiety and depression for some of those adults already struggling with advanced disease.  It caused some adults who had previously been able to work part-time to lose/quit their jobs and become fully dependent on Medicaid or SSI for coverage of their life-sustaining drugs.  It sucked (especially when I learned that the Idaho Legislature was creating a new “slush fund” with a $200,000 annual budget to pay lawyer fees when legislators found themselves in lawsuits that same year).  Everything about it reeked.  Though it wouldn’t affect Brady directly (the program was for adults only), he was on a similar state program for children, and I realized that lawmakers were going to be making decision about his access to care and drugs.  I realized that many of the people making those decisions didn’t even know what cystic fibrosis was.  I realized that unless I spoke up—they may never know.  (Insert long rant of obscene language, and imagine me banging my head against a brick wall).

A newspaper article from our battle with the Idaho Legislature.

If you are reading this blog, you might already know that my son Brady has been taking Kalydeco for over 3 years, and that it has changed our lives.  But did you know that the technology that led to the discovery of Kalydeco—“high-throughput screening,” was developed by the National Institutes of Health?  Did you know that targeting a genetic mutation for correction wouldn’t be possible without the NIH first mapping the human genome?  Without the basic science that has helped us unravel the mysteries of our DNA, we wouldn’t even be able to DREAM of the kinds of “genetic modifying” drugs like Kalydeco that are being crafted today.  Just to be clear—the CF Foundation funds nearly 100% of medical research for CF.  The National Institutes of Health does NOT give a single dollar to the CF Foundation, or “orphan” (rare) disease research.  They DO, however, fund basic science projects that enhance our understanding of genetics.  They DO develop new technologies that could accelerate drug discovery for all diseases.  They DO fund generalized research projects that may eventually be applicable to CF.  The importance of funding the NIH has ALWAYS been a priority for CF advocates.

Take a look at our drug development pipeline.  It is jam packed with hopes and dreams.  Hopefully, many of the drugs in clinical trials right now will be applying to the FDA for review in the coming years.  When new drug applications are submitted, it is vitally important that the FDA has the resources they need to expertly and swiftly review those applications.  The CF Foundation has worked for many years to build a relationship with the FDA, and enhance their understanding of our projects and goals.  Kalydeco was granted “priority review” status by the FDA, which served to expedite the approval process, and was given one of the fastest reviews in history (less than 3 months from submission to approval!)  Awesome! As you know, the  quicker these miracles can get into patient hands…the better. 

I hope I've made my case that CF advocacy is not about politics after all.  I honestly believe that working to help shape our system is the most important way to ensure progress toward the cure and protect Brady's access to care and medicine.  After attending the NACFC for the last 4 years, I am amazed and inspired by the science coming through the pipeline.  We don't want roadblocks on the path to the cure. It is extremely important to educate our lawmakers on the unique needs of the cystic fibrosis community if we want a system that helps individuals and families with CF thrive... and YOU are the best experts in the world! It is much better to proactively troubleshoot problems that we foresee as we move toward the cure, than sit back and complain about a system that doesn't work for us when the damage is already done.  CF advocacy is about coming to the table and giving input about the policies that are shaping the future of healthcare,  With that in mind, I want to share more about the specific action items that March on the Hill advocates met with lawmakers about last week. 

1) Co-sponsorship of the Ensuring Access to Clinical Trials Act of 2015 (EACT) S139 H.R. 209

This legislation removes the sunset provision (expiration date) from the "Improving Access to Clinical Trials Act" (IACT), which was passed in 2010.  IACT allows patients with CF and other rare diseases to receive up to $2,000 in compensation for participating in clinical trials without that compensation counting toward their income eligibility limits for SSI and Medicaid.  Without this legislation, patients that we NEED to be able to participate in clinical trials, may not be able to, out of fear of losing their vital benefits.  The Cystic Fibrosis Foundation is planning to fund 18 clinical trials next year--requiring 2500 patients to participate.  When you consider the various exclusion criteria for those trials, and the fact that we only have about 30,000 CF patients nationwide--it is extremely important to remove this barrier to participation.  IACT is set to expire in October.  Advocates are trying to get EACT passed before this happens!  This legislation costs a negligible amount of money, but is extremely important to ensure speedy and full enrollment of new clinical trials.  EACT applies to all rare diseases, not just CF.  Rare diseases impact nearly 1 in 10 Americans.  According to the NIH, there are over 7,000 rare diseases affecting between 25-30 million people across the country.  Rare disease researchers face real challenges recruiting enough patients to perform trials, and current treatment options are often very limited.  Back in 2010, IACT received bipartisan support, and has allowed us to progress quickly forward with trial enrollment for the last 5 years.  We really aren't asking for anything new at all with EACT--simply to remove the 5 year expiration date, and allow the law to remain permanent.  Last week at March on the Hill, CF advocates from 38 states attended 273 meetings--and asking for support of this legislation was a priority in every one.  EACT also has good bipartisan support...but we need to push it across the finish line here and now.  You can help by taking action through the CF Foundation's advocacy page.  Click, "Take Action Now," then "Tell Congress to Protect Access to Clinical Trials," and follow the prompts.  You can personalize the pre-written letter a bit with your CF connection, and send it directly to your representatives!  This takes about 1 minute, and is a really effective way to let lawmakers hear your voice!  It would be especially helpful if constituents from Texas could help us put some pressure on Senator Ted Cruz.  I mean, the CF Foundation is funding the research.  All we want is the opportunity to test our new amazing science in clinical trials! Is that too much to ask?  NO!

2) Support funding for the NIH and FDA.  

CF advocates are working to boost funding to the NIH this year and are asking lawmakers to approve a budget where the NIH receives at least $32 billion dollars in 2016. NIH funding has been flat since 2002 (which translates to a DECREASE in funding each year when you take inflation into account).   That means that the NIH has been able to fund fewer and fewer interesting projects that are seeking funding each year.  What is slipping through our fingers in those missed opportunities?  What if one of those basic science projects might lead us to a cure for CF?  It requires you to take a big step back and take a look at the big picture, but we NEED to see basic science research take a bigger priority in our government’s budget appropriations.  Globally, America is falling behind, and it is only going to get worse unless we change this trend.  Investing in medical science is an investment in the FUTURE of this country, and the future of our loved ones with CF.  Last week, CF advocates explained why NIH funding is important to the CF community on Capitol Hill, and asked them to sign the "Dear Colleage" letter circulating in both the House and the Senate to show their support of the $32 billion dollar budget.  You can "Take Action Now," then click "Protect our Progress Toward a Cure for CF," and follow the prompts.  Once again--a minute of your time could make a big impact for families living with CF.  

The FDA worked smoothly and quickly for Kalydeco.  Why are we making FDA funding an issue?  The medical research community is soon going to be asking the FDA to consider a huge number of new drugs in different ways than it ever has before.  Historically, to be considered a candidate for approval, the FDA has required long term trials with a large pool of patients.  Obviously, these criteria aren’t going to work for mutation specific CF drug trials.  As a rare disease, and with new therapies targeted at specific genetic mutations, there may only be a few hundred (or less) “qualified” patients that even exist worldwide!  It would be impossible to enroll huge numbers of patients for individualized genetic treatments for an already rare disease.  In 2012, CF advocates played an integral role in the passage of the EXPERRT Act.  As part of this legislation, a new “breakthrough” designation was created for drugs that treat life-threatening diseases, for which there is no alternative.  Drugs that are granted breakthrough status, are given a faster review schedule than ever before.  The legislation also enables the FDA to bring in disease experts to consult on trials that don’t fit the old school criteria.   Passage of the EXPERRT act was a big victory for the CF community, but we aren’t satisfied yet.  While CF is blazing the trail for this type of drug design, an increasing number of disease communities are uncovering genetic correlations of their own, and developing targeted therapies.  Personalized treatment is the future of medicine for everything from CF to cancer and beyond.  The FDA is going to need a larger staff to effectively review the growing number of new individualized drug applications coming their way in the near future.  What a shame it would be to see amazing new drugs bogged down in delays over a simple lack of time and personnel to perform safe and prompt reviews.  We want our future new drug applications to be considered with the same prompt expertise we saw with the Kalydeco approval.  Bottom line is that the FDA is going to need more money to function like we need it to in the very near future. If you sent the "Protect our Progress Toward a Cure for CF" email, you are already done!  Robust funding for both the NIH and FDA are included in that request!

3) Join CF Caucus in the House of Representatives.  

The CF Caucus is sort of like a "club" that House Representatives can join to signify their support for the CF community.  Follow the link to see if the people who represent you are members! Membership in the caucus raises awareness about CF, and issues that will impact patients and families living with the disease.  We try to grow membership in this Caucus every year. Currently, there is no CF Caucus in the Senate.  We don't have a specific action item in our CFF advocacy toolkit for this, but you are always free to email your own elected State officials and invite them to join the CF Caucus in the House (or find a great supportive Senator to START a caucus in the Senate!).  

New issues come up all the time that could affect the CF community.  To me, advocacy is about putting face on this disease, and letting our lawmakers know that their votes affect us as people.  We are not just a number in a budget.  Their votes mean something to us.  We are the Mothers, Fathers, Grandparents, Sons, Daughters, Brothers, Sisters, Aunts, Uncles, Friends, and Patients dealing with this disease.  As despicable as politics can seem at times...our lawmakers are actually just people.  Most of them have families, and can imagine what dealing with CF must be like.  I try to relate to them on a personal level to help them understand.  When you are sitting face to face with them, the intimidation fades away, and it becomes apparent that they are actually very much like us. I encourage you to explore CF advocacy efforts in your state, and contact publicpolicy@cff.org with questions.  

As a mother who has been lucky enough to see what a bright future new therapies like Kalydeco might hold for our CF community, I am determined to remove system barriers that might slow us down. I want EVERY patient and family to have a miracle like Kalydeco! I am honored and excited to serve as the CF Foundation's new National Advocacy Co-Chair with an awesome lady, Melissa Shiffman from NY.  Melissa is an adult with CF, who is the mother of two beautiful children.  As we are moving toward the goal of curing CF, there WILL BE OBSTACLES that require advocates to speak up.  I believe with all my heart that if we want a system that works for us...If we want coverage that meets our needs...if we want to be fed...we must first come to the table!  My life has been so touched by CF advocates.  I feel like "Thank you" is a huge understatement.  Besides, once you get bit by the advocacy bug, you can never quit!  It is so empowering!  Get involved in advocacy today and help protect the future for everyone with CF. Please "Sign up" to receive the CF Foundation's advocacy newsletter, and action alerts!  How about taking 30 seconds to advocate for CF patients RIGHT NOW by sending a tweet to Senator Ted Cruz in Texas asking him to support EACT?!  Something like...

"The ‪#‎CysticFibrosis‬ community needs access to clinical trials, @SenTedCruz Pass S. 139!! ‪#‎cfAdvocacy‬ @CF_Foundation"

Thank you wonderful people!  

With my RAD new Co-Chair Melissa Shiffman on Capitol Hill last week!

Chatting up CF advocacy at Sacred Heart's Family Ed day a few weeks ago. Do I ever shut-up?  NOPE!
And neither should you!